High-Dose Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Advanced Cancer
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cancer
Intervention: carboplatin (Drug); cisplatin (Drug); cyclophosphamide (Drug); etoposide (Drug); filgrastim (Drug); ifosfamide (Drug); mesna (Drug); paclitaxel (Drug); peripheral blood stem cell transplantation (Procedure)
Phase: Phase 1
Status: Active, not recruiting
Sponsored by: Beckman Research Institute Official(s) and/or principal investigator(s):
George Somlo, MD, Study Chair, Affiliation: Beckman Research Institute
Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
they stop growing or die. Peripheral stem cell transplantation may allow the doctor to give
higher doses of chemotherapy drugs and kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus peripheral
stem cell transplantation in treating patients who have advanced cancer.
Clinical Details
Official title: PHASE I PILOT STUDY OF SEQUENTIAL HIGH DOSE CYCLES OF CISPLATIN, CYCLOPHOSPHAMIDE, ETOPOSIDE AND IFOSFAMIDE, CARBOPLATIN AND TAXOL WITH AUTOLOGOUS STEM CELL SUPPORT
Study design: Treatment
Detailed description:
OBJECTIVES:
- Evaluate the feasibility of administering 2 courses of high dose chemotherapy consisting
of etoposide, cisplatin, and cyclophosphamide followed by ifosfamide, carboplatin, and
paclitaxel (IC-T), each administered with filgrastim (G-CSF) and autologous stem cell
support, to patients with advanced carcinomas.
- Describe the toxicity of these high dose chemotherapy regimens.
- Define the maximum tolerated dose of paclitaxel deliverable in this high dose regimen.
- Describe the pharmacokinetics of escalating doses of paclitaxel given as a 24-hour
continuous infusion.
- Determine the disposition of carboplatin administered in the IC-T regimen.
OUTLINE: At least 4 weeks prior to chemotherapy, patients undergo stem cell collection
following filgrastim (G-CSF) mobilization. Sufficient stem cells to support 2 courses of
chemotherapy are required. Autologous bone marrow is collected as an adjuvant if stem cell
harvest is inadequate.
Patients then receive high dose cisplatin, etoposide, and cyclophosphamide over 10 days,
followed the next day by infusion of one fourth of the allotted stem cells, with the
remaining allotment infused 2 days later. G-CSF is given for granulocyte support.
Beginning no sooner than 14 weeks from the start of the first course of chemotherapy, stable
and responding patients receive high dose paclitaxel, carboplatin, and ifosfamide over 5
days, followed 2 days later with one-fourth of the allotted stem cells, with the remaining
allotment infused the following day. G-CSF is given for granulocyte support. Groups of 3-6
patients are treated with escalating doses of paclitaxel until the maximum tolerated dose for
this regimen is determined.
Patients are followed monthly for 1 year, every 3 months for 1 year, then as needed at the
physician's discretion for at least 5 years.
PROJECTED ACCRUAL: Three to six patients will be entered at each dose of paclitaxel studied.
Eligibility
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
- Histologically confirmed advanced carcinomas of the following types:
- Breast carcinoma that is ineligible for or patient has refused participation in a
higher priority protocol in the following categories:
- Stage II disease with at least 10 involved lymph nodes and no evidence of
disease (NED) following surgery
- Stage III disease rendered surgically NED with or without radiotherapy
- Stage IV disease following partial response (PR) or complete response (CR)
to surgery, chemotherapy, or radiotherapy
- Prior high dose chemotherapy allowed at discretion of investigator
- No chemoresistant disease rendered surgically NED
- Locoregionally recurrent disease within 2 years of breast conservation with
or without chemotherapy
- Stage III/IV ovarian cancer
- PR/CR following debulking surgery and/or chemotherapy
- Ineligible for or refused participation in higher priority protocols
- Primary soft tissue sarcoma with high-grade disease greater than 10 cm or that is
metastatic
- Rendered surgically NED or achieved PR/CR on any chemotherapeutic or
immunotherapeutic regimen
- Ineligible for or refused participation in higher priority protocols
- Malignant melanoma in the following categories:
- Ulcerative primary tumor with any number of completely resected metastatic lymph
nodes
- Stage II disease with more than 4 involved nodes rendered NED
- Stage III disease rendered surgically NED or achieved PR/CR on any
chemotherapeutic or immunotherapeutic regimen
- Osteosarcoma that is ineligible for or refused participation in higher priority
protocols
- Resected primary with less than 50% tumor necrosis on pathologic review
- Metastatic disease rendered surgically NED or PR/CR on any chemotherapeutic,
radiotherapeutic, or immunotherapeutic regimen
- The following diseases rendered surgically NED or that achieved PR/CR on any
chemotherapeutic, radiotherapeutic, or immunotherapeutic regimen also eligible:
- Small cell bone carcinoma
- Metastatic Ewing's sarcoma
- Metastatic gastrointestinal malignancy
- Recurrent Wilms' tumor
- No CNS metastases
- No current histologically confirmed bone marrow metastases
- Prior bone metastases with resolution at time of entry permitted
PATIENT CHARACTERISTICS:
Age:
- Physiologic 18 to 55
Performance status:
- Karnofsky 80%-100%
Hematopoietic:
- Absolute neutrophil count greater than 1,500/mm3
- Platelet count greater than 120,000/mm3
- Hemoglobin greater than 10 g/dL
Hepatic:
- Bilirubin less than 1. 5 mg/dL
- AST/ALT less than 3 times normal
Renal:
- Creatinine less than 1. 4 mg/dL
- Creatinine clearance at least 70 mL/min
- No history of hemorrhagic cystitis
Cardiovascular:
- Ejection fraction at least 55% by MUGA
- No significant cardiac disease
Pulmonary:
- FEV1 greater than 2 L
- pO2 (room air) greater than 70 mm Hg
- pCO2 (room air) less than 42 mm Hg
- DLCO greater than 60% of predicted
Other:
- No potentially disabling psychosocial history
- No organic or functional CNS dysfunction or other medical problem that would present
party at undue risk
- HIV negative
- Hepatitis B surface antigen negative
- No hearing loss greater than 40 decibels
- No contraindication to the following procedures:
- Collection by apheresis of up to 16 x 10 to the 8th mononuclear cells mobilized
by G-CSF
- Collection of autologous bone marrow, if needed
- No second malignancy except:
- Nonmelanomatous skin cancer
- Carcinoma in situ of the cervix
- Not pregnant or nursing
- Adequate contraception required of fertile patients
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- See Disease Characteristics
- At least 4 weeks since prior immunotherapy
Chemotherapy:
- See Disease Characteristics
- No more than 3 prior chemotherapy regimens (excluding adjuvant therapy)
- No more than 200 mg per square meter of prior cisplatin
- No more than 800 mg per square meter of prior carboplatin
- No prior exposure to greater than 1,000 mg per square meter of "24-hour paclitaxel
equivalents" (using a 1: 1. 3 ratio between paclitaxel doses given by 24-hour infusion
and by 3-hour infusion)
- At least 4 weeks since prior chemotherapy
Endocrine therapy:
- Not specified
Radiotherapy:
- No prior radiotherapy to more than 20% of bone marrow
- At least 4 weeks since prior radiotherapy
Surgery:
- See Disease Characteristics
Locations and Contacts
City of Hope Comprehensive Cancer Center, Duarte, California 91010-3000, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: December 1994
Last updated: May 23, 2008
|
