A Single-Arm, Phase II Study of Autophagy Modulation Using Hydroxychloroquine in Combination With Encorafenib and Cetuximab or Panitumumab in Metastatic BRAF-mutated Colorectal Cancer Refractory to Standard Therapies
Northwestern University
Summary
This is a Phase II, open label, single-arm trial study of adding hydroxychloroquine to encorafenib and cetuximab in patients with metastatic BRAF V600E colon cancer with progression on at least 1 prior line of therapy. We hypothesize that autophagy is a major mechanism of resistance to BRAF inhibition in stage IV BRAF V600E colorectal cancer, and that the addition of hydroxychloroquine to standard encorafenib and cetuximab therapy will help overcome this resistance.
Description
Primary Objective -Determine the Objective Response Rate (ORR) of encorafenib, cetuximab or panitumumab, and hydroxychloroquine in patients with stage IV BRAF V600E mutated colorectal cancer. Secondary Objectives -Determine progression-free survival (PFS) of patients treated with encorafenib, cetuximab or panitumumab, and hydroxychloroquine. Note: progression is defined as either radiological progression (with CT scan) OR clinical progression, which will be defined as 'clinical deterioration associated with rising CEA biomarker' (laboratory date of collection of sample to be noted). * Dete…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Patients must have histologically confirmed stage IV colorectal cancer positive for BRAF V600E mutation and on at least 1 prior line of systemic therapy and have not had any previous BRAF inhibitor therapy Patients must have measurable disease as defined by RECIST 1.1 See Section 7 for the evaluation of measurable disease. Baseline imaging scan will be used. * Patients must have discontinued prior chemotherapy or targeted therapy at least 14 days prior to D1 of starting study treatment (E+C). Note: patients are allowed to start standard of care treatment with Encorafenib…
Interventions
- DrugHydroxychloroquine in Combination With Encorafenib and Cetuximab or Panitumumab
Prior to starting therapy, patients will have a pretreatment cross-sectional scan. Patients will then begin with encorafenib 300 mg daily starting with Cycle 1 day 1; then patients will receive IV cetuximab weekly, with 400 mg/m2 on C1D1 as a loading dose and 250 mg/m2 on all other days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Location
- Northwestern UniversityChicago, Illinois