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

This study is ongoing, but not recruiting participants.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Northwestern University Identifier:
First received: March 8, 2006
Last updated: September 24, 2015
Last verified: September 2015

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:

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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 identifier: NCT00301067

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

Responsible Party: Northwestern University 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:
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Bone Density Conservation Agents
Calcium Channel Agonists
Growth Substances
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Vasoconstrictor Agents
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