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

NCT00512798 | Terminated Phase 1 Results DMC

• 3 other identifiers: VICC PHI 0241VU-VICC-PHI-0241VU-VICC-IRB-020510
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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)

Outcome Measures

Primary Outcomes (2)

• Optimal Doses of Temozolomide and Bortezomib (Phase I)

  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

  up to 42 days

• Number of Patients With Clinical Anti-tumor Activity Phase II)

  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

  every 9 weeks to a maximum of 54 weeks

Secondary Outcomes (3)

• Patients With Inhibition in NF-kB Activation (Phase I)

  at baseline, on day 8 and on day 29

• Patients With Clinical Anti-tumor Activity (Phase I)

  every 9 weeks up to a maximum of 54 weeks

• Patients With Inhibition of NF-kB (Phase II)

  at baseline, on day 8 and on day 29

Study Arms (2)

Phase I

EXPERIMENTAL

Drug: PS-341 (VELCADE); Drug: temozolomide; Other: immunoenzyme technique

Phase II

EXPERIMENTAL

Drug: PS-341 (VELCADE); Drug: Temozolomide

Interventions

PS-341 (VELCADE) 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

Also known as: bortezomib

Phase I

Temozolomide 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

Also known as: TMZ

Phase I

immunoenzyme technique OTHER

Not noted

Also known as: None noted

Phase I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Melanoma; Brain Neoplasms

Interventions

Bortezomib; Temozolomide; Immunoenzyme Techniques

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dacarbazine; Triazenes; Imidazoles; Azoles; Immunoassay; Immunologic Techniques; Investigative Techniques; Immunohistochemistry; Molecular Probe Techniques

Results Point of Contact

• Title: Jeffrey Sosman, M.D.
• Organization: Vanderbilt-Ingram Cancer Center

jeff.sosman@vanderbilt.edu

Study Officials

• Jeffrey A. Sosman, MD

  Vanderbilt-Ingram Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine; Director, Melanoma and Tumor Immunotherapy Program; Medical Oncologist

Study Record Dates

• First Submitted: August 6, 2007
• First Posted: August 8, 2007
• Study Start: June 1, 2003
• Primary Completion: July 1, 2006
• Study Completion: March 1, 2008
• Last Updated: October 2, 2012
• Results First Posted: August 3, 2012

Record last verified: 2012-09

Locations

US (1)