Official Title: “A Phase I/II Study of High-Dose Calcitriol in Combination With Temozolomide for Patients With Metastatic Melanoma”

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Calcitriol may help temozolomide kill more tumor cells by making them more sensitive to the drug. Calcitriol may also stop the growth of melanoma by blocking blood flow to the tumor.

PURPOSE: This phase I/II trial is studying the best dose of calcitriol, the side effects of calcitriol when given together with temozolomide, and to see how well they work in treating patients with metastatic stage IV melanoma.

Study Type: Interventional

Study Design: Treatment

Study Primary Completion Date: November 2011

OBJECTIVES:

Primary - Determine the maximum tolerate dose of high-dose calcitriol when administered with temozolomide in patients with metastatic melanoma. - Assess toxicity of seven-day on/seven-day off temozolomide in combination with high-dose calcitriol.

Secondary - Determine tumor response and time to progression. - Investigate the relationship between vitamin D-receptor gene polymorphisms and tumor response.

OUTLINE: This is a dose-escalation study of calcitriol followed by a phase II study. - Phase I: Patients receive oral calcitriol on days 1 and 15 and oral temozolomide on days 2-8 and 16-22. Treatment repeats every 28 days for 2 courses in the absence of unacceptable toxicity. Responding patients continue therapy for up to 6 courses in the absence of unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of calcitriol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity. - Phase II: Patients receive temozolomide and calcitriol at the MTD as in phase I.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 28 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: calcitriol
• Drug: temozolomide

Primary Measures

• Safety and tolerability
  • Safety Issue?: Yes

Secondary Measures

• Tumor response
  • Safety Issue?: No
• Time to progression
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant melanoma
• Any primary tumor site
• Stage IV disease
• CNS metastases allowed
• Measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension as ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• Must have had at least 1 prior systemic therapy
• Patients with no prior systemic therapy are eligible provided they are not candidates for high-dose interleukin-2

PATIENT CHARACTERISTICS:

• ECOG performance status 0, 1, or 2
• Creatinine < 2 mg/dL OR creatinine clearance > 50 mL/min
• Calcium < 10.5 mg/dL
• Phosphorus < 4.3 mg/dL
• Bilirubin normal
• Platelet count > 100,000/mm^3
• WBC > 3,500/mm^3
• Life expectancy ≥ 4 months
• No known HIV positivity
• No evidence of active infection requiring antibiotic therapy
• No other malignancy within the past 5 years except surgically resected basal cell or squamous cell skin cancer
• No significant medical disease which, in the opinion of the investigator, may interfere with study completion
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from all toxic effects of prior therapy
• More than 4 weeks since prior and no concurrent radiotherapy, chemotherapy, or immunotherapy
• No prior temozolomide or dacarbazine
• No investigational agent within 4 weeks prior to study entry
• No concurrent magnesium-containing antacids, digitalis, bile-resin binding drugs, or calcium supplements

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Robert H. Lurie Cancer Center

Overall Clinical Trial Officials and Contacts

Timothy M. Kuzel, MD Study Chair Robert H. Lurie Cancer Center  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00301067

Study ID Number: CDR0000456777

ClinicalTrials.gov Identifier: NCT00301067

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database