Amrubicin + Cyclophosphamide in Advanced Solid Organ Malignancies

NCT ID: NCT00890955

Last Updated: 2015-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-03-31

Study Completion Date

2010-07-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Lung Cancer

Keywords

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Solid tumors

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Amrubicin

Intervention Type DRUG

* 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.

Cyclophosphamide

Intervention Type DRUG

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).

Interventions

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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.

Intervention Type 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).

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene Corporation

INDUSTRY

Sponsor Role collaborator

Hoosier Cancer Research Network

OTHER

Sponsor Role collaborator

Lawrence Einhorn

OTHER

Sponsor Role lead

Responsible Party

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Lawrence Einhorn

Sponsor-Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Lawrence Einhorn, M.D.

Role: PRINCIPAL_INVESTIGATOR

Hoosier Cancer Research Network

Locations

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Highlands Oncology Group

Springdale, Arkansas, United States

Site Status

Helen F. Graham Cancer Center

Newark, Delaware, United States

Site Status

Medical & Surgical Specialists, LLC

Galesburg, Illinois, United States

Site Status

Cancer Care Center of Southern Indiana

Bloomington, Indiana, United States

Site Status

Indiana University Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Medical Consultants, P.C.

Muncie, Indiana, United States

Site Status

Northern Indiana Cancer Research Consortium

South Bend, Indiana, United States

Site Status

Siteman Cancer Center

St Louis, Missouri, United States

Site Status

Providence Portland Medical Center

Portland, Oregon, United States

Site Status

Fox Chase Cancer Center Extramural Research Program

Rockledge, Pennsylvania, United States

Site Status

Countries

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United States

References

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Jalal SI, Hanna N, Zon R, Masters GA, Borghaei H, Koneru K, Badve S, Prasad N, Somaiah N, Wu J, Yu Z, Einhorn L. Phase I Study of Amrubicin and Cyclophosphamide in Patients With Advanced Solid Organ Malignancies: HOG LUN 07-130. Am J Clin Oncol. 2017 Aug;40(4):329-335. doi: 10.1097/COC.0000000000000160.

Reference Type RESULT
PMID: 25503432 (View on PubMed)

Related Links

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http://www.hoosieroncologygroup.org

Hoosier Oncology Group Homepage

Other Identifiers

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HOG LUN07-130

Identifier Type: -

Identifier Source: org_study_id