Clinical trial NCT00301067: Phase I/II Study of High-Dose Calcitriol Plus Temodar for Patients With Metastatic Melanoma
Official title: A Phase I/II Study of High-Dose Calcitriol in Combination With Temozolomide for Patients With Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Melanoma
Keywords: stage IV melanoma
recurrent melanoma
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-03-10
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 3+3 dose escalation design study. (3) patients per dose stratum will be entered in the following cohorts:

Cohort 1 - Temozolomide and Calcitriol 0.2mcg/kg days 1 + 15

Cohort 2 - Temozolomide and Calcitriol 0.3 mcg/kg days 1 + 15

Cohort 3 - Temozolomide and Calcitriol 0.5 mcg/kg days 1 + 15

Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every 28 day cycle in each cohort.

If 1 patient experiences dose limiting toxicity (DLT) at any dose, that cohort will be expanded to 6 patients. If 2 patients experience DLT in that cohort, further dose escalation will cease and the cohort immediately preceding that cohort will be considered the maximum tolerated dose (MTD). Alternatively, if no more patients experience DLT, then dose will be escalated to the next cohort.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: \* 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.

Eligibility criteria: Inclusion Criteria:

* 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
* Negative pregnancy test
* Fertile patients must use effective contraception

  * Patients with no prior systemic therapy are eligible provided they are not candidates for high-dose interleukin-2
* Recovered from all toxic effects of prior therapy
* More than 4 weeks since prior and no concurrent radiotherapy, chemotherapy, or immunotherapy
* More than 4 weeks since prior and no concurrent radiotherapy, chemotherapy, or immunotherapy
* Fertile patients must use effective contraception

Exclusion Criteria:

* Life expectancy less than 4 months
* known HIV positivity
* evidence of active infection requiring antibiotic therapy
* other malignancy within the past 5 years except surgically resected basal cell or squamous cell skin cancer
* significant medical disease which, in the opinion of the investigator, may interfere with study completion
* pregnant or nursing
* Negative pregnancy test
* prior temozolomide or dacarbazine
* investigational agent within 4 weeks prior to study entry
* concurrent magnesium-containing antacids, digitalis, bile-resin binding drugs, or calcium supplements

Primary outcomes:
measure: Number and Frequency of Dose Limiting Toxicities (DLTs) With High-dose Calcitriol in Combination With Temozolomide
timeFrame: From start of treatment, up to 12 cycles where 1 cycle equals 28 days
measure: Number of Patients With Toxicity
timeFrame: From the start of treatment and every 2 weeks for a maximum of 12 cycles, and 30 days post last treatment, where 1 cycle equals 28 days
Secondary outcomes:
measure: Tumor Response
timeFrame: At baseline and every 8 weeks during treatment for a maximum of 12 cycles where one cycle equals 28 days.
measure: The Relationship Between Vitamin D-receptor Gene Polymorphisms and Tumor Response
timeFrame: Baseline and at disease progression or when patient goes off study up to a maximum of 12 months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
Study officials:
affiliation: Robert H. Lurie Cancer Center
name: Timothy M. Kuzel, MD
role: STUDY_CHAIR
References: