Phase I/II Study of High-Dose Calcitriol Plus Temodar for Patients With Metastatic Melanoma

NCT ID: NCT00301067

Last Updated: 2019-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-30
• Study Completion Date: 2012-07-09

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.

Conditions

Metastatic Melanoma

Study Design

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

Study Groups

Cohort 1 - Temozolomide and Calcitriol

Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days.

Calcitriol dose of 0.2 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days.

Group Type: EXPERIMENTAL

Calcitriol

Intervention Type: DIETARY_SUPPLEMENT

The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle

Temozolomide

Intervention Type: DRUG

The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle

Cohort 2 - Temozolomide and Calcitriol

Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days.

Calcitriol dose of 0.3 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days.

Group Type: EXPERIMENTAL

Calcitriol

Intervention Type: DIETARY_SUPPLEMENT

The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle

Temozolomide

Intervention Type: DRUG

The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle

Cohort 3 - Temozolomide and Calcitriol

Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days.

Calcitriol dose of 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days.

Group Type: EXPERIMENTAL

Calcitriol

Intervention Type: DIETARY_SUPPLEMENT

The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle

Temozolomide

Intervention Type: DRUG

The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle

Expansion - Temozolomide and Calcitriol

Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days.

Calcitriol dose of 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days.

Group Type: EXPERIMENTAL

Calcitriol

Intervention Type: DIETARY_SUPPLEMENT

The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle

Temozolomide

Intervention Type: DRUG

The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle

Interventions

Calcitriol

The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle

Intervention Type: DIETARY_SUPPLEMENT

Temozolomide

The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle

Intervention Type: DRUG

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

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Timothy M. Kuzel, MD

Role: STUDY_CHAIR

Robert H. Lurie Cancer Center

Locations

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Countries

United States

Other Identifiers

P30CA060553

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NU-05M1

Identifier Type: -

Identifier Source: secondary_id

NU-0310-093

Identifier Type: -

Identifier Source: secondary_id

SPRI-NU-05M1

Identifier Type: -

Identifier Source: secondary_id

NU 05M1

Identifier Type: -

Identifier Source: org_study_id