A Phase 2 interventional study of Laboratory Biomarker Analysis and Rilotumumab in Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma and Recurrent Primary Peritoneal Carcinoma, sponsored by Gynecologic Oncology Group. Completed at 28 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-09-07.
Sponsored by Gynecologic Oncology Group · Phase 2, Interventional, and Treatment
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.
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.
6,745 studies on the registry are indexed under Carcinoma; 1,163 are open to participants now.
This study's enrollment of 31 is below the median of 45 across 5,174 interventional studies indexed under Carcinoma.
Browse Carcinoma studies →Gynecologic Oncology Group is the lead sponsor of 181 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Patients who have received one prior regimen must have a GOG performance status of 0, 1, or 2
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
Exclusion Criteria:
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 · Biological: Rilotumumab
Correlative studies
Given IV
Also known as: AMG 102, Anti-HGF Monoclonal Antibody AMG 102, Fully Human Anti-HGF Monoclonal Antibody AMG 102
Proportion of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.1
Complete and Partial Tumor Response by RECIST 1.1. RECIST 1.1 defines complete response as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm and the disappearance of all non-target lesions and normalization of tumor marker level. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.
Time frame: CT scan or MRI if used to follow lesion for measurable disease every other cycle during treatment then every 3 months thereafter until disease progression is confirmed; also repeat at any time if clinically indicated up to 5 years.
Progression-free Survival > 6 Months Using RECIST 1.0
Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression was based on RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.
Time frame: CT scan or MRI if used to follow lesion for measurable disease every other cycle during treatment then every 3 months thereafter until disease progression is confirmed; up to 6 months.
Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 4.0
Number of participants with a maximum grade of 3 or higher during the treatment period.
Time frame: Assessed every cycle while on treatment, 30 days after the last cycle of treatment
Duration of Overall Survival (OS)
Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
Time frame: Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.
Duration of Progression-free Survival (PFS)
Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression was based on RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.
Time frame: CT scan or MRI if used to follow lesion for measurable disease every other cycle during treatment then every 3 months thereafter until disease progression is confirmed; also repeat at any time if clinically indicated up to 5 years.
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.
Time frame: Baseline
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).
Time frame: Up to 1 day prior to course 2
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).
Time frame: Up to 1 day prior to course 2
This trial was opened to patient entry on October 10, 2010 and was closed to accrual on May 10, 2011.
| Milestone | AMG 102 |
|---|---|
| Started | 31 |
| Completed | 31 |
| Not completed | 0 |
Complete and Partial Tumor Response by RECIST 1.1. RECIST 1.1 defines complete response as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm and the disappearance of all non-target lesions and normalization of tumor marker level. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.
| participants | AMG 102 |
|---|---|
| Partial response | 0 |
| Complete response | 1 |
Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression was based on RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.
| participants | AMG 102 |
|---|---|
| Patient with PFS>6 Months | 2 |
| Patients with PFS<6 months | 29 |
Number of participants with a maximum grade of 3 or higher during the treatment period.
| participants | AMG 102 |
|---|---|
| Leukopenia | 1 |
| Neutropenia | 1 |
| Cardiac | 1 |
| Nausea | 2 |
| Vomiting | 4 |
| Other Gastrointestinal | 7 |
| General and administration site | 4 |
| Hepatobiliary | 1 |
| Infections/infestations | 2 |
| Metabolism/nutrition | 5 |
| Respiratory/thoracic/mediastinal | 1 |
| Skin/subcutaneous | 1 |
| Vascular disorders | 2 |
Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
| months | AMG 102 |
|---|---|
| Duration of Overall Survival (OS) | 4.3 (1.9 to 5.8) |
Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression was based on RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.
| months | AMG 102 |
|---|---|
| Duration of Progression-free Survival (PFS) | 1.8 (1.7 to 1.9) |
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.
Results for this outcome have not been posted.
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).
Results for this outcome have not been posted.
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).
Results for this outcome have not been posted.
Collected over Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| AMG 102 | 14/31 (45.2%) | 14/31 (45.2%) | 31/31 (100%) |
| Event | AMG 102 |
|---|---|
| VomitingGastrointestinal disorders | 3/31 |
| Abdominal PainGastrointestinal disorders | 3/31 |
| Death NosGeneral disorders | 3/31 |
| Pleural EffusionRespiratory, thoracic and mediastinal disorders | 2/31 |
| DiarrheaGastrointestinal disorders | 1/31 |
| Small Intestinal ObstructionGastrointestinal disorders | 1/31 |
| Gastrointestinal Disorders - OtherGastrointestinal disorders | 1/31 |
| AscitesGastrointestinal disorders | 1/31 |
| FallInjury, poisoning and procedural complications | 1/31 |
| HyperglycemiaMetabolism and nutrition disorders | 1/31 |
| Event | AMG 102 |
|---|---|
| AnemiaBlood and lymphatic system disorders | 20/31 |
| FatigueGeneral disorders | 19/31 |
| NauseaGastrointestinal disorders | 14/31 |
| VomitingGastrointestinal disorders | 11/31 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 9/31 |
| ConstipationGastrointestinal disorders | 8/31 |
| HypomagnesemiaMetabolism and nutrition disorders | 8/31 |
| AnorexiaMetabolism and nutrition disorders | 8/31 |
| Peripheral Sensory NeuropathyNervous system disorders | 8/31 |
| Edema LimbsGeneral disorders | 7/31 |
Eligible and treated patients.
| Age, Customized(participants) | AMG 102 |
|---|---|
| 40-49 years | 4 |
| 50-59 years | 6 |
| 60-69 years | 9 |
| 70-79 years | 10 |
| 80-89 years | 2 |
| Sex: Female, Male(Participants) | AMG 102 |
|---|---|
| Female | 31 |
| Male | 0 |
| Race (NIH/OMB)(Participants) | AMG 102 |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 4 |
| White | 27 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
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