Trial Outcomes & Findings for Selumetinib in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine (NCT NCT00559949)

Last Updated: 2017-01-30

Results Overview

ORR: Complete Response (CR) and Partial Response (PR) evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. A conservative estimate of the response rate of the best-studied agent in this disease, doxorubicin, is approximately 5%. Therefore, investigators will assume that selumetinib (AZD6244, NSC 741078) would be worth further pursuit if the response rate (CR+PR) were at least 20%.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

39 participants

Primary outcome timeframe

Up to 2 years

Results posted on

2017-01-30

Participant Flow

Between December 11, 2007 and June 30, 2009, 39 patients were enrolled at 5 cancer centers in the United States and one cancer center in Canada.

Participant milestones

Participant milestones
Measure	Arm I Patients receive oral selumetinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression. Laboratory Biomarker Analysis: Correlative studies Selumetinib: Selumetinib was administered orally as a free base suspension at a dose of 100 mg twice daily for 28-day cycles. Those participants experiencing Common Terminology Criteria for Adverse Events (CTCAE) v3.0 grade 3 toxicity or worse had their dose reduced to 50 mg twice daily and then to 50 mg once daily, if necessary.
Overall Study STARTED	39
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I Patients receive oral selumetinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression. Laboratory Biomarker Analysis: Correlative studies Selumetinib: Selumetinib was administered orally as a free base suspension at a dose of 100 mg twice daily for 28-day cycles. Those participants experiencing Common Terminology Criteria for Adverse Events (CTCAE) v3.0 grade 3 toxicity or worse had their dose reduced to 50 mg twice daily and then to 50 mg once daily, if necessary.
Overall Study Progressive Disease during cycle 1	1
Overall Study Adverse Event	1
Overall Study Withdrawal by Subject	4
Overall Study No disease evaluation per protocol	1

Baseline Characteristics

Selumetinib in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I n=39 Participants Patients receive oral selumetinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression. Laboratory Biomarker Analysis: Correlative studies Selumetinib: Selumetinib was administered orally as a free base suspension at a dose of 100 mg twice daily for 28-day cycles. Those participants experiencing Common Terminology Criteria for Adverse Events (CTCAE) v3.0 grade 3 toxicity or worse had their dose reduced to 50 mg twice daily and then to 50 mg once daily, if necessary.
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	21 Participants n=99 Participants
Age, Categorical >=65 years	18 Participants n=99 Participants
Age, Continuous	64 years n=99 Participants
Gender Female	13 Participants n=99 Participants
Gender Male	26 Participants n=99 Participants
Region of Enrollment Canada	5 participants n=99 Participants
Region of Enrollment United States	34 participants n=99 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Population: All evaluable participants

Outcome measures

Outcome measures
Measure	All Evaluable Participants n=32 Participants Participants evaluable according to protocol guidelines at time of analysis.
Objective Response Rate (ORR)	1 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: All participants

PFS is defined as the duration of time from start of treatment to time of progression or death. Progression evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive Disease (PD): 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm. Secondary end points include toxicity, progression free survival, and overall survival. Due to the small sample size and absence of high quality historic data for this disease, these analyses were planned to be mostly exploratory and descriptive in nature.

Outcome measures

Outcome measures
Measure	All Evaluable Participants n=39 Participants Participants evaluable according to protocol guidelines at time of analysis.
Median Progression-Free Survival (PFS)	32 weeks Interval 8.4 to 56.0

SECONDARY outcome

Timeframe: Up to 2 years

Population: All participants

Number of participants with related adverse events, per category and Grade category. Toxicity assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Outcome measures

Outcome measures
Measure	All Evaluable Participants n=39 Participants Participants evaluable according to protocol guidelines at time of analysis.
Occurrence of Treatment Related Adverse Events Grade 1-2 - Rash	23 adverse events
Occurrence of Treatment Related Adverse Events Grade 1-2 - Diarrhea	17 adverse events
Occurrence of Treatment Related Adverse Events Grade 1-2 - Fatigue	16 adverse events
Occurrence of Treatment Related Adverse Events Grade 1-2 - Peripheral edema	12 adverse events
Occurrence of Treatment Related Adverse Events Grade 1-2 - Elevated liver enzymes	9 adverse events
Occurrence of Treatment Related Adverse Events Grade 1-2 - Electrolyte abnormalities	7 adverse events
Occurrence of Treatment Related Adverse Events Grade 1-2 - Nausea/vomiting	7 adverse events
Occurrence of Treatment Related Adverse Events Grade 1-2 - Stomatitis	6 adverse events
Occurrence of Treatment Related Adverse Events Grade 1-2 - Dyspnea	5 adverse events
Occurrence of Treatment Related Adverse Events Grade 3-4 - Rash	7 adverse events
Occurrence of Treatment Related Adverse Events Grade 3-4 - Diarrhea	2 adverse events
Occurrence of Treatment Related Adverse Events Grade 3-4 - Fatigue	3 adverse events
Occurrence of Treatment Related Adverse Events Grade 3-4 - Peripheral edema	2 adverse events
Occurrence of Treatment Related Adverse Events Grade 3-4 - Elevated liver enzymes	0 adverse events
Occurrence of Treatment Related Adverse Events Grade 3-4 - Electrolyte abnormalities	0 adverse events
Occurrence of Treatment Related Adverse Events Grade 3-4 - Nausea/vomiting	0 adverse events
Occurrence of Treatment Related Adverse Events Grade 3-4 - Stomatitis	1 adverse events
Occurrence of Treatment Related Adverse Events Grade 3-4 - Dyspnea	0 adverse events

SECONDARY outcome

Timeframe: Up to 2 years

Population: All participants

Overall Survival using the Kaplan-Meier method with associated confidence intervals. OS analysis was intended to be mostly exploratory and descriptive in nature.

Outcome measures

Outcome measures
Measure	All Evaluable Participants n=39 Participants Participants evaluable according to protocol guidelines at time of analysis.
Overall Survival (OS)	NA months Interval 1.0 to Due to the long survival time in this disease, actuarial overall survival cannot be estimated during this timeframe. High end of range has not been met.

Adverse Events

All Participants

Serious events: 7 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	All Participants n=39 participants at risk All participants on study.
Cardiac disorders Atrial fibrillation	2.6% 1/39 • Number of events 1 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
General disorders Death NOS	5.1% 2/39 • Number of events 2 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Metabolism and nutrition disorders Dehydration	2.6% 1/39 • Number of events 1 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Nervous system disorders Memory impairment	2.6% 1/39 • Number of events 1 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Nervous system disorders Syncope	2.6% 1/39 • Number of events 1 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Psychiatric disorders Confusion	2.6% 1/39 • Number of events 1 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.6% 1/39 • Number of events 1 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Vascular disorders Hypotension	2.6% 1/39 • Number of events 1 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.

Other adverse events

Other adverse events
Measure	All Participants n=39 participants at risk All participants on study.
Blood and lymphatic system disorders Anemia	25.6% 10/39 • Number of events 21 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Eye disorders Blurred vision	7.7% 3/39 • Number of events 4 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Eye disorders Extraocular muscle paresis	7.7% 3/39 • Number of events 3 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Eye disorders Eye disorders - Other, specify	5.1% 2/39 • Number of events 2 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Gastrointestinal disorders Abdominal pain	7.7% 3/39 • Number of events 3 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Gastrointestinal disorders Constipation	12.8% 5/39 • Number of events 5 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Gastrointestinal disorders Diarrhea	53.8% 21/39 • Number of events 34 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Gastrointestinal disorders Dry mouth	15.4% 6/39 • Number of events 6 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Gastrointestinal disorders Dysphagia	7.7% 3/39 • Number of events 4 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Gastrointestinal disorders Flatulence	7.7% 3/39 • Number of events 3 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	5.1% 2/39 • Number of events 2 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Gastrointestinal disorders Mucositis oral	15.4% 6/39 • Number of events 8 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Gastrointestinal disorders Nausea	23.1% 9/39 • Number of events 15 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Gastrointestinal disorders Vomiting	12.8% 5/39 • Number of events 6 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
General disorders Fatigue	61.5% 24/39 • Number of events 37 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
General disorders Edema face	17.9% 7/39 • Number of events 13 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
General disorders Edema limbs	35.9% 14/39 • Number of events 22 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
General disorders Fever	7.7% 3/39 • Number of events 4 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
General disorders Flu like symptoms	5.1% 2/39 • Number of events 5 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
General disorders Pain	15.4% 6/39 • Number of events 6 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Infections and infestations Bronchial infection	5.1% 2/39 • Number of events 2 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Infections and infestations Infections and infestations - Other, specify	12.8% 5/39 • Number of events 6 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Infections and infestations Sinusitis	5.1% 2/39 • Number of events 2 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Infections and infestations Upper respiratory infection	5.1% 2/39 • Number of events 2 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Investigations Alanine aminotransferase increased	20.5% 8/39 • Number of events 12 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Investigations Alkaline phosphatase increased	7.7% 3/39 • Number of events 4 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Investigations Aspartate aminotransferase increased	15.4% 6/39 • Number of events 10 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Investigations Creatinine increased	5.1% 2/39 • Number of events 9 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Investigations Lymphocyte count decreased	15.4% 6/39 • Number of events 14 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Investigations Neutrophil count decreased	10.3% 4/39 • Number of events 4 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Investigations Platelet count decreased	7.7% 3/39 • Number of events 4 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Investigations Weight gain	10.3% 4/39 • Number of events 4 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Investigations Weight loss	5.1% 2/39 • Number of events 2 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Investigations White blood cell decreased	10.3% 4/39 • Number of events 7 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Metabolism and nutrition disorders Anorexia	17.9% 7/39 • Number of events 10 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Metabolism and nutrition disorders Hyperglycemia	28.2% 11/39 • Number of events 24 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Metabolism and nutrition disorders Hyperkalemia	12.8% 5/39 • Number of events 9 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Metabolism and nutrition disorders Hypoalbuminemia	17.9% 7/39 • Number of events 19 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Metabolism and nutrition disorders Hypocalcemia	15.4% 6/39 • Number of events 8 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Metabolism and nutrition disorders Hypomagnesemia	7.7% 3/39 • Number of events 4 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Metabolism and nutrition disorders Hypophosphatemia	7.7% 3/39 • Number of events 3 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Musculoskeletal and connective tissue disorders Back pain	5.1% 2/39 • Number of events 2 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	7.7% 3/39 • Number of events 5 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	7.7% 3/39 • Number of events 3 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Nervous system disorders Dizziness	7.7% 3/39 • Number of events 4 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Nervous system disorders Dysgeusia	12.8% 5/39 • Number of events 6 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Nervous system disorders Headache	10.3% 4/39 • Number of events 7 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Nervous system disorders Peripheral motor neuropathy	5.1% 2/39 • Number of events 2 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Nervous system disorders Peripheral sensory neuropathy	12.8% 5/39 • Number of events 8 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Psychiatric disorders Depression	5.1% 2/39 • Number of events 2 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	5.1% 2/39 • Number of events 2 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Respiratory, thoracic and mediastinal disorders Cough	10.3% 4/39 • Number of events 5 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	23.1% 9/39 • Number of events 10 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Respiratory, thoracic and mediastinal disorders Pneumonitis	7.7% 3/39 • Number of events 3 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	10.3% 4/39 • Number of events 4 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Respiratory, thoracic and mediastinal disorders Voice alteration	5.1% 2/39 • Number of events 2 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Skin and subcutaneous tissue disorders Alopecia	7.7% 3/39 • Number of events 3 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Skin and subcutaneous tissue disorders Dry skin	10.3% 4/39 • Number of events 4 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	7.7% 3/39 • Number of events 5 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Skin and subcutaneous tissue disorders Rash acneiform	30.8% 12/39 • Number of events 27 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Skin and subcutaneous tissue disorders Rash maculo-papular	38.5% 15/39 • Number of events 33 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	12.8% 5/39 • Number of events 9 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.
Vascular disorders Thromboembolic event	5.1% 2/39 • Number of events 4 • From first on treatment date to 30 days post last off treatment date, 7 years, 8 months. All participants were evaluated for adverse events.

Additional Information

Dr. David Neil Hayes

UNC Lineberger Comprehensive Cancer Center

Phone: 919-966-3786

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60