Amrubicin + Cyclophosphamide in Advanced Solid Organ Malignancies

This study has been completed.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by:
Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT00890955
First received: April 29, 2009
Last updated: April 28, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Drug: Amrubicin
Drug: Cyclophosphamide
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Amrubicin and Cyclophosphamide in Patients With Advanced Solid Organ Malignancies

Resource links provided by NLM:


Further study details as provided by Hoosier Cancer Research Network:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the toxicities of the combination of amrubicin and cyclophosphamide in patients with advanced solid tumors. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • To assess response to the combination of amrubicin and cyclophosphamide [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: March 2009
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00890955

Locations
United States, Arkansas
Highlands Oncology Group
Springdale, Arkansas, United States, 72764
United States, Delaware
Helen F. Graham Cancer Center
Newark, Delaware, United States, 19713
United States, Illinois
Medical & Surgical Specialists, LLC
Galesburg, Illinois, United States, 61401
United States, Indiana
Cancer Care Center of Southern Indiana
Bloomington, Indiana, United States, 47403
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Medical Consultants, P.C.
Muncie, Indiana, United States, 47303
Northern Indiana Cancer Research Consortium
South Bend, Indiana, United States, 46601
United States, Missouri
Siteman Cancer Center
St. Louis, Missouri, United States, 63110
United States, Oregon
Providence Portland Medical Center
Portland, Oregon, United States, 97213
United States, Pennsylvania
Fox Chase Cancer Center Extramural Research Program
Rockledge, Pennsylvania, United States, 19046
Sponsors and Collaborators
Hoosier Cancer Research Network
Celgene Corporation
Investigators
Principal Investigator: Lawrence Einhorn, M.D. Hoosier Cancer Research Network
  More Information

Additional Information:
No publications provided

Responsible Party: Lawrence Einhorn, M.D., Hoosier Oncology Group
ClinicalTrials.gov Identifier: NCT00890955     History of Changes
Other Study ID Numbers: HOG LUN07-130
Study First Received: April 29, 2009
Last Updated: April 28, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Hoosier Cancer Research Network:
Solid tumors

Additional relevant MeSH terms:
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Cyclophosphamide
Amrubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on July 26, 2014