Clinical trial NCT00008086: Calcitriol Plus Carboplatin in Treating Patients With Advanced Solid Tumors
Official title: A Phase I Trial of Subcutaneous And/Or Oral Calcitriol [(1,25-COH)2D3] and Carboplatin in Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: recurrent adult brain tumor
adult brain stem glioma
adult craniopharyngioma
adult medulloblastoma
adult meningioma
adult glioblastoma
unspecified adult solid tumor, protocol specific
adult anaplastic astrocytoma
adult myxopapillary ependymoma
adult anaplastic ependymoma
adult anaplastic oligodendroglioma
adult mixed glioma
adult central nervous system germ cell tumor
adult pilocytic astrocytoma
adult subependymoma
adult ependymoblastoma
adult pineocytoma
adult pineoblastoma
adult meningeal hemangiopericytoma
adult choroid plexus tumor
adult grade III meningioma
adult oligodendroglioma
adult giant cell glioblastoma
adult gliosarcoma
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-09-04
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Calcitriol may help solid tumor cells develop into normal cells. Combining calcitriol with chemotherapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of calcitriol combined with carboplatin in treating patients who have advanced solid tumors.

Detailed description: OBJECTIVES:

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

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.

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

Eligibility 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

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/mm\^3
* Platelet count at least 100,000/mm\^3

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

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Ramesh K. Ramanathan, MD
role: STUDY_CHAIR
References: