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

This study has been completed.
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Eunice L. Kwak, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00593060
First received: December 28, 2007
Last updated: December 1, 2011
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Colorectal Adenocarcinoma
Drug: Temsirolimus
Drug: Cetuximab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Temsirolimus (CCI-779, Torisel) Combined With Cetuximab (Erbitux) in Cetuximab-Refractory Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • To determine the dose-limiting toxicities and maximal tolerated doses of cetuximab combined with temsirolimus. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • To determine the dosing regimen appropriate for Phase 2 studies of the combination. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To determine the pharmacokinetics of combined treatment with cetuximab and temsirolimus. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To document objective response rate and progression-free survival in patients treated with the combination. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: October 2007
Study Completion Date: October 2010
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
    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.
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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00593060

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Massachusetts General Hospital
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
Principal Investigator: Eunice Kwak, MD, PhD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Eunice L. Kwak, MD, PhD, Assistant in Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00593060     History of Changes
Other Study ID Numbers: 07-172
Study First Received: December 28, 2007
Last Updated: December 1, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Temsirolimus
cetuximab
metastatic disease

Additional relevant MeSH terms:
Colorectal Neoplasms
Adenocarcinoma
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Cetuximab
Sirolimus
Everolimus
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 01, 2014