Clinical trial NCT00719212: Study of AMG 479 as Second Line Therapy in Patients With Recurrent Platinum-sensitive Ovarian Cancer
Official title: A Multicenter Open Label Phase II Study of the Efficacy and Safety of AMG 479, a Fully Human Monoclonal Antibody Against Insulin-like Growth Factor Type 1 Receptor (IGF-1R) as Second Line Therapy in Patients With Recurrent Platinum Sensitive Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Neoplasms
Lead sponsor: Translational Research in Oncology
Sponsor class: OTHER
First posted: 2008-07-21
Enrollment: 61
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to obtain an estimate of the objective response rate (ORR) of AMG 479 in patients with recurrent platinum-sensitive ovarian epithelial (including fallopian tube and primary peritoneal) carcinoma failing frontline chemotherapy.


Eligibility criteria: Inclusion Criteria:

* Histologically-confirmed ovarian epithelial (including fallopian tube and primary peritoneal) carcinoma. Baseline paraffin embedded tissue from the patient's primary diagnosis is requested before study enrollment and should be forwarded to the designated central laboratory. In patients with measurable disease or sufficient ascites, fresh frozen tissue or ascites fluid should be obtained by needle biopsy and submitted to the designated central laboratory.
* Prior treatment with at most 1 treatment regimen in the primary treatment setting.
* Platinum-sensitive disease defined by recurrence or progression of disease \> 6 months AND \< 24 months after completion of prior platinum based chemotherapy.
* Female \> 18 years of age or legal age.
* ECOG performance status ≤ 1.
* Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Subjects with non-measurable disease with a biochemical recurrence are eligible provided the CA 125 is elevated by more than 2 times the upper limits of normal, confirmed in two successive samples, drawn at least one week apart.
* Resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE v.3.0 Grade ≤ 1 and to baseline laboratory values as defined in the inclusion criterion immediately below.
* Adequate organ and bone marrow function
* Nondiabetic patients or Type 1 or 2 Diabetic Patients controlled with HgbA1c \< 8% and fasting blood glucose level \<160 mg/dL
* Adequate coagulation parameters (within 21 days prior to registration), International Normalized Ratio (INR) ≤1.5; Activated ProThrombin Time (APTT) ≤ 1.5 x ULN.

Exclusion Criteria:

* More than 1 prior chemotherapy regimen in the treatment of ovarian cancer.
* Platinum-resistant disease as defined by a recurrence or progression less or equal to six months after completion of the frontline platinum based chemotherapy.
* Anticipation of a need for a major surgical procedure (e.g., impending bowel obstruction, gastrointestinal perforation) or radiation therapy during the trial.
* Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or for in situ carcinoma of the cervix uteri.
* 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.
* History of hypersensitivity to recombinant proteins.
* Prior treatment with a humanized monoclonal antibody.
* Treatment with chemotherapy, radiotherapy, surgery, blood products, or an investigational agent within 3 weeks of trial enrolment.
* Any of the following within 6 months prior to trial registration: 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, 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 evidently 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.
* Mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the trial.
* Refusal or inability to give informed consent to participate in the trial.
* 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 trial results, and in the judgment of the investigator would make the patient inappropriate for entry into this trial.

Primary outcomes:
measure: Objective Response Rate (ORR) Investigator Assessment: % of Patients in the Group Who Achieve a Complete Response(CR) or Partial Response(PR) According to RECIST Criteria and GCIG CA125 Response Criteria. - Assessments of the Response by the Investigators
timeFrame: Radiological Tumor assessment: Every 9 (+/- 1 ) weeks during study treatment until documentation of progression or end of study treatment + confirmation PR or CR no less than 4 weeks after initial documentation of response + CA 125: Day 1 of each cycle
measure: Objective Response Rate (ORR) Independent Radiology Committee % of Patients in the Group Who Achieve a Complete or Partial Response According to RECIST Criteria and GCIG CA 125 Response Criteria.
timeFrame: Radiological Tumor assessment: Every 9 (+/- 1 ) weeks during study treatment until documentation of progression or end of study treatment + confirmation PR or CR no less than 4 weeks after initial documentation of response + CA 125: Day 1 of each cycle
Secondary outcomes:
measure: Time To Progression (TTP) Investigator Assessment
timeFrame: Every 9 (+/- 1 ) weeks during study treatment until documentation of progression or end of study treatment + confirmation PR or CR no less than 4 weeks after initial documentation of response
measure: Clinical Benefit Rate (CBR) Investigator Assessmt % of Patients in the gp Who Achieve a Complete Response-CR,Partial Response-PR or Stable Disease-SD for 16wks From Registrat° Considering the Global Response Combining RECIST Criteria and CA125 Assessmts
timeFrame: At 16 weeks from registration
measure: Overall Survival (OS) Investigator Assessment
timeFrame: Day 1 of each cycle during study treatment + follow-up every 6 months for the first 3 years in the study or until death whichever occurs first
measure: Time To Marker Progression (TTMP) Investigator Assessment - Interval Form the Date of Registration to the Date of Disease Progression as Per GCIG 2005 Definition of CA 125 Progression.
timeFrame: Day 1 of each cycle
measure: Progression-free Survival (PFS) Investigator Assessment - Interval From Registration to Disease Progression or Death Due to Any Cause - According to RECIST and CA 125
timeFrame: Every 9 (+/- 1 ) weeks during study treatment until documentation of progression or end of study treatment + confirmation PR or CR no less than 4 weeks after initial documentation of response
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer 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: LAC/USC Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California/ Norris Comprehensive Cancer Center
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: Pasadena
country: United States
facility: Central Hematology Oncology Medical Group Inc.
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Ann arbor
country: United States
facility: St Joseph Mercy Health System
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Henderson
country: United States
facility: Comprehensive Cancer Centre of Nevada
state: Nevada
city: Calgary
country: Canada
facility: Tom Baker Centre
city: Hamilton
country: Canada
facility: Juravinski Cancer Center
city: Montreal
country: Canada
facility: CHUM Hôpital Notre Dama
city: Montreal
country: Canada
facility: Jewish General Hospital
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Départemental Les Oudairies
city: Lyon
country: France
facility: Centre Léon Berard
city: Neuilly sur Seine
country: France
facility: Clinique Hartmann
city: Paris
country: France
facility: Institut Curie
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charité Campus Benjamin Franklin
city: Erlangen
country: Germany
facility: Universitatsklinikum Erlangen
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg Eppendorf
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Dublin
country: Ireland
facility: Mater Private Hospital
city: Dublin
country: Ireland
facility: St Jame's Hospital
city: Waterford
country: Ireland
facility: Waterford Regional Hospital
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: La Laguna (Santa Cruz de Tenerife)
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
Study officials:
affiliation: University of California, Los Angeles
name: Gottfried E Konecny, MD
role: STUDY_CHAIR
References: