What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, such as irinotecan and panitumumab, have a range of side effects. Irinotecan can cause gastrointestinal issues like diarrhea, nausea, and vomiting, as well as hematologic toxicities such as neutropenia. Panitumumab, a monoclonal antibody, may lead to dermatologic toxicities including rash and dry skin, as well as hypomagnesemia. Both treatments can also cause fatigue and infusion-related reactions. These side effects are important considerations for patients undergoing treatment for colorectal cancer.

What prior FDA approvals exist?

The FDA has approved several treatments for colorectal cancer, including chemotherapeutic agents like irinotecan hydrochloride, which works by inhibiting cell division and growth. Monoclonal antibodies such as panitumumab, which target specific proteins on cancer cells, have also been approved. While the glutaminase inhibitor CB-839 is still under investigation, it represents a novel approach by targeting the glutaminase enzyme necessary for tumor cell growth. This investigational drug is being studied in combination with panitumumab and irinotecan hydrochloride, reflecting a trend towards combination therapies that target multiple pathways in cancer treatment.

What other types of research exist?

Promising novel alternatives to Glutaminase Inhibitor CB-839 for colorectal cancer patients include: 1) PI3K/PTEN/AKT/mTOR pathway inhibitors such as temsirolimus and everolimus, which have shown potential in inhibiting tumor growth and improving clinical outcomes. 2) Monoclonal antibodies like panitumumab, which target specific proteins on cancer cells to inhibit their growth and spread. 3) Combination therapies involving irinotecan hydrochloride, which is a chemotherapy agent that works by stopping cancer cell division and growth. These alternatives offer different mechanisms of action and may provide effective treatment options for colorectal cancer patients.

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Glutaminase Inhibitor

CB-839 + Panitumumab + Irinotecan for Colorectal Cancer

Phase 1 & 2

Waitlist Available

Led By Jordan Berlin, MD

Research Sponsored by Vanderbilt-Ingram Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Serum creatinine =< 2 mg/dL, or calculated creatinine clearance > 50 mL/min (per the Cockcroft-Gault formula)

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Must not have

Unable to receive oral medication

Active inflammatory bowel disease, other bowel disease causing chronic diarrhea (defined as > 4 loose stools per day), or bowel obstruction

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 12 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug (CB-839) combined with two other drugs to treat advanced colorectal cancer that hasn't responded to other treatments. The new drug blocks enzymes needed for cancer growth, while the other drugs prevent the spread of cancer and kill the cancer cells.

Who is the study for?

This trial is for adults with metastatic RAS wildtype colorectal cancer that's resistant to treatment. They must be in good physical condition, have certain blood and organ function levels, and not be pregnant or breastfeeding. Participants need to agree to use contraception and some will undergo biopsies and PET scans.

What is being tested?

The trial tests CB-839 (a glutaminase inhibitor) combined with panitumumab (an antibody) and sometimes irinotecan hydrochloride (chemotherapy). It aims to find the best dose, understand side effects, and see how well these treatments work together against advanced colorectal cancer.

What are the potential side effects?

Potential side effects include reactions related to immune system activation by monoclonal antibodies like panitumumab, chemotherapy-related issues such as nausea or hair loss from irinotecan hydrochloride, and any unknown risks from the new drug CB-839.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My kidney function is normal or only slightly impaired.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My colorectal cancer is confirmed to be KRAS wildtype and has spread.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I cannot take medicine by mouth.

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I have an active bowel condition causing chronic diarrhea or obstruction.

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I experienced severe side effects from irinotecan treatment.

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I have or had lung scarring or inflammation.

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I have Gilbert's disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 12 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum Tolerated Dose (Phase I) of CB-839 in Combination With Panitumumab and Irinotecan Hydrochloride

Recommended Phase 2 Dose of CB-839 in Combination With Panitumumab and Irinotecan Hydrochloride (Phase I)

Response Rate (Phase II)

Secondary study objectives

Coefficient of Determination (R2) of Maximum Standardized Uptake Value (SUVmax) of Fluorine F 18 L-glutamate Derivative BAY94-9392 (18F-FSPG) Uptake Change With Tumor Size Change (Phase II)

Disease Control Rate

Overall Survival

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Panitumumab/Irinotecan/CB-839Experimental Treatment6 Interventions

Patients receive glutaminase inhibitor CB-839 PO BID on days 1-28, panitumumab IV over 60-90 minutes on days 1 and 15, and irinotecan hydrochloride IV over 90 minutes on day 1 and 15 (Phase I only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Irinotecan Hydrochloride (phase I only)

2017

Completed Phase 2

~30

Imaging with 11C-Glutamine PET/CT scans and 18F-FSPG PET/CT scans

2017

Completed Phase 2

~30

Glutaminase Inhibitor CB-839

2017

Completed Phase 2

~60

Panitumumab

2017

Completed Phase 3

~7150

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for colorectal cancer include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy drugs, such as irinotecan, work by killing rapidly dividing cancer cells or stopping their division. Targeted therapies, like panitumumab, interfere with specific molecules involved in tumor growth and progression. Glutaminase inhibitors, such as CB-839, block the glutaminase enzyme, which is essential for tumor cell metabolism and growth. Immunotherapy harnesses the body's immune system to recognize and destroy cancer cells. These treatments are crucial for colorectal cancer patients as they offer multiple strategies to inhibit tumor growth, improve survival rates, and potentially reduce the side effects associated with traditional chemotherapy.

Glutamine modulates phenotype and stimulates proliferation in human colon cancer cell lines.Ameliorative Potential of L-Alanyl L-Glutamine Dipeptide in Colon Cancer Patients Receiving Modified FOLFOX-6 Regarding the Incidence of Diarrhea, the Treatment Response, and Patients' Survival: A Randomized Controlled Trial.Combination Compositions Composed of l-Glutamine and Si-Jun-Zi-Tang Might Be a Preferable Choice for 5-Fluorouracil-Induced Intestinal Mucositis: An Exploration in a Mouse Model.