Trial Outcomes & Findings for Saracatinib and Paclitaxel in Platinum-resistant Ovarian Cancer (NCT NCT01196741)

NCT ID: NCT01196741

Last Updated: 2015-05-05

Results Overview

Where a patient's disease is not measurable by RECIST v1.1, response may be based on GCIG CA125 criteria plus symptoms. The 6 month progression-free survival rate will be calculated by the trial statistician during the final analysis.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

107 participants

Primary outcome timeframe

Using RECIST v1.1 at baseline; at Week 7 or 8 of each chemotherapy cycle; and 3 monthly during follow up. CA125 response will be assessed at baseline, weeks 1, 3 and 6 of each chemotherapy cycle, and at every follow up visit.

Results posted on

2015-05-05

Participant Flow

Participant milestones

Participant milestones
Measure	Saracatinib Plus Weekly Paclitaxel Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Saracatinib: Saracatinib 175 mg PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression	Placebo Plus Weekly Paclitaxel Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Matched placebo: Matched placebo PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression
Overall Study STARTED	71	36
Overall Study COMPLETED	11	8
Overall Study NOT COMPLETED	60	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Saracatinib Plus Weekly Paclitaxel Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Saracatinib: Saracatinib 175 mg PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression	Placebo Plus Weekly Paclitaxel Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Matched placebo: Matched placebo PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression
Overall Study Disease progression	34	14
Overall Study Adverse Event	10	6
Overall Study Serious Adverse Event	3	1
Overall Study Dose limiting Adverse Event	2	1
Overall Study Withdrawal by Subject	3	0
Overall Study Other reason	3	3
Overall Study Other	3	2
Overall Study Protocol Violation	2	1

Baseline Characteristics

Saracatinib and Paclitaxel in Platinum-resistant Ovarian Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Saracatinib Plus Weekly Paclitaxel n=71 Participants Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Saracatinib: Saracatinib 175 mg PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression	Placebo Plus Weekly Paclitaxel n=36 Participants Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Matched placebo: Matched placebo PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression	Total n=107 Participants Total of all reporting groups
Age, Continuous	62.8 years n=99 Participants	66.9 years n=107 Participants	63.4 years n=206 Participants
Sex: Female, Male Female	71 Participants n=99 Participants	36 Participants n=107 Participants	107 Participants n=206 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United Kingdom	71 participants n=99 Participants	36 participants n=107 Participants	107 participants n=206 Participants
Cancer Antigen 125 (CA125)	628 U/mL n=99 Participants	667 U/mL n=107 Participants	648 U/mL n=206 Participants
Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0	23 participants n=99 Participants	15 participants n=107 Participants	38 participants n=206 Participants
Eastern Cooperative Oncology Group Performance Status (ECOG PS) 1	45 participants n=99 Participants	20 participants n=107 Participants	65 participants n=206 Participants
Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2	3 participants n=99 Participants	1 participants n=107 Participants	4 participants n=206 Participants
International Federation of Gynecology and Obstetrics(FIGO) Ovarian Cancer Staging at diagnosis I	6 participants n=99 Participants	2 participants n=107 Participants	8 participants n=206 Participants
International Federation of Gynecology and Obstetrics(FIGO) Ovarian Cancer Staging at diagnosis II	5 participants n=99 Participants	1 participants n=107 Participants	6 participants n=206 Participants
International Federation of Gynecology and Obstetrics(FIGO) Ovarian Cancer Staging at diagnosis III	45 participants n=99 Participants	31 participants n=107 Participants	76 participants n=206 Participants
International Federation of Gynecology and Obstetrics(FIGO) Ovarian Cancer Staging at diagnosis IV	11 participants n=99 Participants	1 participants n=107 Participants	12 participants n=206 Participants
International Federation of Gynecology and Obstetrics(FIGO) Ovarian Cancer Staging at diagnosis Unknown	4 participants n=99 Participants	1 participants n=107 Participants	5 participants n=206 Participants
Histological subtype High grade serous	46 participants n=99 Participants	27 participants n=107 Participants	73 participants n=206 Participants
Histological subtype Low grade serous	4 participants n=99 Participants	2 participants n=107 Participants	6 participants n=206 Participants
Histological subtype Clear cell	6 participants n=99 Participants	1 participants n=107 Participants	7 participants n=206 Participants
Histological subtype Grade 3 endometrioid	2 participants n=99 Participants	2 participants n=107 Participants	4 participants n=206 Participants
Histological subtype Grade 1/2 endometrioid	3 participants n=99 Participants	1 participants n=107 Participants	4 participants n=206 Participants
Histological subtype Undifferentiated	7 participants n=99 Participants	2 participants n=107 Participants	9 participants n=206 Participants
Histological subtype Unknown	3 participants n=99 Participants	1 participants n=107 Participants	4 participants n=206 Participants
Prior Surgery Yes	67 participants n=99 Participants	31 participants n=107 Participants	98 participants n=206 Participants
Prior Surgery No	2 participants n=99 Participants	5 participants n=107 Participants	7 participants n=206 Participants
Prior Surgery Unknown	2 participants n=99 Participants	0 participants n=107 Participants	2 participants n=206 Participants
Prior Taxane Interval <6 months	15 participants n=99 Participants	8 participants n=107 Participants	23 participants n=206 Participants
Prior Taxane Interval >=6 months/None	56 participants n=99 Participants	28 participants n=107 Participants	84 participants n=206 Participants
Number of lines of Prior Chemotherapy 1-2	43 participants n=99 Participants	19 participants n=107 Participants	62 participants n=206 Participants
Number of lines of Prior Chemotherapy >2	26 participants n=99 Participants	17 participants n=107 Participants	43 participants n=206 Participants
Number of lines of Prior Chemotherapy Unknown	2 participants n=99 Participants	0 participants n=107 Participants	2 participants n=206 Participants
Number of lines of Prior Chemotherapy	2.0 lines of chemotherapy n=99 Participants	2.0 lines of chemotherapy n=107 Participants	2.0 lines of chemotherapy n=206 Participants

PRIMARY outcome

Timeframe: Using RECIST v1.1 at baseline; at Week 7 or 8 of each chemotherapy cycle; and 3 monthly during follow up. CA125 response will be assessed at baseline, weeks 1, 3 and 6 of each chemotherapy cycle, and at every follow up visit.

Outcome measures

Outcome measures
Measure	Saracatinib Plus Weekly Paclitaxel n=69 Participants Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Saracatinib: Saracatinib 175 mg PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression	Placebo Plus Weekly Paclitaxel n=35 Participants Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Matched placebo: Matched placebo PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression
6 Month Progression-free Survival Rate (PFS) (Based on Combined Response Evaluation Criteria In Solid Tumours (RECIST) v1.1 +/- Gynecologic Cancer Intergroup (GCIG) CA125 Criteria)	29 percentage of participants Interval 22.0 to 37.0	34 percentage of participants Interval 23.0 to 46.0

SECONDARY outcome

Timeframe: First saracatinib/placebo dose until death, assessed up to 36 months

Outcome measures

Outcome measures
Measure	Saracatinib Plus Weekly Paclitaxel n=69 Participants Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Saracatinib: Saracatinib 175 mg PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression	Placebo Plus Weekly Paclitaxel n=35 Participants Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Matched placebo: Matched placebo PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression
Overall Survival	10.1 months Interval 8.3 to 16.2	12.3 months Interval 11.0 to 14.4

SECONDARY outcome

Where a patient's disease is not measurable by RECIST v1.1, response may be based on GCIG CA125 criteria plus symptoms.

Outcome measures

Outcome measures
Measure	Saracatinib Plus Weekly Paclitaxel n=69 Participants Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Saracatinib: Saracatinib 175 mg PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression	Placebo Plus Weekly Paclitaxel n=35 Participants Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Matched placebo: Matched placebo PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression
Objective Response Rate Based on Investigator Assessment Based on RECIST v1.1 +/- GCIG CA125 Criteria	29 percentage of participants	43 percentage of participants

SECONDARY outcome

Where a patient's disease is not measurable by RECIST v1.1, response may be based on GCIG CA125 criteria plus symptoms. Duration of Response will be calculated by the trial statistician during the final analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Patients will fill in FACT-O questionnaires at the following timepoints: baseline; Weeks 1, 3 and 6 of every chemotherapy cycle; at every follow up visit

The TOI value for each patient is derived at each timepoint by calculating the sum of 3 subscales: Physical Well-Being (PWB), Functional Well-Being (FWB), Additional Concerns. Each subscale score is derived from questions with 4 answers (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). In each subscale reversals are performed and the individual question scores added together. This value is then multiplied by the number of questions within the subscale, and divided by the number of questions answered to derive a subscale score. The higher each subscale score, the better the QoL. PWB 7 questions, lower values=better QoL. FWB 7 questions, higher values=better QoL. Additional concerns 11 questions (higher values in 6 questions=better QoL; higher values in 5 questions=worse QoL) The TOI is reported for each arm based on the average TOI score of each patient calculated across the outcome measure time frame. The higher the TOI, the better the QoL.

Outcome measures

Outcome measures
Measure	Saracatinib Plus Weekly Paclitaxel n=69 Participants Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Saracatinib: Saracatinib 175 mg PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression	Placebo Plus Weekly Paclitaxel n=35 Participants Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Matched placebo: Matched placebo PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression
Quality of Life: Trial Outcome Index (TOI) Based on FACT-O	66.89 units on a scale Standard Error 1.89	73.10 units on a scale Standard Error 2.56

SECONDARY outcome

Where a patient's disease is not measurable by RECIST v1.1, response may be based on GCIG CA125 criteria plus symptoms. Time To Progression will be calculated by the trial statistician during the final analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first saracatinib/placebo dose to first documented progression and/or death, assessed up to 36 months

Outcome measures

Outcome measures
Measure	Saracatinib Plus Weekly Paclitaxel n=69 Participants Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Saracatinib: Saracatinib 175 mg PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression	Placebo Plus Weekly Paclitaxel n=35 Participants Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Matched placebo: Matched placebo PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression
Median PFS	4.7 months Interval 3.6 to 5.5	5.3 months Interval 3.6 to 7.2

Adverse Events

Saracatinib Plus Weekly Paclitaxel

Serious events: 40 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo Plus Weekly Paclitaxel

Serious events: 18 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Saracatinib Plus Weekly Paclitaxel n=69 participants at risk Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Saracatinib: Saracatinib 175 mg PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression	Placebo Plus Weekly Paclitaxel n=35 participants at risk Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Matched placebo: Matched placebo PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression
Blood and lymphatic system disorders Febrile neutropenia	4.3% 3/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	0.00% 0/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Gastrointestinal disorders Vomiting	5.8% 4/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	8.6% 3/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Gastrointestinal disorders Abdominal pain	5.8% 4/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	0.00% 0/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Gastrointestinal disorders Diarrhea	4.3% 3/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	5.7% 2/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
General disorders Fever	4.3% 3/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	2.9% 1/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Gastrointestinal disorders Small intestinal obstruction	4.3% 3/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	2.9% 1/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0

Additional Information

Prof Iain McNeish, Professor of Gynaecological Oncology

University of Glasgow

Phone: +44 (0)141 330 3968

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Participating sites may not publish trial results without prior written consent from the Trial Management Group
Publication restrictions are in place

Restriction type: OTHER

Measure	Saracatinib Plus Weekly Paclitaxel n=69 participants at risk Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Saracatinib: Saracatinib 175 mg PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression	Placebo Plus Weekly Paclitaxel n=35 participants at risk Paclitaxel: Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator. Matched placebo: Matched placebo PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression
Blood and lymphatic system disorders Anemia	1.4% 1/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	0.00% 0/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Blood and lymphatic system disorders Febrile neutropenia	4.3% 3/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	0.00% 0/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Investigations Neutrophil count decreased	2.9% 2/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	0.00% 0/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Gastrointestinal disorders Vomiting	5.8% 4/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	8.6% 3/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Gastrointestinal disorders Abdominal pain	5.8% 4/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	0.00% 0/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Gastrointestinal disorders Diarrhea	4.3% 3/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	5.7% 2/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
General disorders Fever	4.3% 3/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	2.9% 1/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Gastrointestinal disorders Small intestinal obstruction	4.3% 3/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	2.9% 1/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Respiratory, thoracic and mediastinal disorders Dyspnea	2.9% 2/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	2.9% 1/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	2.9% 1/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Infections and infestations Catheter related infection	0.00% 0/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	2.9% 1/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
General disorders Fatigue	2.9% 2/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	2.9% 1/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Gastrointestinal disorders Abdominal distension	0.00% 0/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	2.9% 1/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Metabolism and nutrition disorders Dehydration	2.9% 2/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	0.00% 0/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	0.00% 0/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	2.9% 1/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Skin and subcutaneous tissue disorders Rash maculo-papular	2.9% 2/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	2.9% 1/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Infections and infestations Skin infection	0.00% 0/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	2.9% 1/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Gastrointestinal disorders Nausea	1.4% 1/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	2.9% 1/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Infections and infestations Urinary tract infection	1.4% 1/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	2.9% 1/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Metabolism and nutrition disorders Anorexia	1.4% 1/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	0.00% 0/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Cardiac disorders Ventricular arrthymia	0.00% 0/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	2.9% 1/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Investigations Creatinine increased	1.4% 1/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	0.00% 0/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Infections and infestations Endocarditis infective	1.4% 1/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	0.00% 0/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Infections and infestations Fungal chest infection	1.4% 1/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	0.00% 0/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Infections and infestations Lung infection	1.4% 1/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	0.00% 0/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Cardiac disorders Myocardial infarction	1.4% 1/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	0.00% 0/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.4% 1/69 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	0.00% 0/35 • From trial consent to 30 days after last administration of saracatinib/placebo. According to Common Terminology Criteria for Adverse Events (CTCAE) v4.0