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

Purpose

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.

Condition	Intervention	Phase
Metastatic Melanoma	Dietary Supplement: calcitriol Drug: temozolomide	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I/II Study of High-Dose Calcitriol in Combination With Temozolomide for Patients With Metastatic Melanoma

Resource links provided by NLM:

MedlinePlus related topics: Melanoma

Drug Information available for: Calcitriol Temozolomide

Genetic and Rare Diseases Information Center resources: Carcinoid Tumor Neuroepithelioma

U.S. FDA Resources

Further study details as provided by Northwestern University:

Primary Outcome Measures:

Maximum tolerated dose of high-dose calcitriol [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]
Determine the maximum tolerate dose of high-dose calcitriol when administered with temozolomide in patients with metastatic melanoma for up to 12 months
Assess toxicity [ Time Frame: Every 2 weeks for up to 12 months ] [ Designated as safety issue: Yes ]
Assess toxicity of seven-day on/seven-day off temozolomide in combination with high-dose calcitriol for every 2 weeks for up to 12 months

Secondary Outcome Measures:

Tumor response and time to progression [ Time Frame: every 8 weeks for up to 12 months ] [ Designated as safety issue: No ]
Determine tumor response and time to progression every 8 weeks for up to 12 months
The relationship between vitamin D-receptor gene polymorphisms and tumor response [ Time Frame: Prestudy and at disease progression or when patient goes off study ] [ Designated as safety issue: No ]
Investigate the relationship between vitamin D-receptor gene polymorphisms and tumor response at prestudy and at disease progression, or when patient goes off study.


Estimated Enrollment:	28
Study Start Date:	May 2005
Estimated Study Completion Date:	May 2016
Estimated Primary Completion Date:	May 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: temozolomide	Dietary Supplement: calcitriol The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Drug: temozolomide The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle

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


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00301067

Locations


United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013

Sponsors and Collaborators

Northwestern University

National Cancer Institute (NCI)

Investigators


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

More Information


Responsible Party:	Northwestern University
ClinicalTrials.gov Identifier:	NCT00301067 History of Changes
Other Study ID Numbers:	NU 05M1 P30CA060553 NU-05M1 NU-0310-093 SPRI-NU-05M1
Study First Received:	March 8, 2006
Last Updated:	September 24, 2015
Health Authority:	United States: Food and Drug Administration

Keywords provided by Northwestern University:


stage IV melanoma recurrent melanoma

Additional relevant MeSH terms:


Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Nerve Tissue Nevi and Melanomas Temozolomide Dacarbazine Calcitriol Antineoplastic Agents, Alkylating	Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Calcium Channel Agonists Membrane Transport Modulators Vasoconstrictor Agents Vitamins Micronutrients Growth Substances Physiological Effects of Drugs Bone Density Conservation Agents

ClinicalTrials.gov processed this record on September 26, 2016