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A Phase I Trial of Subcutaneous And/Or Oral Calcitriol [(1,25-COH)2D3] and Carboplatin in Advanced Solid Tumors


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Brain and Central Nervous System Tumors, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Trial of Subcutaneous And/Or Oral Calcitriol [(1,25-COH)2D3] and Carboplatin in Advanced Solid Tumors


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Ramesh K. Ramanathan, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Pittsburgh

Authority:

United States: Federal Government

Study ID:

CDR0000068374

NCT ID:

NCT00008086

Start Date:

January 1996

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • Unspecified Adult Solid Tumor, Protocol Specific
  • 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
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms
  • Neoplasms

Name

Location

University of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania  15213