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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00002854
First received: November 1, 1999
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Cancer
Biological: filgrastim
Drug: carboplatin
Drug: cisplatin
Drug: cyclophosphamide
Drug: etoposide
Drug: ifosfamide
Drug: mesna
Drug: paclitaxel
Procedure: peripheral blood stem cell transplantation
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Estimated Enrollment: 6
Study Start Date: December 1994
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002854

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Study Chair: George Somlo, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00002854     History of Changes
Other Study ID Numbers: 94098, P30CA033572, CHNMC-IRB-94098, NCI-V96-1042, CDR0000065102
Study First Received: November 1, 1999
Last Updated: December 16, 2013
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
stage IV colon cancer
stage II breast cancer
stage IV breast cancer
stage IIIA breast cancer
recurrent breast cancer
stage IV gastric cancer
recurrent gastric cancer
localized osteosarcoma
metastatic osteosarcoma
stage IIIB breast cancer
recurrent pancreatic cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
stage IV anal cancer
recurrent anal cancer
stage IV esophageal cancer
recurrent esophageal cancer
stage III adult soft tissue sarcoma
recurrent adult soft tissue sarcoma
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian epithelial cancer
recurrent Wilms tumor and other childhood kidney tumors
advanced adult primary liver cancer
recurrent adult primary liver cancer
recurrent osteosarcoma
recurrent gallbladder cancer
recurrent extrahepatic bile duct cancer
recurrent small intestine cancer

Additional relevant MeSH terms:
Carboplatin
Cisplatin
Cyclophosphamide
Etoposide
Ifosfamide
Isophosphamide mustard
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 29, 2014