Rilotumumab in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Gynecologic Oncology Group
ClinicalTrials.gov Identifier:
NCT01039207
First received: December 22, 2009
Last updated: February 9, 2016
Last verified: February 2016
  Purpose
This phase II trial studies how well rilotumumab works in treating patients with ovarian epithelial, fallopian tube, or primary peritoneal cancer that has failed to respond to other therapies (persistent) or has returned after a period of improvement (recurrent). Rilotumumab is a type of drug called a monoclonal antibody, and may interfere with the ability of tumor cells to grow and spread by targeting certain cells and blocking them from working.

Condition Intervention Phase
Recurrent Fallopian Tube Carcinoma
Recurrent Ovarian Carcinoma
Recurrent Primary Peritoneal Carcinoma
Other: Laboratory Biomarker Analysis
Biological: Rilotumumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Evaluation of AMG 102 (Rilotumumab) (NSC #750009) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma

Resource links provided by NLM:


Further study details as provided by Gynecologic Oncology Group:

Primary Outcome Measures:
  • Frequency of patients who survive progression-free for at least 6 months after study entry or have objective tumor response [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of OS [ Time Frame: Duration of time from study entry to time of death or the date of last contact, assessed up to 5 years ] [ Designated as safety issue: No ]
    Will be characterized with Kaplan-Meier plots and estimates of the median time until death.

  • Duration of PFS [ Time Frame: Duration of time from study entry to time of progression or death, whichever occurs first, assessed up to 5 years ] [ Designated as safety issue: No ]
    Will be characterized with Kaplan-Meier plots and estimates of the median time until progression.

  • Frequency and severity of adverse effects as assessed by the NCI CTCAE [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    The frequency and severity of adverse events will be tabulated by the nature of the adverse events (often related to the organ or organ system) and the worst grade of toxicity experienced by each patient while participating on study. Exceptionally frequent or severe adverse events will be examined more carefully.


Other Outcome Measures:
  • Biomarker panel from tumor tissue [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    A panel of biomarkers from fixed and embedded tumor tissue will be tested for association with measures of response to treatment including PFS and OS.

  • Circulating levels of HGF/scatter factor (SF) [ Time Frame: Up to 1 day prior to course 2 ] [ Designated as safety issue: No ]
    Exploratory analyses will be conducted to assess the possible effects of the study regimen on the biomarkers of interest as well as associations between the biomarkers and clinical outcome (such as PFS and OS).

  • Circulating levels of markers of angiogenesis [ Time Frame: Up to 1 day prior to course 2 ] [ Designated as safety issue: No ]
    Exploratory analyses will be conducted to assess the possible effects of the study regimen on the biomarkers of interest as well as associations between the biomarkers and clinical outcome (such as PFS and OS).


Enrollment: 31
Study Start Date: October 2010
Study Completion Date: July 2014
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (rilotumumab)
Patients receive rilotumumab IV over 30-60 minutes on days 1 and 14. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Tumor tissue and blood samples may be collected periodically for further laboratory analysis.
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Rilotumumab
Given IV
Other Names:
  • AMG 102
  • Anti-HGF Monoclonal Antibody AMG 102
  • Fully Human Anti-HGF Monoclonal Antibody AMG 102

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the proportion of patients who survive progression-free for at least 6 months and the proportion of patients who have objective tumor response (complete or partial) in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.

SECONDARY OBJECTIVES:

I. To determine the frequency and severity of adverse events associated with treatment with AMG 102 (rilotumumab) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).

II. To determine the duration of progression-free survival (PFS) and overall survival (OS).

TERTIARY OBJECTIVES:

I. To explore the association between a panel of biomarkers (as assayed by immunohistochemistry and mutation analysis) and measures of response to treatment with AMG 102 (rilotumumab) and clinical outcome in archived tumor tissue.

II. To evaluate circulating pre- and post-treatment levels of hepatocyte growth factor/scatter factor and markers of angiogenesis and their association with response to treatment with AMG 102 (rilotumumab) and clinical outcome.

OUTLINE:

Patients receive rilotumumab intravenously (IV) over 30-60 minutes on days 1 and 14. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma; histologic confirmation of the original primary tumor is required via the pathology report
  • All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
  • Patient must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
  • Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG Phase III protocol for the same patient population
  • Patients who have received one prior regimen must have a GOG performance status of 0, 1, or 2

    • Patients who have received two prior regimens must have a GOG performance status of 0 or 1
  • Recovery from effects of recent surgery, radiotherapy, or chemotherapy
  • Major surgical procedures must have taken place > 30 days before enrollment; minor surgical procedures must have taken place > 14 days before enrollment; central venous catheter placement is allowed at any time prior to enrollment provided the patient has recovered and any surgical would has healed
  • Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infections [UTI])
  • Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration
  • Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued at least three weeks prior to registration
  • Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, high-dose therapy, consolidation, non-cytotoxic agents or extended therapy administered after surgical or non-surgical assessment
  • Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease according to the following definition:

    • Cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa

      • Note: Patients on this non-cytotoxic study are allowed to have received prior cytotoxic chemotherapy for management of recurrent or persistent disease, as defined above; however, patients are encouraged to enroll on second-line non-cytotoxic studies prior to receiving additional cytotoxic therapy
  • Patients who have received only one prior cytotoxic regimen (platinum-based regimen for management of primary disease), must have a platinum-free interval of less than 12 months, or have progressed during platinum-based therapy, or have persistent disease after a platinum-based therapy
  • Patients must NOT have received any non-cytotoxic therapy for management of recurrent or persistent disease; patients are allowed to receive, but are not required to receive, biologic (non-cytotoxic) therapy as part of their primary treatment regimen
  • Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl
  • Platelets greater than or equal to 100,000/mcl
  • Hemoglobin >= 9 g/dL
  • Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)
  • Bilirubin less than or equal to 1.5 x ULN
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) less than or equal to 3 x ULN
  • Alkaline phosphatase less than or equal to 2.5 x ULN
  • PTT (partial thromboplastin time) =< 1.5 x ULN
  • International normalized ratio (INR) =< 1.5 x ULN
  • Neuropathy (sensory and motor) less than or equal to CTCAE grade 1
  • Proteinuria: =< 1+ (urinalysis) or < 1 g/24 hrs (24 hour urine collection)
  • Patients must have signed an approved informed consent and authorization permitting release of personal health information
  • Patients must meet pre-entry requirements
  • Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing an effective form of contraception

Exclusion Criteria:

  • Patients who have had previous treatment with AMG 102 (rilotumumab) or other hepatocyte growth factor (HGF)/MET proto-oncogene, receptor tyrosine kinase (c-met) pathway inhibitors
  • Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies as noted, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
  • Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
  • Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
  • Patients with a past history of primary endometrial cancer are excluded unless all of the following conditions are met: stage not greater than I-B; no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other International Federation of Gynecology and Obstetrics (FIGO) grade 3 lesions
  • Patients with an active bleeding diathesis or on concurrent or prior (within 7 days of enrollment) therapeutic anti-coagulation therapy with warfarin, heparin, or low molecular weight heparin; the use of low-dose warfarin (=< 2 mg orally [PO] daily) for prophylaxis against central venous catheter thrombosis is allowed
  • Patients with serious intercurrent infections or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by this treatment
  • Patients who are pregnant or breastfeeding
  • Patients with psychiatric or other conditions rendering them incapable of participating in informed consent or the requirements of this protocol
  • Patients with a serious or non-healing wound
  • Patients with peripheral edema or lymphedema > grade 2
  • Patients with known positive human immunodeficiency virus (HIV) or hepatitis C or chronic or active hepatitis B
  • Patients with thromboembolic event or ischemic event within the past 12 months, such as deep venous thrombosis, pulmonary embolism, transient ischemic attack, cerebral infarction, or myocardial infarction
  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: NCT01039207

  Show 28 Study Locations
Sponsors and Collaborators
Gynecologic Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Lainie Martin NRG Oncology
  More Information

No publications provided

Responsible Party: Gynecologic Oncology Group
ClinicalTrials.gov Identifier: NCT01039207     History of Changes
Other Study ID Numbers: GOG-0170P  NCI-2011-01996  CDR0000662115  20070612  GOG-0170P  GOG-0170P  U10CA180868  U10CA027469 
Study First Received: December 22, 2009
Last Updated: February 9, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Fallopian Tube Neoplasms
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Ovarian Diseases
Urogenital Neoplasms
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 11, 2016