Amrubicin + Cyclophosphamide in Advanced Solid Organ Malignancies

December 21, 2015 updated by: Lawrence Einhorn

A Phase I Study of Amrubicin and Cyclophosphamide in Patients With Advanced Solid Organ Malignancies

Amrubicin has shown single-agent activity in lung cancer. The combination of cyclophosphamide and anthracyclines has been studied and concluded that the combination was tolerable, could be given safely, and therapeutically useful.

This Phase I study will evaluate the combination of cyclophosphamide with amrubicin in relapsed solid tumors and will define the MTD of the combination in a US population.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OUTLINE: This is a multi-center study.

This study will follow the 3+3 design with the following dose levels:

  • Dose Level -1: Amrubicin 20mg/m2, Cyclophosphamide 500mg/m2
  • Dose Level 1: Amrubicin 25mg/m2, Cyclophosphamide 500mg/m2
  • Dose Level 2: Amrubicin 30mg/m2, Cyclophosphamide 500mg/m2
  • Dose Level 3: Amrubicin 35mg/m2, Cyclophosphamide 500mg/m2
  • Dose Level 4: Amrubicin 40mg/m2, Cyclophosphamide 500mg/m2

Dose escalation starts from dose level 1.

Amrubicin will be given as a slow IV push or infusion over approximately 5 minutes once daily for 3 consecutive days starting on day 1 of each 21 day cycle.

Cyclophosphamide will be given at a fixed dose as an IV infusion over 30-60 minutes on day 1 of each 21 day cycle (following amrubicin).

ECOG Performance Status: 0-1

Life expectancy: not specified

Hematopoietic:

  • Hemoglobin (Hgb) > 9 g/dL.
  • Platelets > 100 K/mm3
  • Absolute Neutrophil Count (ANC) > 1.5 K/mm3

Hepatic:

  • Aspartate transaminase (AST) ≤ 2.5 x ULN
  • Alanine transaminase (ALT) ≤ 2.5 x ULN
  • Total bilirubin < 1.5 x ULN

Renal:

  • Calculated creatinine clearance ≥ 60cc/min

Cardiovascular:

  • Left Ventricular Ejection Fraction (LVEF) ≥ LLN for institution within 60 days prior to registration for protocol therapy.
  • No history of cardiomyopathy or uncontrolled heart arrhythmia.

Pulmonary:

  • No suspected, diffuse idiopathic interstitial lung disease or history of pulmonary fibrosis.

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • 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
    • Arkansas
      • Springdale, Arkansas, United States, 72764
        • Highlands Oncology Group
    • Delaware
      • Newark, Delaware, United States, 19713
        • Helen F. Graham Cancer Center
    • Illinois
      • Galesburg, Illinois, United States, 61401
        • Medical & Surgical Specialists, LLC
    • Indiana
      • Bloomington, Indiana, United States, 47403
        • Cancer Care Center of Southern Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Simon Cancer Center
      • Muncie, Indiana, United States, 47303
        • Medical Consultants, P.C.
      • South Bend, Indiana, United States, 46601
        • Northern Indiana Cancer Research Consortium
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Siteman Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center
    • Pennsylvania
      • Rockledge, Pennsylvania, United States, 19046
        • Fox Chase Cancer Center Extramural Research Program

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

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed advanced solid organ malignancy that is refractory to currently available therapies or for which no effective therapy exists.
  • Must have measurable or evaluable disease per RECIST as evaluated by imaging within 30 days prior to registration for protocol therapy.
  • Must have completed chemotherapy at least 28 days prior to registration for protocol therapy and recovered from the acute toxic effects.
  • Prior radiation therapy is allowed to < 25% of the bone marrow. Patients must have recovered from the acute toxic effects of radiation prior to registration for protocol therapy.
  • Must be willing to consent to the blood sample collection for SNP analysis.
  • Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time of consent until at least 30 days following completion of protocol therapy.
  • Females of childbearing potential must have a negative pregnancy test within 7 days prior to registration for protocol therapy. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
  • Written informed consent and HIPAA authorization for release of personal health information.
  • Age > 18 years.

Exclusion Criteria:

  • No prior therapy with cyclophosphamide or anthracyclines.
  • No treatment with any investigational agent within 28 days prior to registration for protocol therapy.
  • No suspected, diffuse idiopathic interstitial lung disease or history of pulmonary fibrosis.
  • No evidence of severe or uncontrolled other systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol.
  • No symptomatic brain metastases. Patients with treated brain metastasis must be off steroids and must have completed radiation at least 21 days prior to registration for protocol therapy.

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 1

Amrubicin + Cyclophosphamide 3+3 design with the following dose levels:

Dose Level -1: Amrubicin 20mg/m2, Cyclophosphamide 500mg/m2

Dose Level 1: Amrubicin 25mg/m2, Cyclophosphamide 500mg/m2

Dose Level 2: Amrubicin 30mg/m2, Cyclophosphamide 500mg/m2

Dose Level 3: Amrubicin 35mg/m2, Cyclophosphamide 500mg/m2

Dose Level 4: Amrubicin 40mg/m2, Cyclophosphamide 500mg/m2
Drug: Amrubicin
  • Dose Level -1: 20mg/m2
  • Dose Level 1: 25mg/m2
  • Dose Level 2: 30mg/m2
  • Dose Level 3: 35mg/m2
  • Dose Level 4: 40mg/m2

Amrubicin will be given as a slow IV push or infusion over approximately 5 minutes once daily for 3 consecutive days starting on day 1 of each 21 day cycle.

Drug: Cyclophosphamide
Cyclophosphamide will be given at a fixed dose as 500mg/m2 IV infusion over 30-60 minutes on day 1 of each 21 day cycle (following amrubicin).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of the combination of amrubicin and cyclophosphamide in patients with advanced solid tumors.
Time Frame: 24 months
24 months

Secondary Outcome Measures

Outcome Measure
Time Frame
To determine the toxicities of the combination of amrubicin and cyclophosphamide in patients with advanced solid tumors.
Time Frame: 24 months
24 months
To assess response to the combination of amrubicin and cyclophosphamide
Time Frame: 24 months
24 months

Collaborators and Investigators

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

Sponsor

Lawrence Einhorn

Collaborators

Hoosier Cancer Research Network
Celgene Corporation

Investigators

  • Principal Investigator: Lawrence Einhorn, M.D., Hoosier Cancer Research Network

Publications and helpful links

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

General Publications

Helpful Links

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

March 1, 2009

Primary Completion (ACTUAL)

July 1, 2010

Study Completion (ACTUAL)

July 1, 2010

Study Registration Dates

First Submitted

April 29, 2009

First Submitted That Met QC Criteria

April 29, 2009

First Posted (ESTIMATE)

April 30, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

December 23, 2015

Last Update Submitted That Met QC Criteria

December 21, 2015

Last Verified

December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HOG LUN07-130

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.

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