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

NCT00718523 | Terminated Phase 2 Results DMC

• 1 other identifier: TRIO 014
• Study Type: interventional
• Target: 170
• Locations: 8 countries
• Sites: 55

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.

Conditions

Ovarian Neoplasms

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Time To Progression (TTP): Interval From the Date of Randomization to the Date of Disease Progression

  Radiological tumor assessment: every 12 (+/- 1) weeks for 3 years after randomization + CA125: day 1 of each cycle

• Overall Survival (OS)

  Day 1 of each cycle up to 4 years after randomization

Study Arms (2)

A

PLACEBO COMPARATOR

Placebo plus paclitaxel/carboplatin chemotherapy administered on Day 1 of each 21-day cycle for 6 cycles - then 6 additional cycles of placebo administered on Day 1 of each 21-day cycle.

Drug: AMG 479 Placebo

B

EXPERIMENTAL

AMG 479 plus paclitaxel/carboplatin chemotherapy administered on Day 1 of each 21-day cycle for 6 cycles - then 6 additional cycles of AMG 479 single agent administered on Day 1 of each 21-day cycle.

Drug: AMG 479

Interventions

AMG 479 DRUG

Solution for infusion - 18 mg/kg on day 1 of each 21-day cycle

B

AMG 479 Placebo DRUG

Matching placebo administered Day 1 of each 21 day cycle.

A

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Translational Research in Oncology: lead

Study Sites (55)

Central Hematology Oncology Medical Group Inc.

Alhambra, California, 91801, United States

Location

Providence Saint Joseph Medical Center

Burbank, California, 91505, United States

Location

St Jude Heritage Healthcare

Fullerton, California, 92835, United States

Location

Wilshire Oncology Medical Group Inc

La Verne, California, 91750, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

UCLA

Los Angeles, California, 90095-1678, United States

Location

North Valley Hematology/Oncology Medical Group

Northridge, California, 91325, United States

Location

Ventura County Hematology-Oncology Specialists

Oxnard, California, 93030, United States

Location

University of California San Francisco

San Francisco, California, 94115, United States

Location

Central Coast Medical Oncology Corporation

Santa Maria, California, 93454, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

Memorial Cancer Institute

Hollywood, Florida, 33021, United States

Location

Florida Hospital Cancer Institute

Orlando, Florida, 32804, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Hematology and Oncology Specialists, LLC

Metairie, Louisiana, 70006, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, 89052, United States

Location

Hope A Women's Cancer Center

Asheville, North Carolina, 28806, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27104, United States

Location

The Toledo Hospital

Toledo, Ohio, 43606, United States

Location

University of Toledo

Toledo, Ohio, 43614, United States

Location

Cross Cancer Institute

Edmonton, Alberta, T6G1Z2, Canada

Location

London Health Science Center

London, Ontario, N6A4L6, Canada

Location

CHUM Hopital Notre Dame

Montreal, Quebec, H2L4M1, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

Centre Hospitalier Départemental Les Oudairies

La Roche-sur-Yon, 85925, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Clinique Hartmann

Neuilly-sur-Seine, 92200, France

Location

Institut Curie

Paris, 75005, France

Location

Charite Campus Benjamin Franklin

Berlin, 12200, Germany

Location

University Hospital Charite

Berlin, 13353, Germany

Location

Universitat Bonn

Bonn, 53105, Germany

Location

Universitatsklinikum Erlangen

Erlangen, 91054, Germany

Location

Universitatsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Universitatsklinikum des Saarlandes

Homburg, 66421, Germany

Location

Klinikum Kassel

Kassel, 34125, Germany

Location

Rotkreuzkrankenhaus Munchen

Munich, 80637, Germany

Location

Universitats Frauenklinik Tubingen

Tübingen, 72076, Germany

Location

St Jame's Hospital

Dublin, Ireland

Location

Waterford Regional Hospital

Waterford, Ireland

Location

Meir Medical Center

Kfar Saba, 44281, Israel

Location

Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Kaplan Medical Center

Rehovot, 76100, Israel

Location

Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Asaf Harofe MC

Zrifin, 70300, Israel

Location

Hospital Clinic i Provincial

Barcelona, 08036, Spain

Location

Hospital Universitario de Guadalajara

Guadalajara, 19002, Spain

Location

Hospital U 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario de Tenerife

San Cristóbal de La Laguna, 38320, Spain

Location

Hospital Universitario Virgen Macarena de Sevilla

Seville, 341071, Spain

Location

Saint James's University Hospital

Leeds, LS97TF, United Kingdom

Location

University College London

London, W1T4TJ, United Kingdom

Location

Mount Vernon cancer centre

Northwood, HA62RN, United Kingdom

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

ganitumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Results Point of Contact

• Title: Matthieu Rupin
• Organization: Translational Research In Oncology (formerly CIRG)

matthieu.rupin@trioncology.org

+331 58 10 08 89

Study Officials

• Gottfried E Konecny, MD

  University of California, Los Angeles

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2008
• First Posted: July 18, 2008
• Study Start: January 1, 2009
• Primary Completion: September 1, 2013
• Study Completion: November 1, 2014
• Last Updated: January 12, 2016
• Results First Posted: January 12, 2016

Record last verified: 2015-12

Locations

FR (4); DE (9); US (23); IE (2); GB (3); ES (5); CA (4); IL (5)