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

Sponsors and Collaborators:	Massachusetts General Hospital Dana-Farber Cancer Institute Brigham and Women's Hospital Wyeth
Information provided by:	Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00593060

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 I

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Cetuximab CCI 779

U.S. FDA Resources

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

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: TBD ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	October 2007
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Intervention Details:

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.

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

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

Contacts

Contact: Eunice Kwak, MD, PhD

617-643-3415

ekwak@partners.org

Locations

United States, Massachusetts
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Eunice Kwak, MD, PhD
Dana-Farber Cancer Institute	Not yet recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Thomas Abrams, MD

Sponsors and Collaborators

Massachusetts General Hospital

Dana-Farber Cancer Institute

Brigham and Women's Hospital

Wyeth

Investigators

Principal Investigator:

Eunice Kwak, MD, PhD

Massachusetts General Hospital

More Information

Responsible Party:	Massachusetts General Hospital ( Eunice Kwak, MD, PhD )
Study ID Numbers:	07-172
Study First Received:	December 28, 2007
Last Updated:	December 28, 2007
ClinicalTrials.gov Identifier:	NCT00593060
Health Authority:	United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:

Temsirolimus
cetuximab
metastatic disease

Study placed in the following topic categories:

Digestive System Neoplasms
Gastrointestinal Diseases
Cetuximab
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Intestinal Neoplasms

Carcinoma
Digestive System Diseases
Neoplasm Metastasis
Gastrointestinal Neoplasms
Adenocarcinoma
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009