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

NCT ID: NCT00002854

Last Updated: 2015-08-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1994-12-31
• Study Completion Date: 2015-08-31

Brief 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.

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.

Conditions

Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sequential high dose chemotherapy

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

carboplatin

Intervention Type: DRUG

cisplatin

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

ifosfamide

Intervention Type: DRUG

mesna

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Interventions

filgrastim

Intervention Type: BIOLOGICAL

carboplatin

Intervention Type: DRUG

cisplatin

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

ifosfamide

Intervention Type: DRUG

mesna

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

George Somlo, MD

Role: STUDY_CHAIR

City of Hope Comprehensive Cancer Center

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Countries

United States

Other Identifiers

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-IRB-94098

Identifier Type: -

Identifier Source: secondary_id

NCI-V96-1042

Identifier Type: -

Identifier Source: secondary_id

CDR0000065102

Identifier Type: REGISTRY

Identifier Source: secondary_id

94098

Identifier Type: -

Identifier Source: org_study_id