Trial Outcomes & Findings for Trametinib or Combination Chemotherapy in Treating Patients With Refractory or Advanced Biliary or Gallbladder Cancer or That Cannot Be Removed by Surgery (NCT NCT02042443)

NCT ID: NCT02042443

Last Updated: 2017-09-12

Results Overview

From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

53 participants

Primary outcome timeframe

Up to 2 years from registration

Results posted on

2017-09-12

Participant Flow

Participant milestones

Participant milestones
Measure	Trametinib Patients receive trametinib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Chemotherapy Patients receive either A) leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46-48 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity or B) capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	27	26
Overall Study Eligible and Analyzable	24	20
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	27	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Trametinib Patients receive trametinib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Chemotherapy Patients receive either A) leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46-48 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity or B) capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study Adverse Event	2	1
Overall Study Withdrawal by Subject	0	1
Overall Study Progression	21	17
Overall Study not protocol specified	1	1
Overall Study Not eligible/not analyzable	3	6

Baseline Characteristics

Trametinib or Combination Chemotherapy in Treating Patients With Refractory or Advanced Biliary or Gallbladder Cancer or That Cannot Be Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Trametinib n=24 Participants Patients receive trametinib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Chemotherapy n=20 Participants Patients receive either A) leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46-48 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity or B) capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Total n=44 Participants Total of all reporting groups
Age, Continuous	63 years n=99 Participants	61 years n=107 Participants	62 years n=206 Participants
Sex: Female, Male Female	18 Participants n=99 Participants	11 Participants n=107 Participants	29 Participants n=206 Participants
Sex: Female, Male Male	6 Participants n=99 Participants	9 Participants n=107 Participants	15 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=99 Participants	1 Participants n=107 Participants	4 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=99 Participants	19 Participants n=107 Participants	39 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	2 Participants n=99 Participants	3 Participants n=107 Participants	5 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	5 Participants n=99 Participants	2 Participants n=107 Participants	7 Participants n=206 Participants
Race (NIH/OMB) White	16 Participants n=99 Participants	15 Participants n=107 Participants	31 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Planned Chemotherapy 5FU/LV	7 Participants n=99 Participants	6 Participants n=107 Participants	13 Participants n=206 Participants
Planned Chemotherapy Capecitabine	17 Participants n=99 Participants	14 Participants n=107 Participants	31 Participants n=206 Participants
Site of Disease Cholangiocarcinoma	19 Participants n=99 Participants	15 Participants n=107 Participants	34 Participants n=206 Participants
Site of Disease Gall bladder	5 Participants n=99 Participants	5 Participants n=107 Participants	10 Participants n=206 Participants

PRIMARY outcome

Timeframe: Up to 2 years from registration

Population: Eligible and analyzable patients.

From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Outcome measures

Outcome measures
Measure	Trametinib n=24 Participants Patients receive trametinib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Chemotherapy n=20 Participants Patients receive either A) leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46-48 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity or B) capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Survival	4.3 months Interval 3.1 to 5.1	7.9 months Interval 3.2 to 14.6

SECONDARY outcome

Timeframe: Up to 2 years

Population: Eligible patients who received any treatment and were assessed for adverse events are included in this summary. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.

Adverse event reporting followed the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.

Outcome measures

Outcome measures
Measure	Trametinib n=23 Participants Patients receive trametinib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Chemotherapy n=20 Participants Patients receive either A) leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46-48 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity or B) capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Alanine aminotransferase increased	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hepatobiliary disorders - Other, specify	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Mucositis oral	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Thromboembolic event	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Anemia	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Ascites	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Aspartate aminotransferase increased	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Blood bilirubin increased	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Colitis	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Fatigue	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Gastric ulcer	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Gastritis	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Gastrointestinal disorders - Other, specify	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Generalized muscle weakness	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hyponatremia	1 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Infections and infestations - Other, specify	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Neutrophil count decreased	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Pain in extremity	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Palmar-plantar erythrodysesthesia syndrome	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Sepsis	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Urinary tract infection	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Vomiting	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 2 years from registration

Population: All eligible and analyzable patients with measurable disease.

Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.

Outcome measures

Outcome measures
Measure	Trametinib n=24 Participants Patients receive trametinib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Chemotherapy n=20 Participants Patients receive either A) leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46-48 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity or B) capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Objective Response Rate Symptomatic Deterioration	1 Participants	1 Participants
Objective Response Rate Partial Response	0 Participants	2 Participants
Objective Response Rate Unconfirmed Partial Response	2 Participants	0 Participants
Objective Response Rate Stable/No Response	2 Participants	9 Participants
Objective Response Rate Increasing Disease	19 Participants	8 Participants

SECONDARY outcome

Timeframe: Up to 2 years from registration

Population: Eligible and analyzable patients.

From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.

Outcome measures

Outcome measures
Measure	Trametinib n=24 Participants Patients receive trametinib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Chemotherapy n=20 Participants Patients receive either A) leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46-48 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity or B) capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Progression-free Survival	1.3 months Interval 1.2 to 1.5	2.8 months Interval 1.4 to 6.9

Adverse Events

Trametinib

Serious events: 13 serious events

Other events: 21 other events

Deaths: 0 deaths

Chemotherapy

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

SWOG Statistician

SWOG Statistics & Data Management Center

Phone: 206-667-4408

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Trametinib n=23 participants at risk Patients receive trametinib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Chemotherapy n=20 participants at risk Patients receive either A) leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46-48 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity or B) capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Cardiac disorders Cardiac arrest	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Gastrointestinal disorders Esophageal varices hemorrhage	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Gastrointestinal disorders Gastric hemorrhage	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Gastrointestinal disorders Gastric ulcer	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Gastrointestinal disorders Gastritis	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Gastrointestinal disorders Gastrointestinal disorders-Other	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Gastrointestinal disorders Obstruction gastric	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
General disorders Fever	8.7% 2/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Hepatobiliary disorders Hepatobiliary disorders-Other	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Infections and infestations Infections and infestations-Other	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Infections and infestations Sepsis	13.0% 3/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Investigations Alanine aminotransferase increased	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Investigations Aspartate aminotransferase increased	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Investigations Blood bilirubin increased	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified - Other	8.7% 2/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	5.0% 1/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Nervous system disorders Intracranial hemorrhage	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Nervous system disorders Presyncope	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Psychiatric disorders Confusion	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Respiratory, thoracic and mediastinal disorders Epistaxis	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory failure	4.3% 1/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.
Vascular disorders Thromboembolic event	8.7% 2/23 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.	0.00% 0/20 • Up to 2 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.