Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Calcitriol Plus Carboplatin in Treating Patients With Advanced Solid Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	NCI	PCI-97-004 PCI-IRB-970532, NCI-G00-1885, NCT00008086

Objectives

1. Determine the maximum tolerated doses of calcitriol and carboplatin, when given in combination, in patients with advanced solid tumors.
2. Determine the toxic effects of this regimen in these patients.
3. Determine the effect of calcitriol on the pharmacokinetics of carboplatin in these patients.
4. Correlate the pharmacokinetics of carboplatin with the myelosuppression following this regimen in these patients.
5. Determine the safety and efficacy of this regimen in patients with malignant glioma.

Entry Criteria

Disease Characteristics:

• Histologically confirmed advanced solid tumor that is not curable by standard therapy, including glioma and other brain tumors



• Brain metastases allowed following definitive radiotherapy

Prior/Concurrent Therapy:

Biologic therapy:

• At least 4 weeks since prior biologic therapy (regional or systemic)

Chemotherapy:

• At least 4 weeks since prior chemotherapy

Endocrine therapy:

• No concurrent glucocorticoids as antiemetics
• Concurrent exogenous glucocorticoids allowed for treatment of gliomas or other brain tumors

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy

Surgery:

• Not specified

Other:

• Dietary calcium intake of no more than 200-250 mg/day beginning 48 hours before each course and continuing for 7 days
• No concurrent dairy products, green leafy vegetables, molasses, baking powder, fortified cereals, and dry peas and beans

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT no greater than 4 times normal

Renal:

• Creatinine no greater than 1.5 mg/dL

  OR

• Creatinine clearance at least 60 mL/min
• Creatinine no greater than 2.0 mg/dL
• Calcium no greater than 10.5 mg/dL

Cardiovascular:

• No unstable angina
• No symptomatic coronary artery disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 forms of barrier contraception AND 1 form of hormonal contraception for at least 1 week before, during, and for at least 2 weeks after study
• No active infection
• No other concurrent serious condition

Expected Enrollment

Approximately 18-50 patients will be accrued for this study.

Outline

This is a dose-escalation study. Patients are stratified according to disease (brain tumor vs other solid tumor) and accrued in parallel. Patients are assigned to one of two treatment groups.

• Group 1: Patients receive carboplatin IV over 20-30 minutes on day 1 and calcitriol subcutaneously (SC) or orally daily on days 2-4 for the first course only. For subsequent courses, patients receive calcitriol SC or orally daily on days 1-3 and carboplatin IV over 20-30 minutes on day 3.



• Group 2: Patients receive calcitriol SC or orally daily on days 1-3 and carboplatin IV over 20-30 minutes on day 3 for the first, third, and subsequent courses. For the second course only, patients receive carboplatin IV over 20-30 minutes on day 1 and calcitriol SC or orally daily on days 2-4.

In both groups, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Sequential dose escalation of calcitriol is followed by sequential dose escalation of carboplatin. Cohorts of 3-6 patients receive escalating doses of calcitriol and then carboplatin until the maximum tolerated dose (MTD) of the combination is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Trial Contact Information

Trial Lead Organizations

UPMC Cancer Centers

Ramesh Ramanathan, MD, Protocol chair		Ph: 412-648-6507

Registry Information
Official Title		A Phase I Trial of Subcutaneous And/Or Oral Calcitriol [(1,25-COH)2D3] and Carboplatin in Advanced Solid Tumors
Trial Start Date		1996-01-23
Registered in ClinicalTrials.gov		NCT00008086
Date Submitted to PDQ		2000-11-14
Information Last Verified		2002-10-01
NCI Grant/Contract Number		CA47904

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