Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

SB-715992 in Treating Patients With Metastatic or Recurrent Malignant Melanoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 18 and over NCI CAN-NCIC-IND169 NCIC-169, NCT00095953, IND169

Objectives

1. Determine the efficacy of SB-715992, in terms of response rate, in patients with previously untreated metastatic or recurrent malignant melanoma.
2. Determine the toxic effects of this drug in these patients.
3. Determine the early progression rate and response duration in patients treated with this drug.
4. Determine the pharmacokinetics of this drug in these patients.
5. Correlate pharmacokinetics with safety and efficacy endpoints of this drug in these patients.
6. Correlate β-tubulin and kinesin spindle protein expression in tumor tissue with clinical outcomes in patients treated with this drug.

Entry Criteria

Disease Characteristics:

• Histologically confirmed malignant melanoma
  • Previously untreated metastatic or recurrent disease
  • Considered incurable by standard therapies



• Measurable disease
  • At least one unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
  • Bone metastases are not considered measurable disease
  • Outside any previously irradiated area
    • Patients whose sole site of measurable disease is in a previously irradiated area are ineligible unless there is evidence of progression or new lesions documented in the irradiated field



• No known CNS metastases
  • CT scans or MRI are not required to rule out CNS metastases unless patient exhibits neurological signs or symptoms
  • Patients with a prior solitary brain metastasis surgically resected with no evidence of residual disease are eligible provided CT scan or MRI confirms no evidence of disease within the past 28 days



• Archival paraffin tumor specimen available

Prior/Concurrent Therapy:

Biologic therapy

• At least 3 months since prior adjuvant immunotherapy
• No prior immunotherapy for metastatic or recurrent disease

Chemotherapy

• No prior chemotherapy, including regional therapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy except for low-dose, non-myelosuppressive radiotherapy

Surgery

• See Disease Characteristics
• At least 4 weeks since prior major surgery

Other

• More than 28 days since prior investigational agents
• More than 14 days since prior and no concurrent use of any of the following CYP3A4 inhibitors or inducers:
  • Clarithromycin
  • Erythromycin
  • Troleandomycin
  • Itraconazole
  • Ketoconazole
  • Fluconazole (≤ 200 mg/day allowed)
  • Voriconazole
  • Nefazodone
  • Fluvoxamine
  • Verapamil
  • Diltiazem
  • Grapefruit juice
  • Bitter orange
  • Phenytoin
  • Carbamazepine
  • Phenobarbital
  • Oxcarbazepine
  • Rifampin
  • Rifabutin
  • Rifapentine
  • Hypericum perforatum (St. John's wort)
  • Modafinil
• At least 6 months since prior and no concurrent amiodarone
• No concurrent antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer treatment
• No other concurrent investigational therapies

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³

Hepatic

• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumors with no evidence of disease for ≥ 5 years
• No other uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study participation
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to SB-715992

Expected Enrollment

A total of 15-25 patients will be accrued for this study within 12-14 months.

Outcomes

Response

Toxicity
Pharmacokinetics at day 1 of course 1 (day 1 of course 2 if dose is changed)
Molecular correlates on archival tissue, fresh tumor tissue, and peripheral blood mononuclear cells (PVMCs)

Outline

This is a nonrandomized, multicenter study.

Patients receive SB-715992 IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

All patients are followed at 4 weeks after completion of protocol therapy. Patients with ongoing complete response, partial response, or stable disease are followed every 3 months thereafter until relapse.

Lee CW, Bélanger K, Rao SC, et al.: A phase II study of ispinesib (SB-715992) in patients with metastatic or recurrent malignant melanoma: a National Cancer Institute of Canada Clinical Trials Group trial. Invest New Drugs 26 (3): 249-55, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

NCIC-Clinical Trials Group

Christopher Lee, MD, Protocol chair		Ph: 604-930-2098 Email: clee@bccancer.bc.ca

Registry Information
Official Title		A Phase II Study of SB-715992 (NSC 727990) in Previously Untreated Patients With Metastatic or Recurrent Malignant Melanoma
Trial Start Date		2004-11-22
Registered in ClinicalTrials.gov		NCT00095953
Date Submitted to PDQ		2004-09-15
Information Last Verified		2006-05-30
NCI Grant/Contract Number		CM17107