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Clinical Trials/EUCTR2018-000271-32-AT
EUCTR2018-000271-32-ATActive, not recruitingPhase 1

Phase II, open-label, single arm, multicenter study of encorafenib, binimetinib plus cetuximab in subjects with previously untreated BRAF V600E -mutant Metastatic Colorectal Cancer - ANCHOR CRC Study

Pierre Fabre Médicament0 sites95 target enrollmentStarted: November 28, 2018Last updated:
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Drugs

Trial Snapshot

Phase
Phase 1
Status
Active, not recruiting
Sponsor
Enrollment
95
Study OverviewEligibility CriteriaInvestigatorsRecords & IdentifiersSimilar Trials

Study Overview

Brief Summary

No summary available.

Study Design

Study Type
Interventional clinical trial of medicinal product

Eligibility Criteria

Sex
All

Inclusion Criteria

  • •1. Provide a signed and dated informed consent form.
  • •2. Male or female = 18 years of age at time of informed consent.
  • •3. Histologically or cytologically confirmed CRC that is metastatic and unresectable at time of study entry (i.e. not suitable for complete surgical resection at screening).
  • •4. Presence of BRAFV600E mutation in tumor tissue previously determined by a local assay at any time prior to screening.
  • •Notes: a. Only PCR and NGS-based local assays results will be acceptable.
  • •b. If at any time there is lack of confirmation of the BRAFV600E mutation in a total of 6 subjects 6% of the total targeted 90 treated subjects) or discordance between the local assay and the central laboratory in 3 subjects (= 3% of the total targeted 90 treated subjects), all subsequent subjects will be required to have BRAFV600E determined by the central lab. prior to study treatment assignment.
  • •c. Central testing cannot be repeated to resolve discordances with a local result once the central lab. delivers a definitive result (positive or negative).
  • •d. If the result from the central lab. is indeterminate or the sample is deemed inadequate for testing, additional samples may be submitted (archival material only).
  • •e. If more than 1 discordant result from any local lab. lead to subject enrollment, subsequent results from this local lab. will not be accepted for further subject enrollment.
  • •5. Eligible to receive cetuximab per locally approved label with regards to tumor RAS status
  • •e.g.: In agreement with EU label, evidence of wild type RAS (KRAS and NRAS) status in EU countries
  • •6. Able to provide a sufficient amount of representative tumor specimen (primary or metastatic, archival or newly obtained) for testing of BRAF and RAS mutation status. Note: (FFPE tumor tissue block or a minimum of 10 slides, optimally up to 15 slides)
  • •7. Evidence of measurable disease, as per RECIST 1.1.
  • •Note: Lesions in areas of prior radiotherapy or other loco-regional therapies are considered measurable only if progression has been documented in the region following therapy.
  • •8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • •9. Adequate bone marrow function at screening and baseline:
  • •i. Absolute neutrophil count (ANC) = 1.5 x 1 000 000 000 /L.
  • •ii. Platelets = 100 x 1 000 000 000/L
  • •iii. Hemoglobin = 9.0 g/dL.
  • •Blood transfusions are allowed provided that the subject has not received more than 2 units of red blood cells in the 4 weeks prior to achieve the minimum required hemoglobin level.
  • •10. Adequate renal function at screening and baseline:
  • •i. Serum creatinine = 1.5x upper limit of normal (ULN).
  • •ii. Calculated creatinine clearance (CrCl)= 50 mL/min by Cockroft-Gault formula.
  • •11. Adequate electrolytes at screening and baseline, defined as serum potassium and magnesium levels within institutional normal limits.
  • •Replacement treatment to achieve adequate electrolytes will be allowed
  • •12. Adequate hepatic function at screening and baseline:
  • •i. Serum total bilirubin = 1.5 x ULN and < 2 mg/dL.Total bilirubin > 1.5 x ULN is allowed if direct (conjugated) bilirubin is = 1.5 x ULN (and indirect (unconjugated) bilirubin is = 4.25 x ULN – Only applicable for France).
  • •ii. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) = 2.5 x ULN, or = 5 x ULN in the presence of liver metastases.
  • •13. Adequate cardiac function at screening:
  • •i. Left ventricular ejection fraction (LVEF) = 50% as determined by MUGA scan or ECHO.
  • •ii. Mean triplicate QT interval correcte

Exclusion Criteria

  • •1. Prior systemic therapy for metastatic disease.
  • •Note: previous adjuvant/neoadjuvant therapy is allowed provided that 1) the interval from the end of chemotherapy to relapse is >6 months OR 2) in the case of neoadjuvant therapy, complete surgical resection was achieved and the interval from the end of chemotherapy to relapse is >12 months. Prior locoregional radiotherapy is allowed.
  • •2. Prior treatment with any RAF inhibitor, MEK inhibitor, cetuximab or other anti- EGFR treatment.
  • •3. Symptomatic brain metastasis.
  • •Note: subjects previously treated or untreated for these conditions who are asymptomatic in the absence of corticosteroid and anti-epileptic therapy are allowed. Brain metastases must be stable for = 4 weeks with imaging
  • •4. Leptomeningeal disease.
  • •5. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity syndrome or hypercoagulability syndrome.
  • •6. Use of any herbal medications/supplements or any medications or foods that are moderate or strong inhibitors or inducers of CYP3A4/5 = 1 week prior to the start of treatment.
  • •Note: However, subjects who either discontinue moderate or strong inhibitors or inducers of CYP3A4/5 or switch to another medication at least 7 days prior to starting study treatment are eligible.
  • •7. Known history of acute or chronic pancreatitis within 6 months prior to the start of the treatment.
  • •8. History of chronic inflammatory bowel disease or Crohn’s disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) = 12 months prior to first dose.
  • •9. Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:
  • •i. History of acute myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft, coronary angioplasty or stenting) = 6 months prior to start of study treatment.
  • •ii. Symptomatic congestive heart failure (Grade 2 or higher), history or current evidence of clinically significant arrhythmia and/or conduction abnormality = 6 months prior to start of study treatment, except atrial fibrillation and paroxysmal supraventricular tachycardia.
  • •10. Uncontrolled hypertension defined as persistent elevation of systolic blood pressure = 150 mmHg or diastolic blood pressure = 100 mmHg despite optimal therapy.
  • •11. Impaired hepatic function, defined as Child-Pugh class B or C.
  • •12. No more applicable from protocol V6
  • •13. Impaired gastrointestinal function or disease which may significantly alter the absorption of encorafenib or binimetinib or recent changes in bowel function suggesting current or impending bowel obstruction.
  • •14. Previous or concurrent malignancy within 5 years of study entry or other noninvasive or indolent malignancy without Sponsor approval except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix.
  • •15. History of thromboembolic or cerebrovascular events = 6 months prior to starting study treatment including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli.
  • •16. Concurrent neuromuscular disorder that is associated with the potential of elevated Creatine Kinase e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy.
  • •17. Residual CTCAE = Grade 2 toxicity from any prior anticanc

Investigators

Sponsor
Pierre Fabre Médicament

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