Clinical trial NCT00890955: Amrubicin + Cyclophosphamide in Advanced Solid Organ Malignancies
Official title: A Phase I Study of Amrubicin and Cyclophosphamide in Patients With Advanced Solid Organ Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lung Cancer
Keywords: Solid tumors
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
name: Hoosier Cancer Research Network
First posted: 2009-04-30
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: 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.
timeFrame: 24 months
Secondary outcomes:
measure: To determine the toxicities of the combination of amrubicin and cyclophosphamide in patients with advanced solid tumors.
timeFrame: 24 months
measure: To assess response to the combination of amrubicin and cyclophosphamide
timeFrame: 24 months
Other outcomes:
Locations:
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Newark
country: United States
facility: Helen F. Graham Cancer Center
state: Delaware
city: Galesburg
country: United States
facility: Medical & Surgical Specialists, LLC
state: Illinois
city: Bloomington
country: United States
facility: Cancer Care Center of Southern Indiana
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Muncie
country: United States
facility: Medical Consultants, P.C.
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: St. Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Rockledge
country: United States
facility: Fox Chase Cancer Center Extramural Research Program
state: Pennsylvania
Study officials:
affiliation: Hoosier Cancer Research Network
name: Lawrence Einhorn, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.