Bortezomib and Temozolomide in Treating Patients With Advanced Refractory Solid Tumors or Melanoma

This study has been terminated.
(This study was terminated due to lack of efficacy)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jeffrey A. Sosman, MD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT00512798
First received: August 6, 2007
Last updated: September 19, 2012
Last verified: September 2012
  Purpose

RATIONALE: Drugs used in chemotherapy, temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or stopping them from dividing. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving temozolomide together with bortezomib may kill more tumor cells.

PURPOSE: To determine the best dose of bortezomib and temozolomide and to see how well they work in treating patients with advanced refractory solid tumors or melanoma.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Melanoma
Solid Tumor
Drug: PS-341 (VELCADE)
Drug: temozolomide
Other: immunoenzyme technique
Drug: Temozolomide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: (Inhibition of NF-kB Signaling in Melanoma Therapy) A Phase I/II Clinical Trial of PS-341, a Proteasome Inhibitor, in Combination With an Extended Continuous Oral Schedule of Temozolomide in Patients With Advanced Refractory Solid Tumors With the Phase II Component Only in Patients With Melanoma

Resource links provided by NLM:


Further study details as provided by Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:
  • Optimal Doses of Temozolomide and Bortezomib (Phase I) [ Time Frame: up to 42 days ] [ Designated as safety issue: No ]
    The optimal biologic dose (OBD) defined as the dose that achieves the greatest degree of inhibition of NF-κB activation in peripheral blood mononuclear cells when co-administered with Temozolomide

  • Number of Patients With Clinical Anti-tumor Activity Phase II) [ Time Frame: every 9 weeks to a maximum of 54 weeks ] [ Designated as safety issue: No ]
    Per RECIST criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions. Patients with CR + PR + SD


Secondary Outcome Measures:
  • Patients With Inhibition in NF-kB Activation (Phase I) [ Time Frame: at baseline, on day 8 and on day 29 ] [ Designated as safety issue: No ]
    Patient with a minimum of 50% reduction from baseline on day 8 or day 29 in NF-kB, measured by picograms/milliliter in peripheral mononuclear blood cells

  • Patients With Clinical Anti-tumor Activity (Phase I) [ Time Frame: every 9 weeks up to a maximum of 54 weeks ] [ Designated as safety issue: No ]
    Per RECIST criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions

  • Patients With Inhibition of NF-kB (Phase II) [ Time Frame: at baseline, on day 8 and on day 29 ] [ Designated as safety issue: No ]
    Patient with a minimum of 50% reduction from baseline on day 8 or day 29 in NF-kB, measured by picograms/milliliter in peripheral mononuclear blood cells


Enrollment: 47
Study Start Date: June 2003
Study Completion Date: March 2008
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I Drug: PS-341 (VELCADE)

Dose Levels PS-341 (day 1)

  • Level -1 0.7 mg/m2
  • Level 1 1.0 mg/m2
  • Level 2 1.0 mg/m2
  • Level 3 1.3 mg/m2
  • Level 4 1.5 mg/m2
Other Name: bortezomib
Drug: temozolomide

Temozolomide (day 8)

  • Level - 1 50 mg/m2
  • Level 1 50 mg/m2
  • Level 2 75/mg/m2
  • Level 3 75 mg/m2
  • Level 4 75 mg/m2
Other Name: TMZ
Other: immunoenzyme technique
Not noted
Other Name: None noted
Experimental: Phase II Drug: PS-341 (VELCADE)
1.3 mg/m2 by IV on days 1, 4, 8, and 11 of every 21 days
Drug: Temozolomide
75 mg/m2 by mouth, daily, during weeks 2-8 (42 days) of every 9-week course.

  Eligibility

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

Inclusion Criteria - for Phase I

  • Histologically proven malignancy (confirmed by Vanderbilt pathologists), advanced non-hematologic malignancy that is not curable by standard surgery, radiation therapy, or chemotherapy. Patients with melanoma, especially those with accessible tumors will be sought for this trial, but this part of the trial will not be limited to only melanoma patients
  • No available effective therapy (ie; therapy known to be curative, to prolong survival, to reduce tumor-related symptoms, or to have a tangible, beneficial effect upon the patient)
  • Adequate performance status for the study, Eastern Cooperative Oncology Group (ECOG) 0-1
  • Adequate baseline organ system function, usually:

    • Absolute neutrophil count > or equal to 1500/uL
    • Hemoglobin > or equal to 9.0g/dL
    • Platelet count > or equal to 100,000/uL
    • Institutional Normalized Ratio (INR) < 1.5 prior to any invasive biopsy of tumor tissue
    • Creatinine < or equal to 1.5x institutional upper limit of normal (IULN) (this may be adjusted for drugs totally dependent upon or independent of renal clearance)
    • Aspartate and alanine aminotransferase < or equal to 2.5x IULN, bilirubin < or equal to 1.5x IULN
  • Agreement to use a barrier method of contraception, if potentially fertile
  • Ability to understand and willingness to grant informed consent
  • Patients with brain metastases are eligible only if the brain lesions are under control for a minimum of 4 weeks, with no progressive symptoms, and off systemic steroids. Patients with primary brain tumors are eligible if their dose of systemic steroids is stable for at least 5 days.
  • Completed prior chemotherapy a minimum of 4 weeks previously (6 weeks for BCNU and/or mitomycin C), 4 weeks for prior biologic therapy, and 2 weeks for localized radiation therapy. All treatment related toxicity must have resolved as well. Patients can not receive concomitant radiation therapy
  • Patients must be 18 years of age or above and competent to sign an institutionally Institutional Review Board approved informed consent

Exclusion Criteria - for Phase I

  • Patients with Grade 2 or greater peripheral neuropathy
  • Above a maximum of 320 mg/m2 of CDDP for lifetime previously administered would make patient ineligible. No prior taxanes.
  • Uncontrolled or serious infection
  • New York Heart Association Class III or IV heart disease or uncontrolled angina
  • Myocardial infarction, cerebrovascular accident, or pulmonary embolism within the past 6 months
  • Concurrent therapy for cancer
  • Inability to comply with protocol-specified procedures (ie, treatment, monitoring, or follow-up)

Inclusion Criteria - for Phase II

  • For the phase II trial, all patients must have advanced and incurable melanoma. Disease must be measurable. Histologic proof of disease past the primary site
  • No other active malignancy including solid tumors or hematologic cancers within 24 months other than CIS, non-melanoma skin cancer, DCIS of breast, and melanoma in situ
  • Melanoma patients can have up to 2 regimens of prior biologic therapies and a single regimen of systemic chemotherapy for disseminated disease.. Chemotherapy is allowed only in the chemotherapy treated patients cohort. Prior TMZ or DTIC is only allowed in those patients enrolled into the prior chemotherapy cohort
  • All patients must have ECOG 0-1.
  • Adequate baseline organ system function, usually:

    • Absolute neutrophil count > or equal to 1500/uL
    • Hemoglobin > or equal to 9.0g/dL
    • Platelet count > equal to 100,000/uL
    • INR < 1.5 prior to any invasive biopsy of tumor tissue
    • Creatinine < or equal to 1.5x institutional upper limit of normal (IULN) (this may be adjusted for drugs totally dependent upon or independent of renal clearance)
    • Aspartate and alanine aminotransferase < or equal to 2.5x IULN, bilirubin < or equal to 1.5x IULN
  • Completed prior chemotherapy a minimum of 4 weeks previously (6 weeks for BCNU and/or mitomycin C), 4 weeks for prior biologic therapy, and 2 weeks for localized radiation therapy. No prior PS-341 is allowed. All treatment related toxicity must have resolved as well. Patients can not receive concomitant radiation therapy. Prior TMZ or DTIC is only allowed in those patients enrolled into the prior chemotherapy cohort
  • Patients must be 18 years of age or above and competent to sign an institutionally IRB approved informed consent.

Exclusion criteria - for Phase II

  • Patients with Grade 2 or greater peripheral neuropathy.
  • Uncontrolled or serious infection requiring parenteral antibiotics
  • New York Heart Association Class III or IV heart disease or uncontrolled angina
  • Myocardial infarction, cerebrovascular accident, or pulmonary embolism within the past 6 months
  • Concurrent therapy for cancer xiii. Inability to comply with protocol-specified procedures (ie, treatment, monitoring, or follow-up)
  • Patients with brain metastases are ineligible unless the lesions have been resected or irradiated a minimum of 2 months prior to treatment, be off of steroids, and show no evidence for active disease on MRI,
  • Above a maximum of 320 mg/m2 of CDDP for lifetime previously administered would make patient ineligible. No prior taxanes
  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: NCT00512798

Locations
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Investigators
Study Chair: Jeffrey A. Sosman, MD Vanderbilt-Ingram Cancer Center
  More Information

No publications provided

Responsible Party: Jeffrey A. Sosman, MD, Professor of Medicine; Director, Melanoma and Tumor Immunotherapy Program; Medical Oncologist, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT00512798     History of Changes
Obsolete Identifiers: NCT00209248
Other Study ID Numbers: VICC PHI 0241, VU-VICC-PHI-0241, VU-VICC-IRB-020510
Study First Received: August 6, 2007
Results First Received: June 27, 2012
Last Updated: September 19, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt-Ingram Cancer Center:
stage III melanoma
stage IV melanoma
recurrent melanoma
unspecified adult solid tumor, protocol specific
recurrent adult brain tumor
melanoma (skin)

Additional relevant MeSH terms:
Melanoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms by Site
Nervous System Diseases
Temozolomide
Dacarbazine
Bortezomib
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014