Study of Adding AMG 479 to First Line Chemotherapy in Patients With Optimally Debulked Epithelial Ovarian Cancer

Ovarian Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00718523
• Other study ID #: TRIO 014
• Status: Terminated
• Phase: Phase 2
• First received: July 17, 2008
• Last updated: December 8, 2015
• Start date: January 2009
• Est. completion date: November 2014

Study information

• Verified date: December 2015
• Source: Translational Research in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Paul-Ehrlich-InstitutFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Canada: Health CanadaSpain: Agencia Española de Medicamentos y Productos SanitariosIsrael: Israeli Health Ministry Pharmaceutical AdministrationIreland: Health Products Regulatory Authority
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 170
• Est. completion date: November 2014
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms, Glandular and Epithelial
• Ovarian Neoplasms

Intervention

Drug:
• AMG 479
Solution for infusion - 18 mg/kg on day 1 of each 21-day cycle
• AMG 479 Placebo
Matching placebo administered Day 1 of each 21 day cycle.

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	London Health Science Center	London	Ontario
Canada	CHUM Hopital Notre Dame	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
France	Centre Hospitalier Départemental Les Oudairies	La Roche Sur Yon
France	Centre Léon Bérard	Lyon
France	Clinique Hartmann	Neuilly Sur Seine
France	Institut Curie	Paris
Germany	Charite Campus Benjamin Franklin	Berlin
Germany	University Hospital Charite	Berlin
Germany	Universitat Bonn	Bonn
Germany	Universitatsklinikum Erlangen	Erlangen
Germany	Universitatsklinikum Hamburg Eppendorf	Hamburg
Germany	Universitatsklinikum des Saarlandes	Homburg
Germany	Klinikum Kassel	Kassel
Germany	Rotkreuzkrankenhaus Munchen	Munich
Germany	Universitats Frauenklinik Tubingen	Tubingen
Ireland	St Jame's Hospital	Dublin
Ireland	Waterford Regional Hospital	Waterford
Israel	Meir Medical Center	Kfar-Saba
Israel	Sheba Medical Center	Ramat Gan
Israel	Kaplan Medical Center	Rehovot
Israel	Sourasky Medical Center	Tel Aviv
Israel	Asaf Harofe MC	Zrifin
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital Universitario de Guadalajara	Guadalajara
Spain	Hospital Universitario de Tenerife	La Laguna
Spain	Hospital U 12 de Octubre	Madrid
Spain	Hospital Universitario Virgen Macarena de Sevilla	Sevilla
United Kingdom	Saint James's University Hospital	Leeds
United Kingdom	University College London	London
United Kingdom	Mount Vernon cancer centre	Northwood
United States	Central Hematology Oncology Medical Group Inc.	Alhambra	California
United States	Hope A Women's Cancer Center	Asheville	North Carolina
United States	Winship Cancer Institute Emory University School of Medicine	Atlanta	Georgia
United States	Providence Saint Joseph Medical Center	Burbank	California
United States	St Jude Heritage Healthcare	Fullerton	California
United States	Comprehensive Cancer Centers of Nevada	Henderson	Nevada
United States	Memorial Cancer Institute	Hollywood	Florida
United States	Wilshire Oncology Medical Group Inc	La Verne	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	UCLA	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Hematology and Oncology Specialists, LLC	Metairie	Louisiana
United States	Yale University School of Medicine	New Haven	Connecticut
United States	North Valley Hematology/Oncology Medical Group	Northridge	California
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	Ventura County Hematology-Oncology Specialists	Oxnard	California
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California San Francisco	San Francisco	California
United States	Central Coast Medical Oncology Corporation	santa Maria	California
United States	Moffitt Cancer Center	Tampa	Florida
United States	The Toledo Hospital	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Translational Research in Oncology

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Ireland,  Israel,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS): Time From Randomization Until Date of Progression or Death.	A patient may have been declared to have progressive disease on the basis of radiological measuremt of tumor lesions assessmt or CA125 evaluation (tumor measuremts taking precedence).Radiological progression was defined as per the RECIST guidelines (Therasse et al, JNCI2000) as at least 20% increase in the sum of the longest diameters of target lesions(ref the smallest sum of the longest diam recorded since the treatmt started or since the appearance of at least 1 new lesion).Serum CA125 progression was defined, according to the 2005 GCIG def: pts with: Elevated CA125 pretreatmt and normalization of CA125 has to show evidence of CA125= 2 times the upper normal limit on 2 occasions at least 1 wk apart OR; Elevated CA125 pretreatmt which never normalized must show evidence of CA125= 2 times the nadir value on 2 occasions at least 1 wk apart OR; CA125 in the normal range pretreatmt had to show evidence of CA125 = 2 times the upper normal limit on 2 occasions at least 1 wk apart	Radiological tumor assessment: every 12(+/- 1) weeks for 3 years after randomization + CA 125: day 1 of each cycle	No
Secondary	Time To Progression (TTP): Interval From the Date of Randomization to the Date of Disease Progression	A patient may have been declared to have progressive disease on the basis of radiological measuremt of tumor lesions assessmt or CA125 evaluation (tumor measuremts taking precedence).Radiological progression was defined as per the RECIST guidelines (Therasse et al, JNCI2000) as at least 20% increase in the sum of the longest diameters of target lesions(ref the smallest sum of the longest diam recorded since the treatmt started or since the appearance of at least 1 new lesion).Serum CA125 progression was defined, according to the 2005 GCIG def: pts with: Elevated CA125 pretreatmt and normalization of CA125 has to show evidence of CA125= 2 times the upper normal limit on 2 occasions at least 1 wk apart OR; Elevated CA125 pretreatmt which never normalized must show evidence of CA125= 2 times the nadir value on 2 occasions at least 1 wk apart OR; CA125 in the normal range pretreatmt had to show evidence of CA125 = 2 times the upper normal limit on 2 occasions at least 1 wk apart	Radiological tumor assessment: every 12 (+/- 1) weeks for 3 years after randomization + CA125: day 1 of each cycle	No
Secondary	Overall Survival (OS)	Interval between the date from randomization to death from any cause whichever came first.	Day 1 of each cycle up to 4 years after randomization	No