Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Anti-Infective Agents

Antirheumatic Agents

All Drugs and Chemicals

Antineoplastic Agents

Hydroxychloroquine

Cetuximab

Panitumumab

Antineoplastic Agents, Immunological

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Enzyme Inhibitors

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.

Hydroxychloroquine in Combination With Encorafenib and Cetuximab or Panitumumab

Study Coordinator

Devalingam Mahalingam, MD, PhD

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.

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).

* Determine overall survival (OS) by RECIST v1.1 criteria of patients treated with encorafenib, cetuximab or panitumumab, and hydroxychloroquine.
* Determine 'Duration of Response' (DoR) of patients treated with encorafenib, cetuximab or panitumumab, and hydroxychloroquine.
* Determine 'Duration of Stable Disease'(DoSD) of patients treated with encorafenib, cetuximab or panitumumab, and hydroxychloroquine.
* Estimate rates of drug-related toxicities when patients are treated with encorafenib, cetuximab or panitumumab, and hydroxychloroquine.

OUTLINE:

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.

After completion of study treatment, patients are followed up every 3 months (+/- 1 month) for the next 18 months.

Hydroxychloroquine in Combination With Encorafenib and Cetuximab or Panitumumab in the Treatment of Metastatic BRAF-mutated Colorectal Cancer Refractory

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

To determine the ORR by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 criteria for the combination of encorafenib, cetuximab, and hydroxychloroquine. This will be assessed based on RECIST1.1 criteria by cross-sectional imaging done every 2 cycles.

To determine PFS by RECIST v1.1 criteria, with encorafenib, cetuximab, and hydroxychloroquine. Progression is defined as either radiological progression (with CT scan) OR clinical progression.

Determine overall survival (OS) by using RECIST v1.1 criteria. Overall survival time is defined as the time that elapses between C1D1 (start of E+C treatment) and the date of death from any cause.

The evaluation of DoR of patients will be calculated as the time elapsed from the day when 'complete response (CR)' or 'partial response (PR)' is first observed.

Confirmation of response for CR or PR will be conducted via imaging.

Duration of stable disease will be calculated as the time elapsed from the day when "stable disease" is first observed until the earlier of the day of first documented disease progression (clinical OR radiological) using imaging.

To determine safety and tolerability of encorafenib, cetuximab, and hydroxychloroquine as determined by NCI CTCAE v 5.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Hydroxychloroquine in Combination With Encorafenib and Cetuximab or Panitumumab in the Treatment of Metastatic BRAF-mutated Colorectal Cancer Refractory	NCT05576896	Stage IV Colore... Colorectal Canc... Colorectal Canc...	Hydroxychloroqu...	18 Years -	Northwestern University
Hydroxychloroquine in Combination With Encorafenib and Cetuximab or Panitumumab in the Treatment of Metastatic BRAF-mutated Colorectal Cancer Refractory	NCT05576896	Stage IV Colore... Colorectal Canc... Colorectal Canc...	Hydroxychloroqu...	18 Years -	Northwestern University

Spots Global Cancer Trial Database for stage iv colorectal cancer positive for braf v600e mutation