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NCT04566133

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

Terminated Phase 2 Results posted Last updated 21 August 2023
What this trial tests

Phase 2 trial testing Trametinib in Bile Duct Cancer in 2 participants. Terminated before completion.

Timeline
15 February 2022
Primary endpoint
11 May 2022
31 December 2022

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment2
Start date15 February 2022
Primary completion11 May 2022
Estimated completion31 December 2022
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Bile Duct Cancer or Biliary Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Median Progression Free Survival (PFS) Primary · 3 months

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

GroupValue95% CI
Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ)2.48NA – NA
Proportion of Participants With a Response (Complete Response (CR) + Partial Response (PR) Reported With an 80% Confidence Interval Secondary · 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

Complete Response
GroupValue95% CI
Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ)00 – 0
Partial Response
GroupValue95% CI
Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ)00 – 0
Proportion of Participants With a Response (Complete Response (CR) + Partial Response (PR) Reported With an 95% Confidence Interval Secondary · 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

Complete Response
GroupValue95% CI
Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ)00 – 0
Partial Response
GroupValue95% CI
Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ)00 – 0
Serious Adverse Events Possibly, Probably, and/or Definitely Related to Treatment Secondary · 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.

GroupValue95% CI
Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ)0
Overall Survival Secondary · 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.

GroupValue95% CI
Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ)3.1NA – NA
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) Secondary · 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

GroupValue95% CI
Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ)2

Adverse events — posted to ClinicalTrials.gov

Time frame: 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.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1/Arm 1: Trametinib + Hydroxychloroquine (HCQ)
Serious: 0/2 (0%)
Deaths: 2/2
Other adverse events (24 terms — click to expand)

ReactionSystemCohort 1/Arm 1: Trametinib…
FlatulenceGastrointestinal disorders
Rash acneiformSkin and subcutaneous tissue disorders
BelchingGastrointestinal disorders
DiarrheaGastrointestinal disorders
Stomach painGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Alkaline phosphatase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Creatinine increasedInvestigations
EosinophiliaInvestigations
Lymphocyte count decreasedInvestigations
Platelet count decreasedInvestigations
HyperglycemiaMetabolism and nutrition disorders
HyperphosphatemiaMetabolism and nutrition disorders
HypoalbuminemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
PainGeneral disorders
Sore throatRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, Two small pustule mouth lesionsSkin and subcutaneous tissue disorders

Data from ClinicalTrials.gov NCT04566133 adverse events section.

Sponsor's own description

Background: Bile duct cancer is cancer of the slender tubes of the biliary tract. These tubes carry bile through the liver. Such cancer tumors often have an abnormal or mutated gene. Researchers think a mix of drugs can slow the progression of gene-mutated cancers of the biliary tract. Objective: To see if using a combination of trametinib and hydroxychloroquine (HCQ) increases the period of time it takes for a person s bile tract carcinoma (BTC) to get worse. Eligibility: Adults age 18 and older with BTC. Design: Participants will be screened with a physical exam, medical history, and cancer history. Their ability to do their normal activities will be assessed. They will have blood and urine tests. They will give a tumor sample. They will have heart tests. They may talk with a heart doctor. They may have an eye exam. They may have a tuberculosis test. They will have computer tomography (CT) scans of the chest, abdomen, and pelvis. They may have magnetic resonance imaging (MRI) scans of the chest, abdomen, pelvis. Participants will repeat some screening tests throughout the study. Participants will take HCQ and trametinib tablets by mouth daily in 28-day cycles. They will have study visits once a month. They will take the drugs until they have bad side effects or the drugs stop working. Participants will have one more tumor biopsy during the treatment. They will have blood taken often. One month after treatment ends, participants will have a safety follow-up visit. Then they will be called or emailed every 6 months for the rest of their life....

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Role of lysosomes in physiological activities, diseases, and therapy.
    Zhang Z, Yue P, Lu T, Wang Y, et al · · 2021 · cited 238× · PMID 33990205 · DOI 10.1186/s13045-021-01087-1
  2. Metabolic reprogramming and its clinical implication for liver cancer.
    Yang F, Hilakivi-Clarke L, Shaha A, Shaha A, et al · · 2023 · cited 112× · PMID 36626639 · DOI 10.1097/hep.0000000000000005
  3. Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.
    Yin G, Huang J, Petela J, Jiang H, et al · · 2023 · cited 50× · PMID 37221195 · DOI 10.1038/s41392-023-01441-4
  4. KRAS Mutations in Solid Tumors: Characteristics, Current Therapeutic Strategy, and Potential Treatment Exploration.
    Yang Y, Zhang H, Huang S, Chu Q. · · 2023 · cited 50× · PMID 36675641 · DOI 10.3390/jcm12020709
  5. Concurrent Inhibition of IGF1R and ERK Increases Pancreatic Cancer Sensitivity to Autophagy Inhibitors.
    Stalnecker CA, Grover KR, Edwards AC, Coleman MF, et al · · 2022 · cited 47× · PMID 34921013 · DOI 10.1158/0008-5472.can-21-1443
  6. Autophagy Regulation on Cancer Stem Cell Maintenance, Metastasis, and Therapy Resistance.
    Wang X, Lee J, Xie C. · · 2022 · cited 38× · PMID 35053542 · DOI 10.3390/cancers14020381
  7. Onco-immunomodulatory properties of pharmacological interference with RAS-RAF-MEK-ERK pathway hyperactivation.
    Avery TY, Köhler N, Zeiser R, Brummer T, et al · · 2022 · cited 31× · PMID 35965494 · DOI 10.3389/fonc.2022.931774
  8. The Crosstalk between Autophagy and Nrf2 Signaling in Cancer: from Biology to Clinical Applications.
    Shan C, Wang Y, Wang Y. · · 2024 · cited 27× · PMID 39664581 · DOI 10.7150/ijbs.103187

Verify or expand the search:

Other trials of Trametinib

Trials testing the same drug.

Other recruiting trials for Bile Duct Cancer

Currently open trials in the same condition.

Other National Cancer Institute (NCI) trials

Trials by the same sponsor.

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Data sources for this page

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