Encorafenib for BRAF V600E-mutant Metastatic Colorectal Cancer

Phase-Based Progress Estimates
2
Effectiveness
3
Safety
Rocky Mountain Lions Eye Institute, Aurora, CO
BRAF V600E-mutant Metastatic Colorectal Cancer+1 More
Encorafenib - Drug
Eligibility
18+
All Sexes
What conditions do you have?
Select

Study Summary

This study is evaluating whether a new drug combination can improve the survival of people with metastatic colorectal cancer.

See full description

Eligible Conditions

  • BRAF V600E-mutant Metastatic Colorectal Cancer

Treatment Effectiveness

Effectiveness Progress

2 of 3
This is further along than 85% of similar trials

Other trials for BRAF V600E-mutant Metastatic Colorectal Cancer

Study Objectives

This trial is evaluating whether Encorafenib will improve 5 primary outcomes and 56 secondary outcomes in patients with BRAF V600E-mutant Metastatic Colorectal Cancer. Measurement will happen over the course of Cycle 1 (up to 28 days).

Day 1
(Phase 3) Evaluation of the Model-Based Clearance (CL) for Cetuximab
(Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Binimetinib
(Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Encorafenib
Day 28
(Safety Lead-in) Number of Participants With Dose-limiting Toxicities (DLTs)
Month 6
(Phase 3) Change From Baseline in the EuroQol-5D-5L (EQ-5D-5L) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet
(Phase 3) Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30) Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet
(Phase 3) Change From Baseline in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet
(Phase 3) Change From Baseline in the Patient Global Impression of Change (PGIC) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet
(Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per BICR
(Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per Investigator
(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per BICR
(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per Investigator
(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by BICR
(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by Investigator
(Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per BICR
(Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per Investigator
(Phase 3) Comparison of Progression-free Survival (PFS) in Doublet Arm vs Control Arm Per BICR
(Phase 3) Comparison of Progression-free Survival (PFS) in Doublet Arm vs Control Arm Per Investigator
(Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Control Arm Per BICR
(Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Control Arm Per Investigator
(Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Doublet Arm Per BICR
(Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Doublet Arm Per Investigator
(Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per BICR
(Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per Investigator
(Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per BICR
(Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per Investigator
(Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per BICR
(Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per Investigator
(Phase 3) Overall Survival (OS) in Doublet Arm vs. Control Arm
(Phase 3) Overall Survival (OS) in Triplet Arm vs. Doublet Arm
(Phase 3) Overall Survival (OS) of Triplet Arm vs. Control Arm
(Phase 3) Response Rate (ORR) by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors (RECIST), v1.1 of Triplet Arm vs. Control Arm
Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Control Arm Per Investigator
Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per BICR
Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per Investigator
Month 6
(Safety Lead-in) Duration of Response (DOR) by BICR
(Safety Lead-in) Duration of Response (DOR) by Investigator
(Safety Lead-in) Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs)
(Safety Lead-in) Number of Participants With Adverse Events (AEs)
(Safety Lead-in) Progression-free Survival (PFS) by BICR
(Safety Lead-in) Progression-free Survival (PFS) by Investigator
(Safety Lead-in) Response Rate (ORR) by BICR
(Safety Lead-in) Response Rate (ORR) by Investigator
(Safety Lead-in) Time to Response by BICR
(Safety Lead-in) Time to Response by Investigator
Day 1
(Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve (AUC) for Binimetinib
(Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve (AUC) for Cetuximab
(Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve (AUC) for Encorafenib
(Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve (AUC) for Metabolite of Binimetinib (AR00426032)
(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Binimetinib
(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Cetuximab
(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Encorafenib
(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Metabolite of Binimetinib (AR00426032)
(Safety Lead-in) Evaluation of the Steady-state Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Binimetinib
(Safety Lead-in) Evaluation of the Steady-state Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Cetuximab
(Safety Lead-in) Evaluation of the Steady-state Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Encorafenib
(Safety Lead-in) Evaluation of the Steady-state Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for a Metabolite of Binimetinib
(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Binimetinib
(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Cetuximab
(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Encorafenib
(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Metabolite of Binimetinib (AR00426032)

Trial Safety

Safety Progress

3 of 3
This is further along than 85% of similar trials

Other trials for BRAF V600E-mutant Metastatic Colorectal Cancer

Trial Design

3 Treatment Groups

Control Arm
1 of 3
Doublet Arm
1 of 3
Safety Lead-in, Triplet Arm
1 of 3
Active Control
Experimental Treatment

This trial requires 702 total participants across 3 different treatment groups

This trial involves 3 different treatments. Encorafenib is the primary treatment being studied. Participants will be divided into 2 treatment groups. There is no placebo group. The treatments being tested are in Phase 3 and have had some early promising results.

Doublet ArmEncorafenib + cetuximab.
Safety Lead-in, Triplet ArmEncorafenib + binimetinib + cetuximab.
Control ArmInvestigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Cetuximab
FDA approved
Encorafenib
FDA approved
Binimetinib
FDA approved

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: 2 and 6 hours post-dose on day 1 of cycle 1. predose and 2 hours post-dose on day 1 of cycle 2.
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly 2 and 6 hours post-dose on day 1 of cycle 1. predose and 2 hours post-dose on day 1 of cycle 2. for reporting.

Closest Location

Rocky Mountain Lions Eye Institute - Aurora, CO

Eligibility Criteria

This trial is for patients born any sex aged 18 and older. There are 10 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
Age ≥ 18 years at time of informed consent
Histologically- or cytologically-confirmed CRC that is metastatic
Presence of BRAFV600E in tumor tissue as previously determined by a local assay at any time prior to Screening or by the central laboratory
Progression of disease after 1 or 2 prior regimens in the metastatic setting
Evidence of measurable or evaluable non-measurable disease per RECIST, v1.1
Adequate bone marrow, cardiac, kidney and liver function
Able to take oral medications
Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy from screening through follow-up if of childbearing potential
Males must agree to take appropriate precautions to avoid fathering a child from screening through follow-up
Key

Patient Q&A Section

How many people get colorectal cancer a year in the United States?

"Recent findings shows that CRC affects about 1 million people yearly in the US. Nearly 6,000 CRC patients in the year 2013 will have [colorectal cancer](https://www.withpower.com/clinical-trials/colorectal-cancer)s located in the colon. Cancer Research"

"Aglaia leptocephala\n\nAglaia leptocephala is a species of plant in the family Meliaceae." - Anonymous Online Contributor

Unverified Answer

What causes colorectal cancer?

"There is a strong hereditary component to colorectal cancer, but in the majority of cases, the disease develops in the context of other factors, the most important of which are smoking, stress and infection." - Anonymous Online Contributor

Unverified Answer

What are common treatments for colorectal cancer?

"Therapies for colorectal cancer differ according to whether it is localized (in situ) or has spread (metastatic). Common therapies include surgical staging, chemotherapy, immunotherapy, radiation therapy, and targeted therapies. There is considerable inconsistency regarding use of adjuvant therapies." - Anonymous Online Contributor

Unverified Answer

Can colorectal cancer be cured?

"CRC has a cure rate of 90% in early-stage disease, and an increasing cure rate with further stages of the disease. There is also an increasing cure rate if a proximal colon cancer is encountered. Early detection and a well-planned approach may prevent the disease progressing to a terminal course." - Anonymous Online Contributor

Unverified Answer

What are the signs of colorectal cancer?

"It is common for colorectal cancer to go undetected. Most people (74%) have colorectal cancer symptoms before diagnosis and 80% will have symptoms after surgery and chemotherapy. The most common symptoms are bleeding from the rectum and weight loss. Other symptoms include pain in the gastrointestinal tract, an inability to drink fluids or have bowel movements and a change in bowel habit which may be related to more serious conditions." - Anonymous Online Contributor

Unverified Answer

What is colorectal cancer?

"Although most deaths from [colorectal cancer](https://www.withpower.com/clinical-trials/colorectal-cancer) result from another health condition, roughly 10% of deaths from colorectal cancer are attributable to the cancer itself. The colorectal cancer screening programme in Taiwan is an effective and low-cost way to achieve this goal." - Anonymous Online Contributor

Unverified Answer

What is the average age someone gets colorectal cancer?

"About 40% of colorectal cancers are diagnosed at age 50 or less. This emphasizes the importance of screening for colorectal cancers in patients over age 50." - Anonymous Online Contributor

Unverified Answer

What are the chances of developing colorectal cancer?

"Patients with familial adenomatous polyposis or hereditary non-polyposis colorectal carcinoma have an approximately 20-50% chance of developing [colorectal cancer](https://www.withpower.com/clinical-trials/colorectal-cancer) by age 50. The cumulative risk for persons with microalbuminuria of developing colorectal cancer by age 70 is approximately 5%. People with early onset of colon cancer (patients who have their first cancers before age 45) have a 5-10% chance of development of colorectal cancer by age 70. This information would be useful for patients and their physicians whenever making decisions to screen colon cancer patients more frequently or less frequently." - Anonymous Online Contributor

Unverified Answer

How quickly does colorectal cancer spread?

"This review summarizes the major controversies associated with the staging and grading systems of colorectal cancer and provides new insights about the spread of colorectal cancer." - Anonymous Online Contributor

Unverified Answer

What does encorafenib usually treat?

"There is good evidence that encorafenib is effective in treating patients with advanced [soft tissue sarcoma](https://www.withpower.com/clinical-trials/soft-tissue-sarcoma)s and melanoma. Recent findings provide a basis for further testing it as part of combination therapy for advanced colorectal cancer. Clinically complete response rates are lower than those in advanced sarcomas and melanoma, reflecting the difficulty in obtaining a complete response. It is expected that trials comparing combination therapies incorporating encorafenib alone versus encorafenib with chemotherapy will provide the best evidence as to its role in colon cancer." - Anonymous Online Contributor

Unverified Answer

Has encorafenib proven to be more effective than a placebo?

"Encorafenib was effective in treatment of people with unresectable or metastatic well differentiated colorectal cancer. The high response observed in our study is in keeping with recent data from clinical trials on the molecular targeted agents that have been approved for use in colorectal cancer. Encorafenib showed higher response rates for complete radiologic response than for partial response." - Anonymous Online Contributor

Unverified Answer

What is encorafenib?

"The majority of patients presenting with metastatic colorectal carcinoma experienced a favourable response to the drug. Encorafenib is active in patients with previously treated metastatic colorectal cancer, even in those with a progressive disease history, with good tolerability." - Anonymous Online Contributor

Unverified Answer
Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.
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