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

Recurrent Ovarian Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01039207
• Other study ID #: GOG-0170P
• Secondary ID: NCI-2011-01996CD
• Status: Completed
• Phase: Phase 2
• First received: December 22, 2009
• Last updated: February 9, 2016
• Start date: October 2010
• Est. completion date: July 2014

Study information

• Verified date: February 2016
• Source: Gynecologic Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: July 2014
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Carcinoma
• Fallopian Tube Neoplasms
• Ovarian Neoplasms
• Recurrent Fallopian Tube Carcinoma
• Recurrent Ovarian Carcinoma
• Recurrent Primary Peritoneal Carcinoma

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies

Biological:
• Rilotumumab
Given IV

Locations

Country	Name	City	State
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio
United States	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Case Western Reserve University	Cleveland	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Duke University Medical Center	Durham	North Carolina
United States	Baylor All Saints Medical Center at Fort Worth	Fort Worth	Texas
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Lake University Ireland Cancer Center	Mentor	Ohio
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Florida Hospital Orlando	Orlando	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Carilion Clinic Gynecological Oncology	Roanoke	Virginia
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Gynecologic Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biomarker panel from tumor tissue	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.	Baseline	No
Other	Circulating levels of HGF/scatter factor (SF)	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).	Up to 1 day prior to course 2	No
Other	Circulating levels of markers of angiogenesis	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).	Up to 1 day prior to course 2	No
Primary	Frequency of patients who survive progression-free for at least 6 months after study entry or have objective tumor response		6 months	No
Secondary	Duration of OS	Will be characterized with Kaplan-Meier plots and estimates of the median time until death.	Duration of time from study entry to time of death or the date of last contact, assessed up to 5 years	No
Secondary	Duration of PFS	Will be characterized with Kaplan-Meier plots and estimates of the median time until progression.	Duration of time from study entry to time of progression or death, whichever occurs first, assessed up to 5 years	No
Secondary	Frequency and severity of adverse effects as assessed by the NCI CTCAE	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.	Up to 5 years	Yes