Doxil, Gemcitabine, and Velcade (PS341) in Advanced Cancer Patients
The goal of this clinical research study is to find the highest safe dose of the drug Velcade (bortezomib) that can be given together with gemcitabine and pegylated liposomal doxorubicin (Doxil) in the treatment of advanced cancer. The effect of this combination treatment on tumor growth will also be studied.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of a Combination of Doxil, Velcade, and Gemcitabine in Advanced Cancer|
- Maximum Tolerated Dose (MTD) [ Time Frame: Dose limiting toxicity assessed during first course (21 days). ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2005|
|Study Completion Date:||November 2012|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Experimental: Doxil + Gemcitabine + Velcade
Doxil Starting dose of 20 mg/m^2 intravenous (IV) over 2 hours on Day 1 and Gemcitabine 500 mg/m^2 IV over 30 minutes on Days 1 and 8; Velcade Starting dose of 0.7 mg/m^2 IV on Days 1 and 8 of first 21 day cycle; increased dose of 1.0 to 1.3 on Days 1, 4, 8, and 11 of subsequent 21 day cycles.
Starting dose of 20 mg/m^2 IV over 2 hours on Day 1, 21 day cycle
Other Names:Drug: Gemcitabine
500 mg/m^2 IV over 30 minutes on Days 1 and 8, 21 day cycle
Other Names:Drug: Velcade
Starting dose of 0.7 mg/m^2 IV on Days 1 and 8 of first 21 day cycle; increased dose of 1.0 to 1.3 on Days 1, 4, 8, and 11 of subsequent 21 day cycles
Pegylated liposomal doxorubicin is a newer form of the common anticancer drug Adriamycin. It is enclosed in liposomes, which are fat particles found normally in the body. This new form is designed to act against cancer cells while causing less damage to normal tissue. Gemcitabine is a drug that has shown to be active in patients with several different cancers including pancreatic cancer, breast cancer, and certain lymphomas. Bortezomib is a new drug that is designed to block the proteins needed for tumor growth.
Groups of 3 participants that are less than 65 years old and 3-6 participants that are at least 65 years old will be enrolled at a time. Each new group will receive a higher dose level than the group before as long as no serious side effects occur.
Once the highest tolerable dose is determined, up to 30 additional patients with small cell cancer or neuroendocrine carcinoma, and up to 30 patients with T cell lymphoma will be treated at that dose.
All participants will receive pegylated liposomal doxorubicin through a vein over about 2 hours. The drug will be given once every 21 days (3 weeks or 1 cycle). Gemcitabine will be given through a vein over 30 minutes on Days 1 and 8 every 21 days. Patients will only receive the combination of both drugs on Day 1; on that day pegylated liposomal doxorubicin will be given before the dose of gemcitabine. Bortezomib will be given by vein on Days 1, 4, 8 and 11 of every 21 days, except for the first group of patients who will receive it on days 1 and 8 only. Participants whose tumors are responding to treatment may continue treatment if their doctor approves for as long as they respond, as long as there are no serious side effects.
Because of a nationwide shortage of pegylated liposomal doxorubicin, you may continue treatment with gemcitabine and bortezomib. If pegylated liposomal doxorubicin becomes available, you may be able to receive it again.
During the study, you will have a weekly blood test (about 2 tablespoons of blood) and a physical exam. X-rays and other scans, such as MRIs and CT scans, will be done at 6 weeks to measure the size of the tumor. Other tests will be done if needed.
The treatment will be stopped if the cancer grows or if severe side effects occur, and other treatments may be offered.
This is an investigational study. All three drugs are approved by the FDA for use against some kinds of cancer. Their use in this study is investigational. Up to 276 patients will take part in this study. All will be enrolled at MD Anderson.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00500422
|United States, Texas|
|UT MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Gerald Falchook, MD,MS||UT MD Anderson Cancer Center|