Clinical trial NCT00718523: Study of Adding AMG 479 to First Line Chemotherapy in Patients With Optimally Debulked Epithelial Ovarian Cancer
Official title: A Randomized, Double-blind, Placebo Controlled, Multi-center, Phase II Study of Adding AMG 479, a Fully Human Monoclonal Antibody Against Insulin-like Growth Factor Type 1 Receptor (IGF-1R) to First Line Chemotherapy in Patients With Optimally Debulked ( < 1 cm ) Epithelial Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ovarian Neoplasms
Lead sponsor: Translational Research in Oncology
Sponsor class: OTHER
First posted: 2008-07-18
Enrollment: 170
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will determine the value of adding AMG 479 (fully human monoclonal antibody against IGF-1R) to paclitaxel and carboplatin first line chemotherapy in patients with optimally debulked (\<1 cm) FIGO stage III and IV (positive pleural cytology only) ovarian epithelial (including fallopian tube and primary peritoneal) carcinoma.


Eligibility criteria: Inclusion Criteria:

* Histologically-confirmed optimally debulked (\< 1 cm) FIGO stage III or stage IV (positive pleural cytology only) ovarian epithelial (including fallopian tube and primary peritoneal) carcinoma.
* Patients should have undergone surgical debulking, by a surgeon experienced in the management of ovarian cancer, with the aim of maximal surgical cytoreduction. All patients must be optimally debulked as defined as having no residual tumor of greater than 1 cm in the post surgical setting.
* Patients with stage IV disease will be eligible if a positive pleural cytology is the only extra peritoneal disease.
* Paraffin block (or 10 - 20 unstained slides) and fresh frozen surgical/biopsy specimens of the primary tumor are required at baseline.
* No prior systemic treatment in the primary disease treatment setting.
* Female ≥ 18 years of age or legal age.
* ECOG performance status ≤ 2.
* Adequate organ and bone marrow function
* Non diabetic patients or Type 1 or 2 Diabetic Patients:

  • Diabetes must be controlled with HgbA1c \< 8% and fasting blood glucose level \<160 mg/dL.
* Patient must be willing and able to comply with scheduled visits, and all study procedures.
* Informed consent obtained.
* Patients should be able to commence systemic therapy within 6 weeks of cytoreductive surgery.
* Life expectancy \> 12 weeks.
* Adequate coagulation parameters (within 14 days prior to randomization), International Normalized Ratio (INR) ≤1.5; Activated Prothrombin Time (APTT) ≤ 1.5 x ULN

Exclusion Criteria:

* Non-epithelial ovarian cancer, including malignant mixed Mullerian tumors.
* Borderline tumors (tumors of low malignant potential).
* Planned intraperitoneal cytotoxic chemotherapy.
* Prior systemic anticancer therapy for ovarian cancer.
* Any previous radiotherapy to the abdomen or pelvis.
* Patients with synchronous primary endometrial carcinoma, or a past history of primary endometrial carcinoma, are excluded unless ALL of the following criteria for describing the endometrial carcinoma are met: Stage ≤ Ib, no more than superficial myometrial invasion, no lymphovascular invasion, not poorly differentiated (i.e., not Grade 3 or papillary serous or clear cell).
* Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri or curatively treated DCIS/LCIS, or non-melanoma or in situ melanoma skin cancer.
* Prior treatment with a humanized monoclonal antibody anticancer therapeutic.
* Prior treatment with investigational treatment targeted to IGF axis including, but not limited to, CP 751,871, IM-A12, RO4858696.
* Previous exposure to AMG 479.
* Anticipation of a need for a major surgical procedure or radiation therapy during the study.
* History of hypersensitivity to recombinant proteins.
* Treatment with radiotherapy, surgery, or an investigational agent within 4 weeks of randomization.
* Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, cerebrovascular accident or transient ischemic attack, grade \> 2 peripheral neuropathy, pulmonary embolism, deep vein thrombosis, or other thromboembolic event.
* History of brain metastases, spinal cord compression, or carcinomatous meningitis.
* Patient of child-bearing potential is pregnant (eg, positive human chorionic gonadotropin test) or is breast feeding.
* Patient of child-bearing potential is not willing to use adequate contraceptive precautions.
* Known active infection, or on antiretroviral therapy for HIV disease.
* Known positive test for chronic hepatitis B or C infection.
* Any other underlying physical or mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study.
* Refusal or inability to give informed consent to participate in the study.
* Other severe acute or chronic medical or psychiatric condition, or significant laboratory abnormality requiring further investigation that may cause undue risk for the patient's safety, inhibit protocol participation, or interfere with interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study

Primary outcomes:
measure: Progression Free Survival (PFS): Time From Randomization Until Date of Progression or Death.
timeFrame: Radiological tumor assessment: every 12(+/- 1) weeks for 3 years after randomization + CA 125: day 1 of each cycle
Secondary outcomes:
measure: Time To Progression (TTP): Interval From the Date of Randomization to the Date of Disease Progression
timeFrame: Radiological tumor assessment: every 12 (+/- 1) weeks for 3 years after randomization + CA125: day 1 of each cycle
measure: Overall Survival (OS)
timeFrame: Day 1 of each cycle up to 4 years after randomization
Other outcomes:
Locations:
city: Alhambra
country: United States
facility: Central Hematology Oncology Medical Group Inc.
state: California
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center
state: California
city: Fullerton
country: United States
facility: St Jude Heritage Healthcare
state: California
city: La Verne
country: United States
facility: Wilshire Oncology Medical Group Inc
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Northridge
country: United States
facility: North Valley Hematology/Oncology Medical Group
state: California
city: Oxnard
country: United States
facility: Ventura County Hematology-Oncology Specialists
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Hollywood
country: United States
facility: Memorial Cancer Institute
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute Emory University School of Medicine
state: Georgia
city: Metairie
country: United States
facility: Hematology and Oncology Specialists, LLC
state: Louisiana
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Asheville
country: United States
facility: Hope A Women's Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Toledo
country: United States
facility: The Toledo Hospital
state: Ohio
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: London
country: Canada
facility: London Health Science Center
state: Ontario
city: Montreal
country: Canada
facility: CHUM Hopital Notre Dame
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Départemental Les Oudairies
city: Lyon
country: France
facility: Centre Léon Bérard
city: Neuilly Sur Seine
country: France
facility: Clinique Hartmann
city: Paris
country: France
facility: Institut Curie
city: Berlin
country: Germany
facility: Charite Campus Benjamin Franklin
city: Berlin
country: Germany
facility: University Hospital Charite
city: Bonn
country: Germany
facility: Universitat Bonn
city: Erlangen
country: Germany
facility: Universitatsklinikum Erlangen
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg Eppendorf
city: Homburg
country: Germany
facility: Universitatsklinikum des Saarlandes
city: Kassel
country: Germany
facility: Klinikum Kassel
city: Munich
country: Germany
facility: Rotkreuzkrankenhaus Munchen
city: Tubingen
country: Germany
facility: Universitats Frauenklinik Tubingen
city: Dublin
country: Ireland
facility: St Jame's Hospital
city: Waterford
country: Ireland
facility: Waterford Regional Hospital
city: Kfar-Saba
country: Israel
facility: Meir Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Zrifin
country: Israel
facility: Asaf Harofe MC
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Guadalajara
country: Spain
facility: Hospital Universitario de Guadalajara
city: La Laguna
country: Spain
facility: Hospital Universitario de Tenerife
city: Madrid
country: Spain
facility: Hospital U 12 de Octubre
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena de Sevilla
city: Leeds
country: United Kingdom
facility: Saint James's University Hospital
city: London
country: United Kingdom
facility: University College London
city: Northwood
country: United Kingdom
facility: Mount Vernon cancer centre
Study officials:
affiliation: University of California, Los Angeles
name: Gottfried E Konecny, MD
role: STUDY_CHAIR
References: