High-Dose Combination Chemotherapy Plus Peripheral Stem Cell Transplantation In Treating Patients With Advanced Cancer

Study Overview

High-Dose Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Advanced Cancer

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.

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.

Cancer

BIOLOGICAL: filgrastim
DRUG: carboplatin
DRUG: cisplatin
DRUG: cyclophosphamide
DRUG: etoposide
DRUG: ifosfamide
DRUG: mesna
DRUG: paclitaxel
PROCEDURE: peripheral blood stem cell transplantation

94098
P30CA033572 (U.S. NIH Grant/Contract)
CHNMC-IRB-94098
NCI-V96-1042
CDR0000065102 (REGISTRY Identifier) (REGISTRY: NCI PDQ)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 1999-11-01	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2015-08-24
First Submitted that Met QC Criteria 2003-01-26	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2015-08-26
First Posted (ESTIMATED) 2003-01-27	Results First Posted N/A	Last Verified 2015-08

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Sequential high dose chemotherapy	BIOLOGICAL: filgrastim DRUG: carboplatin DRUG: cisplatin DRUG: cyclophosphamide DRUG: etoposide DRUG: ifosfamide DRUG: mesna DRUG: paclitaxel PROCEDURE: peripheral blood stem cell transplantation

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Sequential high dose chemotherapy

BIOLOGICAL: filgrastim

DRUG: carboplatin

DRUG: cisplatin

DRUG: cyclophosphamide

DRUG: etoposide

DRUG: ifosfamide

DRUG: mesna

DRUG: paclitaxel

PROCEDURE: peripheral blood stem cell transplantation

Primary Outcome Measures	Measure Description	Time Frame
Feasibility of two cycles of high dose chemotherapy with stem cell reinfusion		30 days from start of course II of treatment
Toxicity of two cycles of high dose chemothearpy and stem cell reinfusion	Toxicity graded according to the NCI Common Toxicity Criteria and amended for subjects undergoing transplantation	30 days from start of course II of treatment
Maximum tolerated dose of two cycles of high dose chemothearpy and stem cell reinfusion		30 days from start of course II of treatment

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

Physiologic 18 to 55

Karnofsky 80%-100%

Absolute neutrophil count greater than 1,500/mm3
Platelet count greater than 120,000/mm3
Hemoglobin greater than 10 g/dL

Bilirubin less than 1.5 mg/dL
AST/ALT less than 3 times normal

Creatinine less than 1.4 mg/dL
Creatinine clearance at least 70 mL/min
No history of hemorrhagic cystitis

Ejection fraction at least 55% by MUGA
No significant cardiac disease

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

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

See Disease Characteristics
At least 4 weeks since prior immunotherapy

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

Not specified

No prior radiotherapy to more than 20% of bone marrow
At least 4 weeks since prior radiotherapy

See Disease Characteristics

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

STUDY_CHAIR: George Somlo, MD, City of Hope Comprehensive Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

Patients

Caregivers

Clinical Trial Record