Doxil, Gemcitabine, and Velcade (PS341) in Advanced Cancer Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00500422
Recruitment Status : Completed
First Posted : July 12, 2007
Last Update Posted : February 13, 2013
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

July 10, 2007
July 12, 2007
February 13, 2013
January 2005
November 2012   (Final data collection date for primary outcome measure)
Maximum Tolerated Dose (MTD) [ Time Frame: Dose limiting toxicity assessed during first course (21 days). ]
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Complete list of historical versions of study NCT00500422 on Archive Site
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Doxil, Gemcitabine, and Velcade (PS341) in Advanced Cancer Patients
Phase I Study of a Combination of Doxil, Velcade, and Gemcitabine in Advanced Cancer
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.

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.

Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Solid Tumors
  • Drug: Doxil
    Starting dose of 20 mg/m^2 IV over 2 hours on Day 1, 21 day cycle
    Other Names:
    • Pegylated Liposomal Doxorubicin
    • Adriamycin
    • Lipsomal Doxorubicin
    • Doxorubicin Hydrochloride
  • Drug: Gemcitabine
    500 mg/m^2 IV over 30 minutes on Days 1 and 8, 21 day cycle
    Other Names:
    • Gemzar
    • Gemcitabine Hydrochloride
  • 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
    Other Names:
    • Bortezomib
    • PS341
    • PS-341
    • LDP-341
    • MLN341
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.
  • Drug: Doxil
  • Drug: Gemcitabine
  • Drug: Velcade
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
November 2012
November 2012   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. All patients with histologic proof of advanced cancer, who are not candidates for known regimens or protocol treatments of higher efficacy or priority or who have no therapy that increases survival by at least 3 months, shall be eligible for this study unless the standard therapy includes one or more of the drugs in this protocol.
  2. Estimated life expectancy of at least 12 weeks. (Performance status of less than or equal to 2 (Zubrod scale).
  3. 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.
  4. Evaluable disease
  5. Patients must have been off all previous chemotherapy or radiotherapy for at least 3 weeks and off all targeted biologic therapies for at least 5 half-lives, whichever is shorter, prior to entering this study. Patients may receive localized palliative radiotherapy immediately before or during treatment.
  6. Adequate bone marrow function (Absolute neutrophil count (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.
  7. Adequate liver function (bilirubin of less than or equal to 1.5 mg%, alanine aminotransferase (SGPT) < 5 times normal)
  8. Adequate renal function (creatinine less than or equal to 1.5 mg%).
  9. Cardiac ejection fraction greater than or equal to 50% without evidence of Congestive heart failure (CHF)
  10. 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.
  11. Male subject agrees to use an acceptable methods for contraception of the duration of the study.

Exclusion Criteria:

  1. Symptomatic brain metastases requiring concurrent treatment, inclusive of but not limited to, surgery, radiation or cortico steroids.
  2. Need for concurrent radiotherapy or other chemotherapy (other than localized palliative radiotherapy)
  3. New York Heart Association Class > II
  4. Diagnosis of leukemia or myelodysplastic syndrome
  5. Prior cumulative doxorubicin dose > 300 mg/m^2. Total cumulative dose of doxorubicin plus Doxil should not exceed 550 mg/m^2 (or 400 mg/m)
  6. 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.
  7. Patient has greater than or equal to Grade 2 peripheral neuropathy within 14 days before enrollment
  8. Concurrent uncontrolled infection requiring intravenous antibiotics
  9. Patient has hypersensitivity to bortezomib, boron, mannitol, doxorubicin, or gemcitabine.
  10. Patient has received other investigational drugs within 14 days before enrollment.
  11. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Sexes Eligible for Study: All
Child, Adult, Senior
Contact information is only displayed when the study is recruiting subjects
United States
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M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
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Principal Investigator: Gerald Falchook, MD,MS UT MD Anderson Cancer Center
M.D. Anderson Cancer Center
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP