A Combination of Zarnestra With Velcade for Patients With Relapsed Multiple Myeloma

This study has been terminated.
(Initial Principal Investigator left Moffitt)
Sponsor:
Collaborators:
Millennium Pharmaceuticals, Inc.
Information provided by:
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00361088
First received: August 3, 2006
Last updated: November 21, 2013
Last verified: May 2011
  Purpose

In Phase I, patients will receive a combination of PS-341 (Velcade) and R115777 (Zarnestra) to determine the dose limiting toxicity (DLT). Once DLT is determined, patients in Phase II will be receive the maximum tolerated dose (MTD) to complete 8 cycles of therapy. Treatment will continue if there is evidence of continued response for 8 cycles. Patients will receive follow up to include normal laboratory evaluations at least every 3 months and a skeletal survey will be performed at least every 6 months.


Condition Intervention Phase
Multiple Myeloma
Drug: PS-341
Drug: R11577
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Dose Escalation of Zarnestra (R115777) Combined With Velcade® (PS-341) in Patients With Relapsed Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Dose Limiting Toxicity (DLT) [ Time Frame: Average of 6 months ] [ Designated as safety issue: No ]
    Determine the dose limiting toxicity at 3 weeks post treatment

  • Maximum Tolerated Dose [ Time Frame: Average of 6 months ] [ Designated as safety issue: No ]
    Determine the maximum tolerated dose

  • Response Rates [ Time Frame: Average of 6 months ] [ Designated as safety issue: No ]
    Determine response rates after 8 cycles of treatment

  • Toxicity [ Time Frame: Average of 6 months ] [ Designated as safety issue: Yes ]
    Determine toxicity profiles


Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: Average of 12 months ] [ Designated as safety issue: No ]
    Determine progression free survival


Enrollment: 42
Study Start Date: August 2005
Study Completion Date: June 2007
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I Drug: PS-341
Phase I and II: 1.3mg/m2 iv days 1,4,8,11
Other Names:
  • bortezomib
  • Velcade®
Drug: R11577

Phase I: 100mg po BID days 1014 for Cohort 1, 200mg po BID days 1014 for Cohort 2, 300mg po BID days 1014 for Cohort 3.

Phase II: Maximum Tolerated Dose (MTD)

Other Name: Zarnestra
Experimental: Phase II Drug: PS-341
Phase I and II: 1.3mg/m2 iv days 1,4,8,11
Other Names:
  • bortezomib
  • Velcade®
Drug: R11577

Phase I: 100mg po BID days 1014 for Cohort 1, 200mg po BID days 1014 for Cohort 2, 300mg po BID days 1014 for Cohort 3.

Phase II: Maximum Tolerated Dose (MTD)

Other Name: Zarnestra

Detailed Description:

In Phase I, patients will receive intravenous PS-341 (Velcade) and 3 different dose levels of oral R115777 (Zarnestra). Dose Limiting Toxicity (DLT) will be determined over a period of one cycle and dose escalation to the next level will not occur until all patients projected at each level complete one cycle of therapy. Once DLT is determined, patients in Phase I and all patients enrolled for the phase II component will be treated at the maximum tolerated dose (MTD) to complete 8 cycles of therapy. Treatment will continue beyond 8 cycles if there is evidence of continued response. The study regimen will consist of two weeks of treatment followed by one week off for a total cycle duration of three weeks. If disease stabilization occurs (noted on 2 consecutive cycles) after the standard 8 cycles are given, treatment will be discontinued.

Patients are to be monitored for adverse events throughout the treatment phases and for a minimum of 30 days after their last dose of drugs. Follow up will include history and physical exam with laboratory evaluation at least every 3 months. Laboratories will include CMP, CBC, SPEP, UPEP, and quantitative immunoglobulins. A skeletal survey will be performed at least every 6 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Voluntary written informed consent
  • Female subject is either post-menopausal/surgically sterilized or willing to use an acceptable method of birth control for the duration of the study.
  • Male subject agrees to use an acceptable method for contraception for the duration of the study.
  • Diagnosis of stage II or III multiple myeloma and have relapsed after at least one prior therapies confirmed by the presence of:

    1. A new lytic lesion
    2. A 25% increase in urine or serum monoclonal protein
  • Patient can have received PS-341 (Velcade) previously and does not require a previous response.
  • Patients must have measurable disease. One or more of the following must be present to qualify for this study:

    1. Serum M-component greater than or equal to 1.0 gm/dl (10.0 g/L) by serum protein electrophoresis
    2. Urine M-protein excretion > 200 mg/24 (0.2 g/24h) hours, by urine protein electrophoresis
    3. Abnormal serum free light chain ratio with elevated Kappa or Lambda light chains in serum
  • Baseline measurements must be done within 21 days of study entry.
  • Karnofsky Performance Status Scale > 60.
  • Greater than or equal to 18 years of age.
  • Expected survival of greater than 8 weeks.
  • Swallow intact study medication tablets.
  • Can follow directions or has a caregiver who will be responsible for administering study medication.

Exclusion Criteria:

  • Previously treated with R115777 (Zarnestra).
  • Undergone an allogeneic bone marrow transplant.
  • A platelet count of <100,000 x 10 to the 9 power/L within 14 days before enrollment.
  • Absolute neutrophil count of <1.0 x 10 to the 9 power/L within 14 days before enrollment.
  • Measured creatinine > 1.5 X the upper limits of normal within 14 days before enrollment.
  • Greater than or equal to Grade 2 peripheral neuropathy within 14 days before enrollment.
  • Hypersensitivity to bortezomib, boron, mannitol or imidazole compounds
  • Female subject is pregnant or breast-feeding. 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.
  • Received other investigational drugs within 14 days of enrollment or immunotherapy within 30 days of enrollment.
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Ongoing radiation therapy or radiation therapy within 14 days prior to first treatment.
  • Cytotoxic chemotherapy within 30 days prior to first treatment.
  • Therapy with high-dose corticosteroids within 14 days prior to first treatment.
  • Presence of any of the following excludes a patient from entering the study until such condition is resolved (determined within 14 days prior to the first treatment):

    1. Elevated total bilirubin > 2mg/dl, or direct bilirubin > 2 times the ULN.
    2. Serum glutamic oxaloacetic transaminase (AST, formerly SGOT) or serum glutamic pyruvic transaminase (ALT, formerly SGPT) > 2 times the ULN
    3. Serum calcium > 12 mg/dL.
    4. Concurrent serious infection.
    5. Life-threatening illness (unrelated to tumor).
  • History of any other ACTIVE and INVASIVE cancer other than the present condition (except non-melanoma skin cancer), unless in complete remission and off of all therapy for that disease for a minimum of 3 years.
  • Prohibited/allowable medications or precautions:

    1. Enzyme-inducing anti-epileptic medications (e.g. phenytoin, phenobarbital, carbamazepine) are not allowed.
    2. Non-enzyme anti-epileptic medications will be allowed.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00361088

Locations
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Melissa Alsina, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Melissa Alsina, H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00361088     History of Changes
Other Study ID Numbers: MCC-13971, 7032
Study First Received: August 3, 2006
Last Updated: November 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Velcade (PS-341)
Bortezomib
Zarnestra (R115777)
Tipifarnib

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Tipifarnib
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 23, 2014