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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00500422
First received: July 10, 2007
Last updated: February 11, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Solid Tumors
Drug: Doxil
Drug: Gemcitabine
Drug: Velcade
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: Dose limiting toxicity assessed during first course (21 days). ] [ Designated as safety issue: Yes ]

Enrollment: 134
Study Start Date: January 2005
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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

Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00500422

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Gerald Falchook, MD,MS UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00500422     History of Changes
Other Study ID Numbers: 2003-1002
Study First Received: July 10, 2007
Last Updated: February 11, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Solid Tumors
Doxil
Adriamycin
Pegylated Liposomal Doxorubicin
Liposomal Doxorubicin
Doxorubicin Hydrochloride
Gemcitabine
Gemzar
Bortezomib
Velcade
PS341
PS-341
LDP-341
MLN341

Additional relevant MeSH terms:
Gemcitabine
Doxorubicin
Liposomal doxorubicin
Bortezomib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014