Doxil, Gemcitabine, and Velcade (PS341) in Advanced Cancer Patients - Full Text View

Sponsored by:	M.D. Anderson Cancer Center
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00500422

Purpose

Primary objective:

To determine the maximum tolerated dose of a combination of Doxil, gemcitabine and PS341 (Velcade).
To determine the qualitative and quantitative toxicity and safety of this combination.

Secondary objective:

To document in a descriptive fashion, responses to this combination.

Condition	Intervention	Phase
Solid Tumors	Drug: Doxil Drug: Gemcitabine Drug: Velcade	Phase I

MedlinePlus related topics: Cancer

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Gemcitabine hydrochloride Gemcitabine Bortezomib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase I Study of a Combination of Doxil, Velcade, and Gemcitabine in Advanced Cancer

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

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. [ Time Frame: 9 Years ] [ Designated as safety issue: No ]
To study the effect of this combination treatment on tumor growth. [ Time Frame: 9 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	216
Study Start Date:	January 2005
Estimated Primary Completion Date:	April 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Doxil + Gemcitabine + Velcade	Drug: Doxil Starting dose of 20 mg/m^2 IV over 2 hours on Day 1, 21 day cycle Drug: Gemcitabine 500 mg/m^2 IV over 30 minutes on Days 1 and 8, 21 day cycle 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

Detailed Description:

Pegylated liposomal doxorubicin (Doxil) 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 (Velcade) is a new drug that is designed to block the proteins needed for tumor growth.

Before you can start treatment on the study, you will have what are called "screening tests". These tests will help the doctor decide if you are eligible to take part in the study. You will have a physical exam, including routine blood tests (about 2 tablespoons of blood) and an electrocardiogram (ECG - test to measure the electrical activity of the heart). Women who are able to have children must have a negative pregnancy test. You will have a scan that determines the strength of your heart, x-rays, and other scans such as MRIs and CT scans that measure tumor size. These will be done to measure the tumor.

Groups of 3 participants that are less than 65 years old and 3 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. 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.

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 216 patients will take part in this study. All will be enrolled at M. D. Anderson.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

All patients with histologic proof of advanced cancer, who are not candidates for known regimens or protocol treatments of higher efficacy or priority, shall be eligible for this study unless the standard therapy includes one or more of the drugs in this protocol.
Estimated life expectancy of at least 12 weeks (performance status of less than or equal to 2 (Zubrod scale)).
Patients must voluntarily sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of the hospital. The only acceptable consent form is the one attached at the end of this protocol.
Measurable disease.
No previous chemotherapy or radiotherapy for 3 weeks prior to entering study.
Adequate bone marrow function (ANC > 1,500 and platelet > 100,000) except in the post-transplant arm where the hematologic minimum requirements will not apply if there is disease infiltration of the bone marrow.
Adequate liver function (bilirubin of less than or equal to 1.5 mg%, SGPT or SGOT < 3x normal).
Adequate renal function (creatinine less than or equal to 1.5 mg%).
Cardiac ejection fraction greater than or equal to 50% without evidence of CHF.
Female subject is either post-menopausal or surgically sterilized, or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
Male subject agrees to use an acceptable methods for contraception of the duration of the study.

Exclusion Criteria:

Symptomatic or untreated brain metastases requiring concurrent treatment, inclusive of but not limited to, surgery, radiation, or cortic steroids.
Need for concurrent radiotherapy or other chemotherapy.
New York Heart Association Class > II.
Diagnosis of leukemia or myelodysplastic syndrome.
Prior cumulative doxorubicin dose > 300 mg/m2. Total cumulative dose of doxorubicin plus Doxil should not exceed 550 mg/m2 (or 400 mg/m2).
Pregnant or lactating women. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening.
Patient has greater than or equal to Grade 2 peripheral neuropathy within 14 days before enrollment.
Concurrent infection requiring intravenous antibiotics.
Patient has hypersensitivity to bortezomib, boron, mannitol, doxorubicin, or gemcitabine.
Patient has received other investigational drugs within 14 days before enrollment.
Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00500422

Contacts

Contact: Razelle Kurzrock, MD

713-794-1226

Locations

United States, Texas
U.T.M.D. Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Razelle Kurzrock, MD

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

Razelle Kurzrock, MD

U.T.M.D. Anderson Cancer Center

More Information

UT MD Anderson Cancer Center This link exits the ClinicalTrials.gov site

Responsible Party:	U.T.M.D. Anderson Cancer Center ( Razelle Kurzrock, MD/Professor )
Study ID Numbers:	2003-1002
Study First Received:	July 10, 2007
Last Updated:	October 27, 2008
ClinicalTrials.gov Identifier:	NCT00500422
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Solid Tumors
Doxil
Gemcitabine
Gemzar

Bortezomib
Velcade
PS341

Study placed in the following topic categories:

Bortezomib
Gemcitabine
Doxorubicin

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors

Antibiotics, Antineoplastic
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Protease Inhibitors
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on January 14, 2009