Palbociclib and Cetuximab in Metastatic Colorectal Cancer

Colon Cancer Clinical Trial

Official title: Phase II Single-arm Study of the Combination of Palbociclib and Cetuximab in KRAS/NRAS/BRAF Wild-type Metastatic Colorectal Cancer

Status Active, not recruiting

Clinical Trial Summary

This research study is designed to provide a better understanding of study drugs cetuximab (Erbitux®) and palbociclib when used in combination to treat patients with metastatic colon cancer.

Clinical Trial Description

This research study is designed to provide a better understanding of study drugs cetuximab (Erbitux®) and palbociclib when used in combination to treat patients with metastatic colon cancer.

Cetuximab (Erbitux®) is an antibody designed to target a protein called Epidermal Growth Factor Receptor (EGFR). EGFR plays an important role in the growth and survival of colon cancer. Antibodies are proteins that are naturally produced by the immune system and circulate throughout your body to help protect you from disease caused by bacteria, viruses, cancer cells or any foreign or toxic substance. Antibodies work by sticking to and flagging or marking foreign cells or substances so that your body's immune defense system will recognize, attack and remove them. Antibodies help the body rid itself of disease. Antibodies can also be designed in the laboratory to stick to specific parts of cancer cells (or normal cells) to change or block the ways those cells function in your body and to produce a therapeutic anti-cancer effect. Cetuximab (Erbitux®) is an antibody drug approved by the FDA and is commonly used to treat your type of colon cancer.

Palbociclib is an FDA-approved drug for patients with breast cancer. Palbociclib is not FDA-approved for the treatment of colon cancer, and is considered an investigational drug in this research study. Palbociclib targets a protein called CDK4/6 that is a critical part of the cell division and cell growth processes known as "the cell cycle". Laboratory studies have shown that palbociclib inhibits the cell cycle, slows or stops cell growth, and can cause cell death in cancer cells.

The combination of Cetuximab (Erbitux®) with palbociclib is not approved by the FDA for treating colon cancer and is considered investigational in this research study.

You are being asked to be in the study because your colon cancer has been found to contain the proteins KRAS, NRAS and BRAF that are normal (wild-type). These proteins play an important role in the growth and survival of colon cancer. This requirement is important because colon cancer with these characteristics has been shown to be more responsive to EGFR inhibitors such as cetuximab (Erbitux®), one of the drugs used in this study that is also a standard treatment option for your type of cancer. Also, Epidermal Growth Factor Receptor (EGFR) has been shown to stimulate cancer cell division, growth and survival by working together with KRAS, NRAS and BRAF to activate CDK4/6 and to support an accelerated cell cycle. This accelerated cell cycle allows the cancer cells to divide and grow faster than your normal cells but also can make them sensitive to the effects of CDK4/6 inhibitor palbociclib, a cell-cycle inhibitor.

To participate in this study you also must meet one of the following requirements:

A. You have not been treated with EGFR inhibitors such as cetuximab (Erbitux®) or panitumumab (Vectibix®).

B. You were treated with anti-EGFR drugs such as cetuximab (Erbitux®) or panitumumab (Vectibix®) and experienced at least 4 months of response to treatment, and it has been at least 8-weeks since you were last treated with an anti-EGFR drug.

This will allow investigators to compare the anti-cancer effects of cetuximab (Erbitux®) combined with palbociclib in 2 different groups of cancer patients:

1. Patients that have never received EGFR inhibitors like cetuximab (Erbitux®) or panitumumab (Vectibix®). This group will test whether resistance to the combination of cetuximab (Erbitux®) plus palbociclib develops in this type of cancer.

2. Patients that have previously shown an anti-cancer response to EGFR inhibitors, such as cetuximab (Erbitux®) or panitumumab (Vectibix®), of four or more months, but then developed resistance. This group will test whether the combination of cetuximab (Erbitux®) plus palbociclib is more effective against this resistant type of cancer.

Furthermore, laboratory studies have shown that the combination of EGFR and CDK inhibitors provide a stronger anti-cancer effect when used in combination than seen when each inhibitor is used alone. Thus, the reason researchers are using cetuximab (Erbitux®) and palbociclib in combination is to simultaneously target and inhibit multiple processes inside of the cancer cell that are critical to growth and survival of the tumor. With this combination strategy, researchers hope to improve upon existing anti-cancer therapies. ;

Related Conditions & MeSH terms

• Cancer of the Colon
• Colon Cancer
• Colon Neoplasms
• Colonic Cancer
• Colonic Neoplasms
• Neoplasms
• Neoplasms, Colonic

• NCT number: NCT03446157
• Study type: Interventional
• Source: UNC Lineberger Comprehensive Cancer Center
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 13, 2018
• Completion date: January 26, 2026