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

NCT ID: NCT00512798

Last Updated: 2012-10-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-30
• Study Completion Date: 2008-03-31

Brief Summary

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.

Conditions

Brain and Central Nervous System Tumors; Melanoma; Solid Tumor

Keywords

stage III melanoma; stage IV melanoma; recurrent melanoma; unspecified adult solid tumor, protocol specific; recurrent adult brain tumor; melanoma (skin)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I

Group Type: EXPERIMENTAL

PS-341 (VELCADE)

Intervention Type: DRUG

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

temozolomide

Intervention Type: DRUG

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

immunoenzyme technique

Intervention Type: OTHER

Not noted

Phase II

Group Type: EXPERIMENTAL

PS-341 (VELCADE)

Intervention Type: DRUG

1.3 mg/m2 by IV on days 1, 4, 8, and 11 of every 21 days

Temozolomide

Intervention Type: DRUG

75 mg/m2 by mouth, daily, during weeks 2-8 (42 days) of every 9-week course.

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

immunoenzyme technique

Not noted

Intervention Type: OTHER

PS-341 (VELCADE)

1.3 mg/m2 by IV on days 1, 4, 8, and 11 of every 21 days

Intervention Type: DRUG

Temozolomide

75 mg/m2 by mouth, daily, during weeks 2-8 (42 days) of every 9-week course.

Intervention Type: DRUG

Other Intervention Names

bortezomib; TMZ; None noted

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• 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)

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey A. Sosman, MD

Professor of Medicine; Director, Melanoma and Tumor Immunotherapy Program; Medical Oncologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey A. Sosman, MD

Role: STUDY_CHAIR

Vanderbilt-Ingram Cancer Center

Locations

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

VU-VICC-PHI-0241

Identifier Type: -

Identifier Source: secondary_id

VU-VICC-IRB-020510

Identifier Type: -

Identifier Source: secondary_id

VICC PHI 0241

Identifier Type: -

Identifier Source: org_study_id

NCT00209248

Identifier Type: -

Identifier Source: nct_alias