Clinical trial NCT00004189: Rebeccamycin Analog and Cisplatin With or Without Filgrastim in Treating Patients With Advanced Cancer
Official title: A Phase I and Pharmacokinetic Study of Sequences of NSC 655649 (Rebeccamycin Analogue) and Cisplatin Without and With Granulocyte Colony-Stimulating Factor Support Every 21 Days
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
recurrent adult Hodgkin lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
small intestine lymphoma
unspecified adult solid tumor, protocol specific
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult Burkitt lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
recurrent adult T-cell leukemia/lymphoma
primary central nervous system non-Hodgkin lymphoma
AIDS-related peripheral/systemic lymphoma
AIDS-related primary CNS lymphoma
intraocular lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
recurrent mycosis fungoides/Sezary syndrome
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage III marginal zone lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase I trial to study the effectiveness of rebeccamycin analog and cisplatin with or without filgrastim in treating patients who have advanced cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.

Detailed description: OBJECTIVES:

I. Determine the maximum tolerated doses of a rebeccamycin analogue and cisplatin with or without filgrastim (G-CSF) in patients with advanced malignancies.

II. Determine the qualitative and quantitative toxicities of these regimens in these patients.

III. Determine if the pharmacokinetics of a rebeccamycin analogue are affected by cisplatin and if there are sequence dependent pharmacokinetic effects.

IV. Assess any antitumor effects of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study of a rebeccamycin analogue and cisplatin.

Part I (previously untreated or minimally pretreated patients): The first patient of each cohort receives cisplatin IV over 1 hour followed 2 hours later by a rebeccamycin analogue IV over 1 hour on day 1. The second patient in the same cohort receives the same drugs in the reverse order. The drug sequence for each additional patient within the same cohort is alternated with reference to the preceding patient. During each subsequent course, the study drugs are administered to each patient in the reverse order as compared to the prior course. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Dose escalation is initially performed without filgrastim (G-CSF). Cohorts of 4-6 patients receive escalating doses of a rebeccamycin analogue and cisplatin until the maximum tolerated dose (MTD) of each drug is determined. The MTD is defined as the highest dose at which less than 2 of 6 patients experience dose limiting toxicity (DLT). If 2 of the first 6 patients experience DLT, then dose escalation proceeds in combination with G-CSF treatment. Patients receive G-CSF subcutaneously daily beginning on day 2 and continuing until blood counts have recovered for 2 days or until approximately day 15. Cohorts of 4-6 patients receive escalating doses of a rebeccamycin analogue and cisplatin as above. The MTD is defined as above.

Part II (heavily pretreated patients): Heavily pretreated patients receive a rebeccamycin analogue and cisplatin starting at 2 dose levels preceding the MTD from part I.

Patients are followed for at least 30 days.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically proven advanced malignancy that is refractory to prior therapy or unlikely to benefit from standard therapy (e.g., chemotherapy, radiotherapy, and surgery)

  * Part I: Previously untreated OR minimally pretreated

    * Ineligible for part I and considered heavily pretreated if:

      * Prior radiotherapy to wide ports involving the pelvis or at least 25% of bone marrow
      * Greater than 6 courses of prior combination chemotherapy including alkylating agent
      * Prior nitrosoureas or mitomycin
      * Widespread bone metastases with bone marrow involvement by bone marrow biopsy (positive bilateral bone marrow biopsy for lymphoma patients)
  * Part II: Heavily pretreated as defined above
* Measurable or evaluable disease

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* SWOG 0-2

Life expectancy:

* At least 3 months

Hematopoietic:

* Absolute neutrophil count greater than 1,500/mm\^3
* Hemoglobin greater than 9 mg/dL
* Platelet count greater than 100,000/mm\^3

Hepatic:

* Bilirubin less than 1.5 mg/dL

Renal:

* Creatinine less than 1.5 mg/dL

Cardiovascular:

* No uncontrolled hypertension
* No angina pectoris
* No clinically significant, multifocal, uncontrolled cardiac dysrhythmias

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No active serious infection
* No clinically severe peripheral neuropathy (grade 1 or worse)
* No nonmalignant medical condition that would preclude compliance or increase risk of participation in study
* No hypersensitivity to E. coli derived drug preparations

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No other concurrent colony stimulating factors for prophylactic purposes

Chemotherapy:

* At least 3 weeks since prior chemotherapy (6 weeks since prior nitrosoureas and mitomycin) and recovered

Endocrine therapy:

* No chronic oral corticosteroids
* No concurrent corticosteroids except as prophylactic antiemetic

Radiotherapy:

* At least 3 weeks since prior radiotherapy and recovered

Other:

* At least 1 month since prior investigational agent
* No prophylactic oral or IV antibiotics for neutropenia unless fever present
* No other concurrent anticancer treatment or investigational agent

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy and Research Center
state: Texas
city: San Antonio
country: United States
facility: St. Luke's Lutheran Hospital
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center at San Antonio
name: Lisa Hammond, MD
role: STUDY_CHAIR
References: