Study of AMG 479 as Second Line Therapy in Patients With Recurrent Platinum-sensitive Ovarian Cancer

Ovarian Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00719212
• Other study ID #: TRIO 015
• Status: Completed
• Phase: Phase 2
• First received: July 18, 2008
• Last updated: December 8, 2015
• Start date: January 2009
• Est. completion date: May 2013

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 AdministrationCanada: Health CanadaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Paul-Ehrlich-InstitutSpain: Agencia Española de Medicamentos y Productos SanitariosIreland: Health Products Regulatory AuthorityIsrael: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Neoplasms

Intervention

Biological:
• AMG 479
Solution for infusion - 18 mg/kg on day 1 of each 21-day cycle

Locations

Country	Name	City	State
Canada	Tom Baker Centre	Calgary
Canada	Juravinski Cancer Center	Hamilton
Canada	CHUM Hôpital Notre Dama	Montreal
Canada	Jewish General Hospital	Montreal
France	Centre Hospitalier Départemental Les Oudairies	La Roche Sur Yon
France	Centre Léon Berard	Lyon
France	Clinique Hartmann	Neuilly sur Seine
France	Institut Curie	Paris
France	Institut Gustave Roussy	Villejuif
Germany	Charité Campus Benjamin Franklin	Berlin
Germany	Universitatsklinikum Erlangen	Erlangen
Germany	Universitatsklinikum Hamburg Eppendorf	Hamburg
Ireland	Cork University Hospital	Cork
Ireland	Mater Misericordiae University Hospital	Dublin
Ireland	Mater Private Hospital	Dublin
Ireland	St Jame's Hospital	Dublin
Ireland	Waterford Regional Hospital	Waterford
Israel	Kaplan Medical Center	Rehovot
Spain	Hospital Universitario de Tenerife	La Laguna (Santa Cruz de Tenerife)
Spain	Hospital U 12 de Octubre	Madrid
Spain	Hospital Universitario Virgen Macarena de Sevilla	Sevilla
United States	St Joseph Mercy Health System	Ann arbor	Michigan
United States	University of Colorado	Aurora	Colorado
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	University of Chicago	Chicago	Illinois
United States	St Jude Heritage Healthcare	Fullerton	California
United States	Comprehensive Cancer Centre of Nevada	Henderson	Nevada
United States	Wilshire Oncology Medical Group Inc	La Verne	California
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	LAC/USC Medical Center	Los Angeles	California
United States	UCLA	Los Angeles	California
United States	University of Southern California/ Norris Comprehensive Cancer Center	Los Angeles	California
United States	North Valley Hematology/ Oncology Medical Group	Northridge	California
United States	Ventura County Hematology Oncology Specialists	Oxnard	California
United States	Central Hematology Oncology Medical Group Inc.	Pasadena	California
United States	Mayo Clinic	Rochester	Minnesota
United States	Cancer Center of Kansas	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Translational Research in Oncology

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	RECIST(v1.0):CR:disappearance of all target lesions or disappearance of all nontarget lesions & normalization of tumor marker level/•PR:at least 30% decrease in the sum of the longest diam(LD) of target les° taking as ref the baseline sum LD OR CR for target les° & incomplete response/SD for nontarget les°.; CR & PR to be confirmed no less than 4 wks after initial doc of response.The def of the resp acc to serum CA125 level was as per GCIGCA125 criteria: PR:elevated CA125 at baseline PR considered if a = 50% decrease compared to baseline value was observed on 2 consecutive assessmts drawn at least 1 wk apart; CR:elevated CA125 at baseline CR was def with 2 CA125 values below ULN observed on 2 consecutive assessmts drawn at least 1 wk apart A pt was considered to have a best overall resp of:CR:if CR as per RECIST & CA125 /-PR: if CR as per RECIST & PR as per CA125 OR CR as per RECIST and SD as per CA125 with elevated CA125 at baseline OR PR as per RECIST & CR/PR or SD as per CA125	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	No
Primary	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.	RECIST(v1.0):CR:disappearance of all target lesions or disappearance of all nontarget lesions & normalization of tumor marker level/•PR:at least 30% decrease in the sum of the longest diam(LD) of target les° taking as ref the baseline sum LD OR CR for target les° & incomplete response/SD for nontarget les°.; CR & PR to be confirmed no less than 4 wks after initial doc of response.The def of the resp acc to serum CA125 level was as per GCIGCA125 criteria: PR:elevated CA125 at baseline PR considered if a = 50% decrease compared to baseline value was observed on 2 consecutive assessmts drawn at least 1 wk apart; CR:elevated CA125 at baseline CR was def with 2 CA125 values below ULN observed on 2 consecutive assessmts drawn at least 1 wk apart A pt was considered to have a best overall resp of:CR:if CR as per RECIST & CA125 /-PR: if CR as per RECIST & PR as per CA125 OR CR as per RECIST and SD as per CA125 with elevated CA125 at baseline OR PR as per RECIST & CR/PR or SD as per CA125	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	No
Secondary	Time To Progression (TTP) Investigator Assessment	Interval from the date of registration to the date of disease progression Investigator assessment As per RECIST (v1.0), disease progression represented an increase of at least 20% in the sum of the longest diameter (SLD) of target lesions, taking as reference the smallest SLD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.	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	No
Secondary	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	RECIST(v1.0): CR:disappearance of all target les°&non-target les°&normalization of tumor marker level; PR:at least 30% decrease in the sum of the LD of target les°-ref the baseline sum LD OR CR for target les°&incomplete resp/SD for non target les°; SD:insufficient shrinkage for PR or increase for PD-ref the smallest sum LD since ttmt started or Persistence of one/more non-target les°or/&maintenance of tumor marker level above the normal; CA125 level: PR:elev of CA125 at baseline PR if a = 50% decrease compared to baseline value observed on 2 consec assessmts drawn at least 1 wk apart; CR:elev of CA125 at baseline CR 2 CA125 below ULN observed on 2 consec assessmts drawn at least 1 wk apart; SD:neither CR/PR nor PD; Best overall resp of : CR:if CR per RECIST & per CA125; PR:if CR per RECIST & PR per CA125 OR CR per RECIST and SD per CA125 with elev CA125 at baseline OR PR per RECIST & CR/PR or SD per CA125; SD:other cases not qualifying for progression-at least 24 wks	At 16 weeks from registration	No
Secondary	Overall Survival (OS) Investigator Assessment	Interval between the date of registration and the date of death	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	No
Secondary	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.	The GCIG criteria (November 2005) were used to define progressive disease, based on serum CA 125 levels, as follows: Patients with elevated CA 125 pretreatment and normalization of CA 125 needed to show evidence of CA 125 greater than, or equal to, two times the ULN on two occasions at least 1 week apart or; Patients with elevated CA 125 pretreatment, which never normalizes needed to show evidence of CA 125 greater than, or equal to, two times the nadir value on two occasions at least 1 week apart or; Patients with CA 125 in the normal range pretreatment needed to show evidence of CA 125 greater than, or equal to, two times the ULN on two occasions at least 1 week apart.	Day 1 of each cycle	No
Secondary	Progression-free Survival (PFS) Investigator Assessment - Interval From Registration to Disease Progression or Death Due to Any Cause - According to RECIST and CA 125	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	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	No