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

August 24, 2015 updated by: City of Hope Medical Center

PHASE I PILOT STUDY OF SEQUENTIAL HIGH DOSE CYCLES OF CISPLATIN, CYCLOPHOSPHAMIDE, ETOPOSIDE AND IFOSFAMIDE, CARBOPLATIN AND TAXOL WITH AUTOLOGOUS STEM CELL SUPPORT

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
33

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010-3000
        • City of Hope Comprehensive Cancer Center

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.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Sequential high dose chemotherapy
Drug: carboplatin
Drug: cyclophosphamide
Drug: etoposide
Drug: cisplatin
Procedure: peripheral blood stem cell transplantation
Drug: paclitaxel
Biological: filgrastim
Drug: ifosfamide
Drug: mesna

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Feasibility of two cycles of high dose chemotherapy with stem cell reinfusion
Time Frame: 30 days from start of course II of treatment
30 days from start of course II of treatment
Toxicity of two cycles of high dose chemothearpy and stem cell reinfusion
Time Frame: 30 days from start of course II of treatment
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
Time Frame: 30 days from start of course II of treatment
30 days from start of course II of treatment

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
City of Hope Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: George Somlo, MD, City of Hope Comprehensive Cancer Center

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 Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 1994

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 1, 1999

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 26, 2003

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 26, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 24, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 94098
  • P30CA033572 (U.S. NIH Grant/Contract)
  • CHNMC-IRB-94098
  • NCI-V96-1042
  • CDR0000065102 (Registry Identifier: NCI PDQ)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings