Clinical trial NCT00012181: Flavopiridol in Treating Children With Relapsed or Refractory Solid Tumors or Lymphomas
Official title: A PHASE I STUDY OF FLAVOPIRIDOL (NSC# 649890; IND# 46211) IN PATIENTS WITH RELAPSED OR REFRACTORY PEDIATRIC SOLID TUMORS OR LYMPHOMAS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Recurrent Childhood Brain Stem Glioma
Recurrent Childhood Cerebellar Astrocytoma
Recurrent Childhood Cerebral Astrocytoma
Recurrent Childhood Ependymoma
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Liver Cancer
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Malignant Germ Cell Tumor
Recurrent Childhood Medulloblastoma
Recurrent Childhood Rhabdomyosarcoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Recurrent Childhood Soft Tissue Sarcoma
Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor
Recurrent Childhood Visual Pathway and Hypothalamic Glioma
Recurrent Childhood Visual Pathway Glioma
Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
Recurrent Neuroblastoma
Recurrent Osteosarcoma
Recurrent Retinoblastoma
Recurrent Wilms Tumor and Other Childhood Kidney Tumors
Recurrent/Refractory Childhood Hodgkin Lymphoma
Unspecified Childhood Solid Tumor, Protocol Specific
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 30
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Phase I trial to study the effectiveness of flavopiridol in treating children who have relapsed or refractory solid tumors or lymphoma.

Detailed description: PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of flavopiridol in children with relapsed or refractory solid tumors or lymphomas.

II. Determine the toxic effects and pharmacokinetics of this drug in these patients.

III. Determine the antitumor activity of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive flavopiridol IV over 1 hour on days 1-3. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3 to 6 patients receive escalating doses of flavopiridol 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.

Patients are followed every 6 months.

PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 18 months.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed relapsed or refractory solid tumor or lymphoma including:

  * Neuroblastoma
  * Osteosarcoma
  * Ewing's sarcoma
  * Rhabdomyosarcoma
  * Wilms tumor
  * CNS tumors
* Histological verification not required for brainstem tumors
* No acute leukemia
* Not eligible for higher priority COG phase I/II study
* Performance status - Karnofsky 50-100% (over age 10)
* Performance status - Lansky 50-100% (age 10 and under)
* At least 2 months
* Absolute neutrophil count at least 1,000/mm\^3
* Platelet count at least 75,000/mm\^3 (transfusion independent)
* Hemoglobin at least 8.0 g/dL (transfusion allowed)
* No granulocytopenia, anemia, and/or thrombocytopenia due to bone marrow involvement
* Bilirubin no greater than 1.5 times normal
* SGPT no greater than 5 times normal
* Albumin at least 2 g/dL
* Creatinine no greater than 1.5 times normal
* Creatinine clearance or radioisotope glomerular filtration rate at least lower limit of normal
* Shortening fraction at least 27% by echocardiogram
* Ejection fraction at least 50% by MUGA
* Stable neurologic deficits within the past 2 weeks for patients with CNS tumors
* CNS toxicity less than grade 2
* No active graft-versus-host disease
* No active uncontrolled infection or other serious medical condition
* No uncontrolled diabetes mellitus
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* At least 7 days since prior biologic therapy and recovered
* Prior bone marrow or stem cell transplantation allowed
* At least 6 months since prior allogeneic stem cell transplantation
* At least 1 week since prior growth factors
* No concurrent immunomodulating agents
* At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
* No other concurrent chemotherapy
* Concurrent dexamethasone for CNS tumors allowed if on stable dose for at least 2 weeks prior to study
* Concurrent corticosteroids allowed only for increased intracranial pressure in patients with CNS tumors
* At least 2 weeks since prior local (small port) palliative radiotherapy
* At least 6 months since prior radiotherapy to 50% or more of the pelvis
* At least 6 months since prior craniospinal radiotherapy
* At least 6 weeks since other prior substantial bone marrow radiotherapy
* Recovered from prior radiotherapy
* No concurrent radiotherapy except localized palliative radiotherapy
* No concurrent anticonvulsants

Primary outcomes:
measure: MTD defined as the dose at which fewer than one-third of patients experience DLT assessed using Common Toxicity Criteria version 2.0
timeFrame: Day 21
Secondary outcomes:
Other outcomes:
Locations:
city: Arcadia
country: United States
facility: COG Phase I Consortium
state: California
Study officials:
affiliation: COG Phase I Consortium
name: James Whitlock
role: PRINCIPAL_INVESTIGATOR
References: