Know Cancer

or
forgot password

A Multi-Center Phase Ib Study of Oxaliplatin (NSC #266046) in Combination With Fluorouracil and Leucovorin in Pediatric Patients With Advanced Solid Tumors


Phase 1
N/A
21 Years
Not Enrolling
Both
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

Thank you

Trial Information

A Multi-Center Phase Ib Study of Oxaliplatin (NSC #266046) in Combination With Fluorouracil and Leucovorin in Pediatric Patients With Advanced Solid Tumors


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

14 days

Safety Issue:

Yes

Principal Investigator

Lia Gore

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-01051

NCT ID:

NCT00281944

Start Date:

September 2005

Completion Date:

Related Keywords:

  • 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
  • Choriocarcinoma
  • Endodermal Sinus Tumor
  • Glioma
  • Carcinoma, Embryonal
  • Neoplasms, Germ Cell and Embryonal
  • Teratoma
  • Germinoma
  • Neoplasms

Name

Location

Memorial Sloan Kettering Cancer CenterNew York, New York  10021