Combination Chemotherapy in Treating Young Patients With Advanced Solid Tumors

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Childhood Central Nervous System Teratoma

Childhood Central Nervous System Mixed Germ Cell Tumor

Childhood Central Nervous System Germ Cell Tumor

Childhood Central Nervous System Embryonal Tumor

Recurrent Childhood Central Nervous System Embryonal Tumor

Childhood Central Nervous System Choriocarcinoma

Childhood Central Nervous System Yolk Sac Tumor

Unspecified Childhood Solid Tumor, Protocol Specific

Recurrent Childhood Brain Stem Glioma

Childhood Central Nervous System Germinoma

Treatments

Procedure: positron emission tomography

Drug: leucovorin calcium

Other: pharmacological study

Drug: fluorouracil

Drug: oxaliplatin

Procedure: computed tomography

Study type

Interventional

Funder types

NIH

Identifiers

NCT00281944

NCI-2009-01051

CDR0000454709

MSKCC-040336

NCI-6952

04-0336

POETIC-COMIRB-040336

Details and patient eligibility

About

This phase I trial is studying the side effects and best dose of oxaliplatin when given together with leucovorin and fluorouracil in treating young patients with advanced solid tumors. Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

Full description

PRIMARY OBJECTIVES:

I. Determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of oxaliplatin when given together with fluorouracil and leucovorin calcium in pediatric patients with recurrent or refractory solid tumors, including tumors of the CNS.

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetic properties of oxaliplatin in this pediatric patient population.

II. Correlate alterations in accumulation of fludeoxyglucose F 18 with tumor response in those patients who can readily undergo a positron emission tomography (PET) or PET/CT scan.

III. Assess the safety profile of this regimen in these patients. IV. Evaluate any preliminary evidence of anti-tumor activity of this regimen in these patients.

OUTLINE: This is an open-label, multicenter, dose-escalation study of oxaliplatin. Patients are stratified according to solid tumor type (non-CNS vs CNS).

Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 followed by fluorouracil IV continuously over 46 hours on days 1-2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

After completion of study treatment, patients are followed periodically.

Enrollment

42 patients

Sex

All

Ages

Under 21 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Histologically diagnosed malignant solid tumor, including tumors of the CNS, that has progressed despite standard therapy or for which no effective standard therapy is known
- Patients with brainstem glioma or intrinsic pontine glioma do not need biopsy proof of the diagnosis if imaging studies are consistent with the diagnosis
Measurable or nonmeasurable disease
No pleural effusion or ascites causing respiratory compromise (≥ grade 2 dyspnea)
ECOG performance status (PS) 0-2 for patients ≥ 16 years of age
Karnofsky PS ≥ 40% for patients > 10 years of age
Lansky Play Scale ≥ 40% for patients ≤ 10 years of age
Peripheral absolute neutrophil count (ANC) ≥ 1,000/mm^3
Platelet count ≥ 75,000/mm^3 (transfusion independent)
Hemoglobin ≥ 8.5 g/dL (transfusion permitted)
Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
Creatinine clearance OR radioisotope glomerular filtration rate > 60mL/min
Total bilirubin < 1.5 mg/dL
ALT and AST ≤ 2.5 times ULN (5 times ULN if liver involvement with primary tumor)
Ejection fraction ≥ 50% OR shortening fraction ≥ 28%
Life expectancy of > 8 weeks
No radiological evidence of pulmonary fibrosis, interstitial pneumonia, or extensive and symptomatic interstitial fibrosis of the lung
- Room air oxygen saturation ≥ 90% at altitudes ≥ 5,000 feet OR ≥ 93% at altitudes < 5,000 feet
- DLCO > 50% of predicted (for patients who received prior bleomycin and are able to comply with pulmonary function testing)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to platinum or oxaliplatin as well as other agents used in study treatment
No other serious or poorly controlled social circumstance, psychiatric illness, or medical condition including, but not limited to, the following: ongoing or active infection, uncontrolled seizure disorder, uncontrolled symptomatic congestive heart failure, or cardiac arrhythmia that could be exacerbated by or complicate compliance with study therapy
No HIV-positive patients
Recovered from prior therapy
- No persistent toxicities from previous therapies ≥ grade 2
  - Stable grade 3 neurotoxicity is allowed in patients with CNS tumors only who have a baseline neurotoxicity due to primary tumor involvement or postoperative complications
At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
At least 4 weeks since prior local radiotherapy (small port)
At least 6 months since prior craniospinal irradiation, irradiation to ≥ 50% of the pelvis, or other substantial bone marrow irradiation, including total body irradiation
No previous treatment with oxaliplatin
At least 14 days since prior biological therapy (including monoclonalantibody therapy)
At least 7 days since prior retinoids, sargramostim (GM-CSF), or filgrastim (G-CSF)
At least 14 days since prior pegfilgrastim
No concurrent pegfilgrastim or GM-CSF
Patients requiring steroids should be on stable or decreasing dose for ≥ 7 days prior to study entry, and must not be on more than 4 mg of dexamethasone (or equivalent) per day
At least 4 weeks since prior major surgical procedure
- Simple surgical procedures, including biopsy or central line placement or similar procedure, are allowed within 4 weeks of study entry if the patient has recovered to baseline
At least 3 months since prior autologous or allogeneic stem cell transplantation
- No concurrent immunosuppressive therapy
- No evidence of ongoing graft versus host disease (GVHD)
No concurrent use of other investigational agents
No other concurrent anticancer therapies or agents
No other concurrent chemotherapy, radiation therapy, or herbal medications or supplements