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A Trial of Irinotecan and Cisplatin in Children With Refractory Solid Tumors

Phase 1
1 Year
21 Years
Open (Enrolling)
Unspecified Childhood Solid Tumor, Protocol Specific

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Trial Information

A Trial of Irinotecan and Cisplatin in Children With Refractory Solid Tumors


I. Determine the maximum tolerated dose (MTD) of irinotecan when administered with
cisplatin, with or without amifostine, to children with refractory solid tumors.

II. Determine the dose limiting toxicities of the combination of irinotecan and cisplatin,
with and without amifostine, in this patient population.

III. Determine the pharmacokinetics of cisplatin with and without amifostine in these

IV. Quantify the leukocyte DNA-platinum adduct formation, with and without amifostine, and
correlate it with response and toxicity in these patients.

V. Determine the safety and efficacy of the doses and schedules of administration to be used
in phase II clinical trials.

OUTLINE: This is a dose escalation study of irinotecan.

Treatment A: Patients receive cisplatin IV over 1 hour followed immediately by irinotecan IV
over 90 minutes on days 1, 8, 15, and 22. Courses repeat every 6 weeks. Treatment continues
for a minimum of 2 courses in the absence of unacceptable toxicity or disease progression.

Treatment B: Patients receive therapy as in treatment A. In addition, amifostine IV is
administered over 15 minutes immediately before cisplatin.

Cohorts of 3-6 patients receive escalating doses of irinotecan 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 toxicities. Once the MTD of treatment A is
determined, additional patients are accrued to determine the MTD of treatment B.

If myelosuppression is the dose limiting toxicity of treatment A, then stratum 1 closes and
stratum 2 opens and these patients with less prior therapy receive treatment A. Treatment B
is then only open to stratum 3 patients.

Patients are followed every 6 months for 4 years, then annually thereafter.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study within 2.5 years.

Inclusion Criteria:


- Each patient must have a proven pathologic diagnosis of solid tumor; the tumor must
be refractory to conventional therapies, or for which no effective therapy is known;
patients with brain tumors are eligible, but they should not be receiving
anticonvulsants; the requirement for histologic diagnosis can be waived for patients
with brainstem gliomas

- Karnofsky >= 50% for patients > 10 years of age; Lansky play scale >= 50% for
children =< 10 years of age; neurologic deficits in patients with CNS tumors must
have been relatively stable for a minimum of 2 weeks prior to study entry; patients
who are unable to walk because of paralysis, but who are up in a wheelchair will be
considered ambulatory for the purpose of assessing the performance score

- Life expectancy >= 8 weeks

- Nutrition status >= 3rd percentile weight for height and serum albumin >= 2.5 g%

- Prior therapy: patients must have recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study, and must
be without significant systemic illness (e.g., infection, fever, mucositis, severe
anorexia, and severe malnutrition)

- Myelosuppressive chemotherapy must not have been received within 3 weeks of
entry on this study (six weeks if a prior nitrosourea)

- Biologic, anti-neoplastic agents must not have received at least 1 week

- Radiation >= 2 weeks must have been elapsed from prior local radiation (small
port); >= 6 months must have been elapsed from prior craniospinal radiation or
>= 50% radiation of the pelvis; 6 weeks must have been elapsed from substantial
bone marrow radiation

- Autologous or allogeneic BMT without TBI >= 6 months must have been elapsed,
with no evidence of GVH disease

- Growth factor(s) must not have been received within one week of entry on this study

- Steroids: patients with CNS tumors who are receiving dexamethasone must be on a
stable or decreasing dose for at least 2 weeks prior to study entry

- ANC >= 1,000/ul

- Hemoglobin >= 8.0 g/dL

- Platelet count >= 100,000/ul

- Bilirubin =< 1.5 mg/dL

- SGPT =< 2 times upper limit of normal

- Albumin >= 2.5 g/dL

- Normal serum creatinine for age or, if abnormal serum creatinine, normal GFR for age

- All patients (or their legal guardians if patient is less than 18 years of age) must
sign a document of informed consent that has been approved by the Institutional Human
Review Committee; when appropriate the patient will be included in all discussions in
order to obtain verbal assent

- The Phase I Office must give permission to register the patient; registration must
occur on the day the patient receives the treatment; however, the registration should
precede the drug administration

- Protocol must be approved by the local Institutional Review Board (IRB) prior to any
patient registration and reapproved every twelve months

Exclusion Criteria:


- Pregnant or breast-feeding women will not be entered on this study; pregnancy tests
must be obtained in girls who are post-menarchal; males or females of reproductive
potential may not participate unless they have agreed to use an effective
contraceptive method

- Patients who have uncontrolled infections are not eligible for this study

- Patients who are receiving any other chemotherapy or investigational agents are not
eligible for this study

- Patients who are receiving anticonvulsants are not eligible for this study


- Patients who have received more than two prior chemotherapy regimens (single or
multi-agent regimens)

- Patients who have had central axis radiation

- Patients with bone marrow involvement

- Patients who have had prior stem cell transplantation (with or without TBI)

Type of Study:


Study Design:

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

Outcome Measure:

MTD defined as that dose level immediately below the dose level at which 2 patients out of 3 to 6 patients experienced dose-limiting toxicity using Common Toxicity Criteria version 2.0

Outcome Time Frame:

6 weeks

Safety Issue:


Principal Investigator

Abdul Kader Souid

Investigator Role:

Principal Investigator

Investigator Affiliation:

Swiss Pediatric Oncology Group - Geneva


United States: Food and Drug Administration

Study ID:




Start Date:

December 1999

Completion Date:

Related Keywords:

  • Unspecified Childhood Solid Tumor, Protocol Specific
  • Neoplasms