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

NCT00301067 | Completed Phase 1 Results DMC

• 5 other identifiers: NU 05M1P30CA060553NU-05M1NU-0310-093SPRI-NU-05M1
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Melanoma

Keywords

stage IV melanoma; recurrent melanoma

Outcome Measures

Primary Outcomes (2)

• Number and Frequency of Dose Limiting Toxicities (DLTs) With High-dose Calcitriol in Combination With Temozolomide

  Determine number and frequency of dose limiting toxicities (DLT) of high-dose calcitriol when administered with temozolomide in patients with metastatic melanoma for up to 12 cycles of therapy, where 1 cycle equals 28 days. 3 patients per dose cohort will be entered into the trial at doses of 0.2, 0.3, and 0.5 mcg/kg of calcitriol administered orally. If 1 patient experiences dose limiting toxicity (DLT) at any dose, that dose cohort will be expanded to a maximum of 6 patients. If 1 additional patient experiences DLT at that dose stratum, further dose escalation will cease and the dose cohort immediately preceding the dose cohort where the 2 experiences of DLT occurred will be considered the MTD. If no additional patients experience DLT, dose escalation to the next higher dose stratum will take place. DLT is defined as National Cancer Institute Common Toxicity Criteria, version 3.0 grade 3 toxicity determined to be related to calcitriol.

  From start of treatment, up to 12 cycles where 1 cycle equals 28 days

• Number of Patients With Toxicity

  Toxicity will be assessed for each patient on a seven-day on/seven-day off temozolomide in combination with high-dose calcitriol for every 2 weeks for up to 12 cycles where 1 cycle equals 28 days. Toxicity will be assessed during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0) and defined by any toxicity determined to be at least possibly related to either study drug (temozolomide or calcitriol). In general adverse events (AEs) will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE Grade 3 and grade 4 toxicities where relatedness to either study drug could not be ruled out were collected and recorded only.

  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 (2)

• Tumor Response

  At baseline and every 8 weeks during treatment for a maximum of 12 cycles where one cycle equals 28 days.

• The Relationship Between Vitamin D-receptor Gene Polymorphisms and Tumor Response

  Baseline and at disease progression or when patient goes off study up to a maximum of 12 months

Study Arms (4)

Cohort 1 - Temozolomide and Calcitriol

EXPERIMENTAL

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.

Dietary Supplement: Calcitriol; Drug: Temozolomide

Cohort 2 - Temozolomide and Calcitriol

EXPERIMENTAL

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.

Dietary Supplement: Calcitriol; Drug: Temozolomide

Cohort 3 - Temozolomide and Calcitriol

EXPERIMENTAL

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.

Dietary Supplement: Calcitriol; Drug: Temozolomide

Expansion - Temozolomide and Calcitriol

EXPERIMENTAL

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.

Dietary Supplement: Calcitriol; Drug: Temozolomide

Interventions

Calcitriol DIETARY_SUPPLEMENT

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

Cohort 1 - Temozolomide and Calcitriol; Cohort 2 - Temozolomide and Calcitriol; Cohort 3 - Temozolomide and Calcitriol; Expansion - Temozolomide and Calcitriol

Temozolomide 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 1 - Temozolomide and Calcitriol; Cohort 2 - Temozolomide and Calcitriol; Cohort 3 - Temozolomide and Calcitriol; Expansion - Temozolomide and Calcitriol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, 60611-3013, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Calcitriol; Temozolomide

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Dihydroxycholecalciferols; Hydroxycholecalciferols; Cholecalciferol; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Clinical Trials Office
• Organization: Northwestern University

312-695-1301

Study Officials

• Timothy M. Kuzel, MD

  Robert H. Lurie Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 8, 2006
• First Posted: March 10, 2006
• Study Start: January 30, 2005
• Primary Completion: April 5, 2012
• Study Completion: July 9, 2012
• Last Updated: June 4, 2019
• Results First Posted: December 28, 2018

Record last verified: 2019-05

Locations

US (1)