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

Primary Purpose

Colorectal Cancer, Colorectal Adenocarcinoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Temsirolimus
Cetuximab
Sponsored by
Jeffrey W. Clark, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring Temsirolimus, cetuximab, metastatic disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital
  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Temsirolimus Combined With Cetuximab

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

To document objective response rate and progression-free survival in patients treated with the combination.

Full Information

First Posted
December 28, 2007
Last Updated
May 23, 2023
Sponsor
Jeffrey W. Clark, MD
Collaborators
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Wyeth is now a wholly owned subsidiary of Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT00593060
Brief Title
Temsirolimus (CCI-770, Torisel) Combined With Cetuximab in Cetuximab-Refractory Colorectal Cancer
Official Title
A Phase I Trial of Temsirolimus (CCI-779, Torisel) Combined With Cetuximab (Erbitux) in Cetuximab-Refractory Colorectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
November 1, 2007 (Actual)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
November 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jeffrey W. Clark, MD
Collaborators
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Wyeth is now a wholly owned subsidiary of Pfizer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Colorectal Adenocarcinoma
Keywords
Temsirolimus, cetuximab, metastatic disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Temsirolimus Combined With Cetuximab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Temsirolimus
Other Intervention Name(s)
Torisel, CCI-779
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
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.
Primary Outcome Measure Information:
Title
To determine the dose-limiting toxicities and maximal tolerated doses of cetuximab combined with temsirolimus.
Time Frame
2 years
Title
To determine the dosing regimen appropriate for Phase 2 studies of the combination.
Time Frame
2 years
Title
To determine the pharmacokinetics of combined treatment with cetuximab and temsirolimus.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
To document objective response rate and progression-free survival in patients treated with the combination.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey W Clark, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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