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

Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002854
• Other study ID #: 94098
• Secondary ID: P30CA033572CHNMC
• Status: Completed
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: August 24, 2015
• Start date: December 1994
• Est. completion date: August 2015

Study information

• Verified date: August 2015
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer

Intervention

Biological:
• filgrastim

Drug:
• carboplatin

• cisplatin

• cyclophosphamide

• etoposide

• ifosfamide

• mesna

• paclitaxel

Procedure:
• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
United States	City of Hope Comprehensive Cancer Center	Duarte	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility of two cycles of high dose chemotherapy with stem cell reinfusion		30 days from start of course II of treatment	Yes
Primary	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	Yes
Primary	Maximum tolerated dose of two cycles of high dose chemothearpy and stem cell reinfusion		30 days from start of course II of treatment	Yes