Trial Outcomes & Findings for Combination of Trametinib (MEK Inhibitor) and Hydroxychloroquine (HCQ) (Autophagy Inhibitor) in Patients With KRAS Mutation Refractory Bile Tract Carcinoma (BTC). (NCT NCT04566133)

Last Updated: 2023-08-21

Results Overview

Participants with refractory bile tract carcinoma (BTC) with KRAS mutation that exceed 25% who receive trametinib plus hydroxychloroquine (HCQ) combination who are able to not have progressive disease at 5 months will be reported along with a 95% confidence interval. Progression was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progression).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

2 participants

Primary outcome timeframe

3 months

Results posted on

2023-08-21

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ) Participants with bile tract carcinoma (BTC) or carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of BTC. Participants receive 2 mg of Trametinib orally once a day of every cycle, and 600 mg of hydroxychloroquine orally twice a day every cycle (1200 mg total dose).
Overall Study STARTED	2
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Combination of Trametinib (MEK Inhibitor) and Hydroxychloroquine (HCQ) (Autophagy Inhibitor) in Patients With KRAS Mutation Refractory Bile Tract Carcinoma (BTC).

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ) n=2 Participants Participants with bile tract carcinoma (BTC) or carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of BTC. Participants receive 2 mg of Trametinib orally once a day of every cycle, and 600 mg of hydroxychloroquine orally twice a day every cycle (1200 mg total dose).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	41.95 years STANDARD_DEVIATION 16.76 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants

PRIMARY outcome

Timeframe: 3 months

Outcome measures

Outcome measures
Measure	Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ) n=2 Participants Participants with bile tract carcinoma (BTC) or carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of BTC. Participants receive 2 mg of Trametinib orally once a day of every cycle, and 600 mg of hydroxychloroquine orally twice a day every cycle (1200 mg total dose).
Median Progression Free Survival (PFS)	2.48 Months It is mathematically not possible to provide a confidence interval for 2 participants.

SECONDARY outcome

Timeframe: Every 2 months up to approximately 10 months

Response is defined as a Complete Response (CR) + Partial Response (PR) in participants with refractory BTC with KRAS mutation treated with the combination of trametinib plus HCQ. Response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response (CR) is disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. Any pathological lymph nodes must have reduction in short axis to \<10 mm. Partial Response (PR) is at least a 30% decrease in the sum of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ) n=2 Participants Participants with bile tract carcinoma (BTC) or carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of BTC. Participants receive 2 mg of Trametinib orally once a day of every cycle, and 600 mg of hydroxychloroquine orally twice a day every cycle (1200 mg total dose).
Proportion of Participants With a Response (Complete Response (CR) + Partial Response (PR) Reported With an 80% Confidence Interval Complete Response	0 Proportion of participants Interval 0.0 to 0.0
Proportion of Participants With a Response (Complete Response (CR) + Partial Response (PR) Reported With an 80% Confidence Interval Partial Response	0 Proportion of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Every 2 months up to approximately 10 months

Outcome measures

Outcome measures
Measure	Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ) n=2 Participants Participants with bile tract carcinoma (BTC) or carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of BTC. Participants receive 2 mg of Trametinib orally once a day of every cycle, and 600 mg of hydroxychloroquine orally twice a day every cycle (1200 mg total dose).
Proportion of Participants With a Response (Complete Response (CR) + Partial Response (PR) Reported With an 95% Confidence Interval Complete Response	0 proportion of participants Interval 0.0 to 0.0
Proportion of Participants With a Response (Complete Response (CR) + Partial Response (PR) Reported With an 95% Confidence Interval Partial Response	0 proportion of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 90 days after treatment

Adverse events were assessed by the by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ) n=2 Participants Participants with bile tract carcinoma (BTC) or carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of BTC. Participants receive 2 mg of Trametinib orally once a day of every cycle, and 600 mg of hydroxychloroquine orally twice a day every cycle (1200 mg total dose).
Serious Adverse Events Possibly, Probably, and/or Definitely Related to Treatment	0 adverse events

SECONDARY outcome

Timeframe: duration of time from the start of treatment to death from any cause, approximately 10 months

Overall survival is defined as the duration of time from start of treatment to death from any cause.

Outcome measures

Outcome measures
Measure	Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ) n=2 Participants Participants with bile tract carcinoma (BTC) or carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of BTC. Participants receive 2 mg of Trametinib orally once a day of every cycle, and 600 mg of hydroxychloroquine orally twice a day every cycle (1200 mg total dose).
Overall Survival	3.1 Months It is mathematically not possible to provide a confidence interval for 2 participants.

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, assessed for approximately 3 months and 25 days

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ) n=2 Participants Participants with bile tract carcinoma (BTC) or carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of BTC. Participants receive 2 mg of Trametinib orally once a day of every cycle, and 600 mg of hydroxychloroquine orally twice a day every cycle (1200 mg total dose).
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	2 Participants

Adverse Events

Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 2 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ) n=2 participants at risk Participants with bile tract carcinoma (BTC) or carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of BTC. Participants receive 2 mg of Trametinib orally once a day of every cycle, and 600 mg of hydroxychloroquine orally twice a day every cycle (1200 mg total dose).
Gastrointestinal disorders Belching	50.0% 1/2 • Number of events 1 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Gastrointestinal disorders Diarrhea	50.0% 1/2 • Number of events 1 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Gastrointestinal disorders Flatulence	100.0% 2/2 • Number of events 2 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Gastrointestinal disorders Stomach pain	50.0% 1/2 • Number of events 1 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Investigations Alanine aminotransferase increased	50.0% 1/2 • Number of events 4 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Investigations Alkaline phosphatase increased	50.0% 1/2 • Number of events 1 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Investigations Aspartate aminotransferase increased	50.0% 1/2 • Number of events 2 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Investigations Creatinine increased	50.0% 1/2 • Number of events 1 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Investigations Eosinophilia	50.0% 1/2 • Number of events 2 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Investigations Lymphocyte count decreased	50.0% 1/2 • Number of events 2 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Investigations Platelet count decreased	50.0% 1/2 • Number of events 1 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Metabolism and nutrition disorders Hyperglycemia	50.0% 1/2 • Number of events 2 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Metabolism and nutrition disorders Hyperphosphatemia	50.0% 1/2 • Number of events 1 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Metabolism and nutrition disorders Hypoalbuminemia	50.0% 1/2 • Number of events 2 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Metabolism and nutrition disorders Hypokalemia	50.0% 1/2 • Number of events 1 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Metabolism and nutrition disorders Hypomagnesemia	50.0% 1/2 • Number of events 1 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Metabolism and nutrition disorders Hyponatremia	50.0% 1/2 • Number of events 2 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Musculoskeletal and connective tissue disorders Arthralgia	50.0% 1/2 • Number of events 1 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
General disorders Pain	50.0% 1/2 • Number of events 1 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Respiratory, thoracic and mediastinal disorders Sore throat	50.0% 1/2 • Number of events 1 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Skin and subcutaneous tissue disorders Pruritus	50.0% 1/2 • Number of events 1 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Skin and subcutaneous tissue disorders Rash acneiform	100.0% 2/2 • Number of events 2 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Skin and subcutaneous tissue disorders Rash maculo-papular	50.0% 1/2 • Number of events 2 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, Two small pustule mouth lesions	50.0% 1/2 • Number of events 1 • Adverse events assessed from the date treatment consent signed to date off study, approximately 3 months and 25 days. Adverse Events monitored/assessed for approximately 3 months and 25 days; All-Cause Mortality monitored/assessed up to 10 months. The participants died due to their underlying disease.

Additional Information

Dr. Tim F. Greten

National Cancer Institute

Phone: 2407606114

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place