Combination Chemotherapy in Treating Young Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00281944
First received: January 24, 2006
Last updated: May 1, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Childhood Central Nervous System Choriocarcinoma
Childhood Central Nervous System Embryonal Tumor
Childhood Central Nervous System Germ Cell Tumor
Childhood Central Nervous System Germinoma
Childhood Central Nervous System Mixed Germ Cell Tumor
Childhood Central Nervous System Teratoma
Childhood Central Nervous System Yolk Sac Tumor
Recurrent Childhood Brain Stem Glioma
Recurrent Childhood Central Nervous System Embryonal Tumor
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: oxaliplatin
Drug: fluorouracil
Drug: leucovorin calcium
Other: pharmacological study
Procedure: positron emission tomography
Procedure: computed tomography
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-Center Phase Ib Study of Oxaliplatin (NSC #266046) in Combination With Fluorouracil and Leucovorin in Pediatric Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD based on the incidence of DLT as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 3.0 [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  • DLT defined as any grade 3 or greater non-hematologic toxicity attributed to the combination of drugs in this regimen, despite maximal supportive care as assessed by NCI CTCAE v. 3 [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    .


Secondary Outcome Measures:
  • Safety profile as assessed by NCI CTCAE v. 3.0 [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    Any incidence of adverse events will be recorded and classified according to body region and severity.

  • Tumor response based on PET or PET/CT scan [ Time Frame: From baseline to 6 weeks ] [ Designated as safety issue: No ]
    Wilcoxon rank sum statistic will be used to assess whether tumor response is associated with the change in the PET SUV value.


Enrollment: 42
Study Start Date: September 2005
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (oxaliplatin, leucovorin calcium, fluorouracil)
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.
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Procedure: positron emission tomography
Undergo PET scan
Other Names:
  • FDG-PET
  • PET
  • PET scan
  • tomography, emission computed
Procedure: computed tomography
Undergo PET/CT scan
Other Name: tomography, computed

Detailed 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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00281944

Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Investigators
Principal Investigator: Lia Gore Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00281944     History of Changes
Other Study ID Numbers: NCI-2009-01051, 04-0336, MSKCC-040336, CDR0000454709, NCI-6952, POETIC-COMIRB-040336
Study First Received: January 24, 2006
Last Updated: May 1, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Neoplasms, Germ Cell and Embryonal
Endodermal Sinus Tumor
Choriocarcinoma
Neoplasms by Histologic Type
Mesonephroma
Trophoblastic Neoplasms
Gestational Trophoblastic Disease
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Pregnancy Complications, Neoplastic
Pregnancy Complications
Oxaliplatin
Fluorouracil
Levoleucovorin
Leucovorin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes
Protective Agents
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on September 18, 2014