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

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Metastatic Melanoma	Dietary Supplement: calcitriol; Drug: temozolomide	Phase 1; Phase 2

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.

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	28 participants
Intervention Model:	Single Group Assignment
Masking:	None (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
Study Start Date :	May 2005
Estimated Primary Completion Date :	May 2018
Estimated Study Completion Date :	May 2019

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
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

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Maximum tolerated dose of high-dose calcitriol [ Time Frame: Up to 12 months ]
   Determine the maximum tolerate dose of high-dose calcitriol when administered with temozolomide in patients with metastatic melanoma for up to 12 months
2. Assess toxicity [ Time Frame: Every 2 weeks for up to 12 months ]
   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 :

1. Tumor response and time to progression [ Time Frame: every 8 weeks for up to 12 months ]
   Determine tumor response and time to progression every 8 weeks for up to 12 months
2. The relationship between vitamin D-receptor gene polymorphisms and tumor response [ Time Frame: Prestudy and at disease progression or when patient goes off study ]
   Investigate the relationship between vitamin D-receptor gene polymorphisms and tumor response at prestudy and at disease progression, or when patient goes off study.

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Northwestern University
ClinicalTrials.gov Identifier:	NCT00301067 History of Changes
Other Study ID Numbers:	NU 05M1; P30CA060553 ( U.S. NIH Grant/Contract ); NU-05M1; NU-0310-093; SPRI-NU-05M1
First Posted:	March 10, 2006
Last Update Posted:	December 21, 2017
Last Verified:	December 2017

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