Trial record 1 of 1 for:
05564403
Study of Chemotherapy, With or Without Binimetinib in Advanced Biliary Tract Cancers in 2nd Line Setting (A ComboMATCH Treatment Trial)
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| ClinicalTrials.gov Identifier: NCT05564403 |
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Recruitment Status :
Recruiting
First Posted : October 3, 2022
Last Update Posted : May 1, 2024
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Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
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Brief Summary:
This phase II ComboMATCH treatment trial compares the usual treatment of modified leucovorin, fluorouracil and oxaliplatin (mFOLFOX6) chemotherapy to using binimetinib plus mFOLFOX6 chemotherapy to shrink tumors in patients with biliary tract cancers that have spread to other places in the body (advanced) and had progression of cancer after previous treatments (2nd line setting). Fluorouracil is in a class of medications called antimetabolites. It works by slowing or stopping the growth of cancer cells in the body. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It works by killing tumor cells. Leucovorin may help the other drugs in the mFOLFOX6 chemotherapy regimen work better by making tumor cells more sensitive to the drugs. Binimetinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals tumor cells to multiply. This helps to stop or slow the spread of tumor cells. Giving binimetinib in combination with mFOLFOX6 chemotherapy may be effective in shrinking or stabilizing advanced biliary tract cancers in the 2nd line setting.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Recurrent Biliary Tract Carcinoma Recurrent Distal Bile Duct Adenocarcinoma Recurrent Gallbladder Carcinoma Recurrent Intrahepatic Cholangiocarcinoma Stage III Distal Bile Duct Cancer AJCC v8 Stage III Hilar Cholangiocarcinoma AJCC v8 Stage III Intrahepatic Cholangiocarcinoma AJCC v8 Stage IV Distal Bile Duct Cancer AJCC v8 Stage IV Hilar Cholangiocarcinoma AJCC v8 Stage IV Intrahepatic Cholangiocarcinoma AJCC v8 Unresectable Biliary Tract Carcinoma Unresectable Distal Bile Duct Adenocarcinoma Unresectable Gallbladder Carcinoma Unresectable Intrahepatic Cholangiocarcinoma | Drug: Binimetinib Procedure: Biopsy Procedure: Biospecimen Collection Procedure: Bone Scan Procedure: Computed Tomography Procedure: Echocardiography Drug: Fluorouracil Drug: Leucovorin Calcium Procedure: Magnetic Resonance Imaging Procedure: Multigated Acquisition Scan Drug: Oxaliplatin | Phase 2 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 66 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | FOLFOX in Combination With Binimetinib as 2nd Line Therapy for Patients With Advanced Biliary Tract Cancers With MAPK Pathway Alterations: A ComboMATCH Treatment Trial |
| Actual Study Start Date : | February 9, 2024 |
| Estimated Primary Completion Date : | January 21, 2025 |
| Estimated Study Completion Date : | January 21, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Cholangiocarcinoma
Drug Information
available for:
Binimetinib
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Arm 1 (mFOLFOX6)
Patients receive leucovorin IV over 30 minutes on day 1, oxaliplatin IV over 30 minutes on day 1, and fluorouracil IV over 46-48 hours on days 1-2. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or a FDG-PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated.
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Procedure: Biopsy
Undergo biopsy
Other Names:
Procedure: Biospecimen Collection Undergo collection of blood
Other Names:
Procedure: Bone Scan Undergo bone scan
Other Name: Bone Scintigraphy Procedure: Computed Tomography Undergo CT
Other Names:
Procedure: Echocardiography Undergo ECHO
Other Name: EC Drug: Fluorouracil Given IV
Other Names:
Drug: Leucovorin Calcium Given IV
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
Procedure: Multigated Acquisition Scan Undergo MUGA
Other Names:
Drug: Oxaliplatin Given IV
Other Names:
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Experimental: Arm 2 (binimetinib, mFOLFOX6)
Patients receive binimetinib orally (PO) on days 1-14, and leucovorin IV, oxaliplatin IV, and fluorouracil IV as in Arm 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or an FDG-PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated.
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Drug: Binimetinib
Given PO
Other Names:
Procedure: Biopsy Undergo biopsy
Other Names:
Procedure: Biospecimen Collection Undergo collection of blood
Other Names:
Procedure: Bone Scan Undergo bone scan
Other Name: Bone Scintigraphy Procedure: Computed Tomography Undergo CT
Other Names:
Procedure: Echocardiography Undergo ECHO
Other Name: EC Drug: Fluorouracil Given IV
Other Names:
Drug: Leucovorin Calcium Given IV
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
Procedure: Multigated Acquisition Scan Undergo MUGA
Other Names:
Drug: Oxaliplatin Given IV
Other Names:
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Primary Outcome Measures :
- Overall survival (OS) [ Time Frame: From randomization to the time of death due to any cause, assessed up to 30 months ]The primary efficacy analysis will be to compare the OS distributions between those treated with modified leucovorin, fluorouracil and oxaliplatin (mFOLFOX6) and binimetinib versus (vs.) mFOLFOX6. Despite being a randomized phase II trial, we will utilize an intent to treat approach such that patients will be analyzed based on the treatment arm to which they were randomized. As defined above, OS will be compared between the two treatment arms using Kaplan-Meier methods. The hazard ratio, median OS, and estimated OS rates at 6, 12, 18, 24, and 30 months will be estimated along with corresponding 95% confidence intervals. Anticipating that the treatment arms will be balanced in terms of the potential confounders reflect in the stratification factors, a log-rank test will be used to compare the OS distributions between the two treatment arms in this cohort.
Secondary Outcome Measures :
- Objective response [ Time Frame: Up to 5 years ]Objective response by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria will be estimated using objective response rate (ORR) where ORR is defined as the number of evaluable patients achieving a response (partial response [PR] or complete response [CR] per RECIST v1.1) during treatment with study therapy divided by the total number of evaluable patients. Rates of response will be compared across arms using a Chi-Square Test for Proportion. Point estimates will be generated for objective response rates within each arm along with 95% confidence intervals using the Clopper-Pearson method.
- Progression free survival (PFS) [ Time Frame: From study entry to the first of either disease progression or death from any cause, assessed up to 5 years ]Disease progression will be determined based on RECIST 1.1 criteria. PFS will be estimated using the Kaplan-Meier method. The median PFS and 95% confidence interval will be reported. Patients will be censored at the last disease assessment date.
- Duration of response (DoR) [ Time Frame: Up to 5 years ]Defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented, or death if no prior evidence of disease progression. The distribution of DoR will be estimated using the method of Kaplan-Meier.
- Clinical benefit [ Time Frame: Up to 5 years ]Defined as achieving CR, PR, or stable disease (SD) for at least 4 months while on treatment. Disease status will be assessed using RECIST v. 1.1 criteria. Clinical benefit rate (CBR) will be calculated as the proportion of evaluable patients who achieve clinical benefit. The final CBR point estimate and corresponding 95% confidence interval calculated using Clopper-Pearson method.
- Incidence of adverse events [ Time Frame: Up to 5 years ]Patients will be evaluated for adverse events using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events version 5.0. Summary statistics (e.g., mean, median, standard deviation) and frequency tables will be used to describe the distributions of adverse events. Rates of adverse events occurring in the treatment arm will be compared to the control arm with chi-squared tests (or suitable alternative) used for comparisons where applicable. Tolerability will also be evaluated, summarizing rates of dose delays or modifications, reasons patients end treatment, and time to end of active treatment.
Other Outcome Measures:
- Prognostic model/scoring system [ Time Frame: Up to 5 years ]Defined as presence of peritoneal disease/locally advanced disease/metastatic disease, Eastern Cooperative Oncology Group (ECOG) performance status, CA19.9 level. Will fit multivariate Cox regression models including MAPK mutation status, presence of peritoneal disease/locally advance disease/metastatic disease, ECOG performance status, and CA19-9 level, stratified by treatment arm. We will calculate C-statistics with 5-fold cross-validation
- Albumin [ Time Frame: Up to 5 years ]Will correlate outcome with albumin.
- Presence of MAPK pathway mutations [ Time Frame: Up to 5 years ]Will correlate with activity of addition of binimetinib therapy to standard 2nd line chemotherapy.
- Activity of addition of binimetinib therapy to standard 2nd line chemotherapy [ Time Frame: Up to 5 years ]Will correlate with presence of MAPK pathway mutations.
- Whole-exome sequencing and ribonucleic acid (RNA)-sequencing [ Time Frame: Up to 5 years ]Will be used to assess determinants of response and resistance. Concordance of diagnostic tumor mutation profile generated by the Designated Laboratory, the pre-treatment biopsy mutation profile, and the pre-treatment circulating tumor deoxyribonucleic acid (ctDNA) mutation profile will be assessed. Details are provided in the statistical plan of the ComboMATCH Registration Protocol.
- Changes in plasma MAPK mutations allelic burden and other molecular findings [ Time Frame: Up to 5 years ]Will correlate changes with clinical activity, disease course as well as response/resistance to therapy.
- Detection of mutations as well as prediction of outcomes [ Time Frame: Up to 5 years ]Will evaluate if our machine learning algorithm for RAS/RAF/MEK/ERK pathway mutations correlates with detection of mutations as well as prediction of outcomes from samples obtained in this study.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-A6 based on the presence of an actionable mutation as defined in EAY191
- Patients must be registered to the ComboMATCH Registration Protocol (EAY191)
- Patients must have RAS/RAF/MEK/ERK mutations as determined by the ComboMATCH screening assessment
- Patients must have disease that can be safely biopsied and agree to a pre-treatment biopsy or have archival tissue available from within 12 months prior to registration
- Please note the current actionable marker of interest (aMOI)/actionable alteration list for this treatment trial can be found on the Cancer Trials Support Unit (CTSU) website: www.ctsu.org (final uniform resource locator [URL] pending).
- Please note novel/Dynamic aMOI can be submitted for review per the process described in the ComboMATCH Registration Protocol
- Participants must have histologically confirmed BTC (intrahepatic cholangiocarcinoma [IHC], extrahepatic cholangiocarcinoma [EHC] or gallbladder cancer [GBC]) that is unresectable or recurrent with a confirmed RAS/RAF/MEK/ERK pathway mutation via any Clinical Laboratory Improvement Act (CLIA)-certified method. BRAFV600E mutations are not eligible due to other ongoing/upcoming studies in this disease cohort
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Of note, in the case when a baseline biopsy is done after scans are obtained, a lesion separate from one that is biopsied needs to be measurable per RECIST 1.1. All radiologic studies must be performed within 28 days prior to randomization
- Progression of disease on gemcitabine based first-line regimen
- No systemic anti-cancer therapy within 4 weeks of registration to EAY191-A6
- No prior MEK inhibitor therapy
- No prior history of treatment with a direct and specific inhibitor of KRAS
- Patients who only received radio-sensitizing chemotherapy with fluorouracil (5-FU) or capecitabine, are eligible but need to have received and failed first-line systemic chemotherapy upon recurrence. Peri-operative systemic 5-FU/capecitabine and/or oxaliplatin, is allowed if it's been more than 12 months of registration to EAY191-A6
- No major surgery within 4 weeks (excluding placement of vascular access) of registration to EAY191-A6
- No minor surgery within 2 weeks of registration to EAY191-A6
- No palliative radiotherapy within 1 week of registration to EAY191-A6
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Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
- Therefore, for women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
- Adequate contraception is needed for at least 30 days after the last dose of binimetinib and breastfeeding should be discontinued for at least 3 days after the last dose of binimetinib. For FOLFOX regimen, 9 months is recommended for contraception after last dose of oxaliplatin for females of childbearing potential and 6 months for males
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Absolute neutrophil count (ANC) >= 1,000/mm^3, no growth factor within 14 days of 1st dose
- Platelet count >= 75,000/mm^3
- Creatinine < 1.6 x upper limit of normal (ULN)
- Calculated (Calc.) creatinine clearance >= 50 mL/min, as calculated by the Cockcroft-Gault formula
- Total bilirubin =< 2.0 x upper limit of normal (ULN) patients with Gilbert syndrome may enroll if total bilirubin < 3.0 mg/dL (51 umole/L)
- Aspartate aminotransferase (AST) /alanine aminotransferase (ALT) =< 5.0 x upper limit of normal (ULN)
- Hemoglobin >= 8 g/dL, no transfusion within 14 days of 1st dose
- Albumin >= 3 g/dL (451 micromole/L)
- Creatine phosphokinase =< 2.5 x ULN
- No history of interstitial lung disease. No history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
- Must have adequate cardiac function with left ventricular ejection fraction >= 50% by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan. Patients with congenital long QT syndrome are not permitted. Baseline corrected QT (QTc) interval < 460ms for women and =< 450ms for men (average of triplicate readings) (CTCAE Grade 1) using Fridericia's QT correction formula. NOTE: This criterion does not apply to patients with a right or left bundle branch block. Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA]), myocardial infarction within the last 6 months, unstable arrhythmias, unstable angina or severe obstructive pulmonary disease
- No active skin disorder that has required systemic therapy within the past 1 year
- No history of rhabdomyolysis
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No concurrent ocular disorders, including:
- Patients with history of glaucoma, history of retinal vein occlusion (RVO), predisposing factors for RVO, including but not limited to uncontrolled hypertension, uncontrolled diabetes
- Patients with history of retinal pathology or evidence of visible retinal pathology that is considered a risk factor for RVO, intraocular pressure > 21 mm Hg as measured by tonometry, or other significant ocular pathology, such as anatomical abnormalities that increase the risk for RVO
- Patients with a history of corneal erosion (instability of corneal epithelium), corneal degeneration, active or recurrent keratitis, and other forms of serious ocular surface inflammatory conditions
- Patients with known or at risk for retinopathies, uveitis or retinal vein occlusion
- No patients with a history of hypersensitivity to any of the inactive ingredients in binimetinib, nor known severe allergic reactions or hypersensitivity of 5-FU, leucovorin (LV) or oxaliplatin will be allowed to participate in this study for safety concerns
- No other medical condition (e.g. cardiac, gastrointestinal, pulmonary, psychiatric, neurological, genetic, etc.) that in the opinion of the investigator would places the subject at unacceptably high risk for toxicity
- No prior allogeneic stem cell or solid organ transplantation
- Central nervous system (CNS) metastases must have been treated with local therapy (surgery, radiation, ablation) with systemic steroids tapered to a physiologic dose (10 mg or prednisone equivalent or less)
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Exclusion Criteria:
- Patients must not have BRAF V600E as determined by the ComboMATCH screening assessment
- High blood pressure more than 160/90 despite treatment are ineligible
- Patients should not have history of bowel perforation or intestinal fistulas in the last 6 months
- Patients with the inability to swallow oral medications or impaired gastrointestinal absorption due to gastrectomy or active inflammatory bowel disease are ineligible
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05564403
Locations
Show 148 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Ardaman Shergill | Alliance for Clinical Trials in Oncology |
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT05564403 |
| Other Study ID Numbers: |
NCI-2022-07833 NCI-2022-07833 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) EAY191-A6 ( Other Identifier: Alliance for Clinical Trials in Oncology ) EAY191-A6 ( Other Identifier: CTEP ) U10CA180821 ( U.S. NIH Grant/Contract ) |
| First Posted: | October 3, 2022 Key Record Dates |
| Last Update Posted: | May 1, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page. |
| URL: | https://grants.nih.gov/policy/sharing.htm |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
Additional relevant MeSH terms:
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Carcinoma Adenocarcinoma Cholangiocarcinoma Biliary Tract Neoplasms Bile Duct Neoplasms Klatskin Tumor Gallbladder Neoplasms Carcinoma, Ductal Recurrence Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Disease Attributes Pathologic Processes Digestive System Neoplasms |
Neoplasms by Site Biliary Tract Diseases Digestive System Diseases Bile Duct Diseases Gallbladder Diseases Neoplasms, Ductal, Lobular, and Medullary Calcium, Dietary Leucovorin Folic Acid Fluorouracil Oxaliplatin Calcium Levoleucovorin Calcium-Regulating Hormones and Agents Physiological Effects of Drugs |