Amrubicin + Cyclophosphamide in Advanced Solid Organ Malignancies

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00890955
• Other study ID #: HOG LUN07-130
• Status: Completed
• Phase: Phase 1
• First received: April 29, 2009
• Last updated: December 21, 2015
• Start date: March 2009
• Est. completion date: July 2010

Study information

• Verified date: December 2015
• Source: Hoosier Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: July 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung Cancer

Intervention

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.
• 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).

Locations

Country	Name	City	State
United States	Cancer Care Center of Southern Indiana	Bloomington	Indiana
United States	Medical & Surgical Specialists, LLC	Galesburg	Illinois
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	Medical Consultants, P.C.	Muncie	Indiana
United States	Helen F. Graham Cancer Center	Newark	Delaware
United States	Providence Portland Medical Center	Portland	Oregon
United States	Fox Chase Cancer Center Extramural Research Program	Rockledge	Pennsylvania
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	Highlands Oncology Group	Springdale	Arkansas
United States	Siteman Cancer Center	St. Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
Lawrence Einhorn	Celgene Corporation, Hoosier Cancer Research Network

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. 2014 Dec — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		24 months	Yes
Secondary	To determine the toxicities of the combination of amrubicin and cyclophosphamide in patients with advanced solid tumors.		24 months	Yes
Secondary	To assess response to the combination of amrubicin and cyclophosphamide		24 months	No

External Links

•   Hoosier Oncology Group Homepage