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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Translational Research in Oncology
ClinicalTrials.gov Identifier:
NCT00719212
First received: July 18, 2008
Last updated: December 8, 2015
Last verified: December 2015
  Purpose
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.

Condition Intervention Phase
Ovarian Neoplasms
Biological: AMG 479
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Translational Research in Oncology:

Primary Outcome Measures:
  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]

    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

  • 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. [ Time Frame: 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 ] [ Designated as safety issue: No ]

    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


Secondary Outcome Measures:
  • Time To Progression (TTP) Investigator Assessment [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: At 16 weeks from registration ] [ Designated as safety issue: No ]

    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

  • Overall Survival (OS) Investigator Assessment [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Interval between the date of registration and the date of death

  • 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. [ Time Frame: Day 1 of each cycle ] [ Designated as safety issue: No ]

    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.

  • Progression-free Survival (PFS) Investigator Assessment - Interval From Registration to Disease Progression or Death Due to Any Cause - According to RECIST and CA 125 [ Time Frame: 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 ] [ Designated as safety issue: No ]

    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


Enrollment: 61
Study Start Date: January 2009
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AMG 479
AMG 479 administered on day 1 of each 21-day cycle up to disease progression, unacceptable toxicity, withdrawal of consent or sponsor decision to stop the study.
Biological: AMG 479
Solution for infusion - 18 mg/kg on day 1 of each 21-day cycle

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00719212

  Show 37 Study Locations
Sponsors and Collaborators
Translational Research in Oncology
Investigators
Study Chair: Gottfried E Konecny, MD University of California, Los Angeles
  More Information

Responsible Party: Translational Research in Oncology
ClinicalTrials.gov Identifier: NCT00719212     History of Changes
Other Study ID Numbers: TRIO 015 
Study First Received: July 18, 2008
Results First Received: October 22, 2015
Last Updated: December 8, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Ireland: Health Products Regulatory Authority
Israel: Israeli Health Ministry Pharmaceutical Administration

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 06, 2016