Temsirolimus (CCI-770, Torisel) Combined With Cetuximab in Cetuximab-Refractory Colorectal Cancer

May 23, 2023 updated by: Jeffrey W. Clark, MD

A Phase I Trial of Temsirolimus (CCI-779, Torisel) Combined With Cetuximab (Erbitux) in Cetuximab-Refractory Colorectal Cancer

In this study, the investigational drug, temsirolimus, will be combined with cetuximab, a biologic agent used in the treatment of colorectal cancer. Cetuximab in combination with temsirolimus may be more effective in treating advanced colorectal cancer than cetuximab alone. The purpose of this research study is to try to define the highest dose of cetuximab that can be used safely in combination with temsirolimus to treat advanced colorectal cancer that has progressed through standard therapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

  • Because this is a study to determine the highest dose of cetuximab that can be safely given with temsirolimus, groups of 3 participants will be treated at gradually increasing doses of cetuximab. Each group of 3 participants must complete 4 weeks (1 cycle) of treatment before the following group of 3 participants can start treatment at the higher dose.
  • Cetuximab is administered intravenously 7 days before the treatment cycle begins. Participants will receive a cetuximab infusion every week of the treatment cycle (days 1, 8, 15, 22) along with temsirolimus. Temsirolimus is also given intravenously.
  • As a precaution, participants will be pre-medicated with Benadryl/diphenhydramine to help prevent an allergic reaction.
  • During the study participants will have weekly clinical visits. Each clinic visit will last approximately 2-3 hours. During the clinic visit, the following tests and procedures will be performed: Physical exam; vital signs; and blood tests. A CT scan will be performed after every 2 cycles (8 weeks).
  • Pharmacokinetic (PK) blood samples will be taken at various points during the study. For each PK sample, we will take about 1 teaspoon of blood. There will be a total of 22 tubes of blood taken for the PK study.

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Previously treated metastatic colorectal adenocarcinoma, histologically proven. Subjects must have previously received and had evidence of progression on cetuximab, bevacizumab, 5FU, irinotecan, and oxaliplatin, or demonstrated intolerance to those agents (except cetuximab).
  • Measurable disease by RECIST criteria
  • ECOG Performance Status 0 or 1.
  • Male or female, 18 years of age or older.
  • Life expectancy greater than or equal to 12 weeks.
  • At least 2 weeks have elapsed between previous anti-cancer therapy AND resolution of any skin rash related to prior treatment with an epidermal growth factor receptor inhibitor.
  • Lab values within ranges as outlined in protocol

Exclusion Criteria:

  • Diagnosis of second malignancy within the last 3 years, except for adequately treated basal cell carcinoma or squamous cell skin cancer.
  • Ongoing cardiac dysrhythmias of NCI CTCAE grade >/=2, atrial fibrillation, QTc prolongation to >450msec for males and >470 msec for females.
  • Known immunodeficiency disorders or active infections requiring treatment
  • Pregnancy or breastfeeding
  • Brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease
  • Prior radiation therapy or major surgery within 2 weeks of study entry
  • Prior radiation therapy to > 25% of the bone marrow
  • Treatment with other experimental or alternative therapies during the course of the trial
  • History of hypersensitivity to polysorbate or cetuximab

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Temsirolimus Combined With Cetuximab
Drug: Temsirolimus
Given intravenously every week of each 28-day cycle (days 1, 7, 15, 22). Participants can continue to receive study treatment as long at their tumor is responding.
Other Names:
  • Torisel
  • CCI-779
Drug: Cetuximab
One dose is given intravenously 7 days prior to the start of each 28-day cycle, then it is given every week (along with temsirolimus)of each 28-day cycle (on days 1, 7, 15, 22). Participants can continue to receive study treatment as long at their tumor is responding.
Other Names:
  • Erbitux

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To determine the dose-limiting toxicities and maximal tolerated doses of cetuximab combined with temsirolimus.
Time Frame: 2 years
2 years
To determine the dosing regimen appropriate for Phase 2 studies of the combination.
Time Frame: 2 years
2 years
To determine the pharmacokinetics of combined treatment with cetuximab and temsirolimus.
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
To document objective response rate and progression-free survival in patients treated with the combination.
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jeffrey W. Clark, MD

Collaborators

Wyeth is now a wholly owned subsidiary of Pfizer
Dana-Farber Cancer Institute
Brigham and Women's Hospital

Investigators

  • Principal Investigator: Jeffrey W Clark, MD, Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2007

Primary Completion (Actual)

October 1, 2009

Study Completion (Actual)

November 1, 2010

Study Registration Dates

First Submitted

December 28, 2007

First Submitted That Met QC Criteria

December 28, 2007

First Posted (Estimate)

January 14, 2008

Study Record Updates

Last Update Posted (Actual)

May 24, 2023

Last Update Submitted That Met QC Criteria

May 23, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07-172

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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