Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer
Conditions
Keywords
fallopian tube cancer, recurrent ovarian epithelial cancer, primary peritoneal cavity cancer
Brief summary
RATIONALE: AMG 706 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well AMG 706 works in treating patients with persistent or recurrent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.
Detailed description
OBJECTIVES: Primary * To assess the activity of AMG 706, in terms of the frequency of patients with progression-free survival for at least 6 months after initiating therapy or with an objective tumor response, in patients with persistent or recurrent ovarian epithelial, fallopian tube, or primary peritoneal carcinoma. Secondary * To determine the frequency and severity of adverse events as assessed by CTCAE v3.0. * To characterize the distribution of the progression-free and overall survival of these patients. OUTLINE: This is a multicenter study. Patients receive oral AMG 706 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.
Interventions
Sponsors
National Cancer Institute (NCI)
Gynecologic Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal carcinoma * Recurrent or persistent disease * Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan * Must have at least one target lesion that can be used to assess response, as defined by RECIST criteria * Tumors within a previously irradiated field will be designated as non-target lesions unless progression is documented OR a biopsy is obtained to confirm persistent disease ≥ 90 days following completion of radiotherapy * Must have received one prior platinum-based chemotherapeutic regimen containing carboplatin, cisplatin, or another organoplatinum compound for management of primary disease * Initial treatment may have included high-dose therapy, consolidation therapy, or extended therapy administered after surgical or non-surgical assessment * One additional cytotoxic regimen for management of recurrent or persistent disease allowed * Patients must have a platinum-free interval of \< 12 months, have progressed during platinum-based therapy, or have persistent disease after a platinum-based therapy * Ineligible for a higher priority GOG protocol * No pleural effusion or ascites causing grade 2 or greater dyspnea * No history of uncontrolled CNS metastases * Patients with a history of CNS metastases must have their disease controlled by radiotherapy and/or surgery; have at least two imaging scans following treatment (that were no less than 30 days apart) showing no progression of any lesions and no new lesions; and be clinically stable off corticosteroids for ≥ 14 days prior to study randomization PATIENT CHARACTERISTICS: * GOG performance status (PS) 0-2\* NOTE: \*Patients who have received 2 prior regimen must have a GOG PS of 0-2 and patients who have received 2 prior regimens must have a GOG PS of 0-1 * ANC ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Creatinine ≤ 1.5 times upper limit of normal (ULN) * Urine protein \< 30 mg/dL by urinalyses or ≤ 1+ by urine dipstick (unless quantitative protein is \< 500 mg by 24-hour urine collection) * Bilirubin ≤ 1.5 times ULN (\< 3 times ULN in patients with UGT1A1 promoter polymorphism \[i.e., Gilbert syndrome\] confirmed by genotyping or Invader® UGT1A1 Molecular Assay) * AST and ALT ≤ 2.5 times ULN (5 times ULN if liver metastases are present) * Alkaline phosphatase ≤ 2 times ULN (5 times ULN if liver or bone metastases are present) * PTT normal * INR ≤ 1.5 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Able to swallow oral medications * Cardiac ejection fraction normal * No sensory and motor neuropathy \> grade 2 * No other invasive malignancies within the past 5 years, except nonmelanoma skin cancer or other specific malignancies * No bleeding diathesis or hypercoagulopathy within the past 14 days * No arterial or venous thrombosis within the past 12 months * None of the following within the past 12 months: * Myocardial infarction * Cerebrovascular accident * Transient ischemic attack * Grade 2 or greater peripheral vascular disease * Percutaneous transluminal coronary angioplasty/stent * Congestive heart failure * Ongoing arrhythmias requiring medication * Unstable angina * No average systolic blood pressure ≥ 150 mm Hg and average diastolic blood pressure ≥ 90 mm Hg * Patients with hypertension that is stable on a current dose of anti-hypertensives are eligible * No history of impaired cardiac status (e.g., severe heart disease, cardiomyopathy, or congestive heart failure) * No psychiatric, addictive, or other kind of disorder that would compromise the ability of the patient to give written informed consent * No open wounds, ulcers, or fractures * No active infection requiring antibiotics (with the exception of uncomplicated UTI) * No known HIV, hepatitis B, or hepatitis C positivity * No known hypersensitivity to AMG 706 PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered form prior surgery, radiotherapy, or chemotherapy * At least 1 week since prior hormonal therapy for the malignant tumor * Concurrent hormone replacement therapy allowed * At least 3 weeks since other prior therapy directed at the malignant tumor, including biologic or immunologic agents (i.e., small molecules or murine monoclonal antibodies) * At least 12 weeks since prior chimeric, human, or humanized monoclonal antibodies * More than 30 days since prior investigational therapy * More than 12 weeks since prior bevacizumab * More than 30 days since prior VEGFR-targeted therapy, including, but not limited to, any of the following: * SU5416 * SU6668 * Sunitinib malate * Vandetanib * Vatalanib * AZD2171 * AEE 788 * Sorafenib * More than 28 days since prior major surgery * More than 14 days since prior minor surgery, including open breast biopsy * More than 7 days since prior core needle biopsy or placement of a central venous access device (including portion, tunneled, or non-tunneled catheters) * No prior cancer treatment that would contraindicate study therapy * No prior therapy AMG 706 * No prior chemotherapy for any abdominal or pelvic tumor other than for the treatment of ovarian, fallopian tube, or primary peritoneal cancer * Prior adjuvant chemotherapy for localized breast cancer allowed provided it was completed \> 3 years ago, and the patient remains free of recurrent or metastatic disease * No prior non-cytotoxic chemotherapy for management of recurrent or persistent disease * No prior radiotherapy to any portion of the abdominal cavity or pelvis other than for the treatment of ovarian, fallopian tube, or primary peritoneal cancer * Prior radiotherapy for localized cancer of the breast, head and neck, or skin allowed provided it was completed \> 3 years ago, and the patient remains free of recurrent or metastatic disease * No concurrent coumadin-type anticoagulants, including warfarin, at doses \> 1 mg/day * Concurrent low molecular weight heparin or low dose warfarin (i.e., ≤ 1 mg daily) for prophylaxis against central venous catheter thrombosis is allowed * No other concurrent investigational or antineoplastic agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0 | CT scan or MRI every other cycle for the first 6 months; then every 3 months thereafter; and at any other time if clinically indicated up to 5 years. | RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. 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. |
| Progression-free Survival (PFS) at 6 Months | CT scan or MRI every other cycle for the first 6 months | Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. In this study, time of progression could not be validly collected due to the study being prematurely closed secondary to severe neurological adverse events seen in 4 patients, |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Overall Survival (OS) | 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. | Overall survival is defined as the duration of time from study entry to time of death or the date of last contact. |
| Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Assessed every cycle while on treatment, 30 days after the last cycle of treatment | Number of participants with a maximum grade of 3 or higher during the treatment period. |
| Duration of Progression-free Survival (PFS) | CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months; then every 3 months thereafter; and at any other time if clinically indicated, up to 5 years | Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. In this study time of progression could not be validly collected due to the study being prematurely closed, secondary to severe neurological adverse events seen in 4 patients, and thus progression-free survival (PFS) cannot be presented. For safety reasons, most patients (16/22) were taken off study drug prior to progression (or AE), |
Countries
United States
Participant flow
Recruitment details
The study was activated on 12/10/2007 and closed to accrual on 4/22/2008.
Participants by arm
| Arm | Count |
|---|---|
| AMG 706 AMG 706 125 mg PO daily continuously (one cycle is 28 days) until disease progression or adverse effects prohibit further therapy | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible - improper prior treatment | 1 |
Baseline characteristics
| Characteristic | AMG 706 |
|---|---|
| Age, Continuous | 64.4 years STANDARD_DEVIATION 9.6 |
| Age, Customized Age at study entry 50-59 years | 7 Participants |
| Age, Customized Age at study entry 60-69 years | 9 Participants |
| Age, Customized Age at study entry 70-79 years | 5 Participants |
| Age, Customized Age at study entry 80-89 years | 1 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 22 |
| serious Total, serious adverse events | 11 / 22 |
Outcome results
Primary
Number of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0
RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. 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 every other cycle for the first 6 months; then every 3 months thereafter; and at any other time if clinically indicated up to 5 years.
Population: Eligible and treated patients.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AMG 706 | Number of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0 | Partial response | 1 Participants |
| AMG 706 | Number of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0 | Complete response | 0 Participants |
Primary
Progression-free Survival (PFS) at 6 Months
Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. In this study, time of progression could not be validly collected due to the study being prematurely closed secondary to severe neurological adverse events seen in 4 patients,
Time frame: CT scan or MRI every other cycle for the first 6 months
Population: Time of progression could not be validly collected due to the study being prematurely closed due to severe neurological adverse events, thus 6-month PFS cannot be presented. For safety reasons, most patients (16/22) were taken off study drug prior to progression (or AE), and follow-up for progression after coming off study was not collected.
Secondary
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.
Population: Eligible and treated patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AMG 706 | Duration of Overall Survival (OS) | 13.1 months |
Secondary
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 is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. In this study time of progression could not be validly collected due to the study being prematurely closed, secondary to severe neurological adverse events seen in 4 patients, and thus progression-free survival (PFS) cannot be presented. For safety reasons, most patients (16/22) were taken off study drug prior to progression (or AE),
Time frame: CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months; then every 3 months thereafter; and at any other time if clinically indicated, up to 5 years
Population: Study Analysis aborted due to severe toxicities. Estimates not calculated. Follow up for progression after coming off study was not collected in a manner that yields time to time to progression data.
Secondary
Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
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
Population: Eligible and treated patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AMG 706 | Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Gastrointestinal | 5 Participants |
| AMG 706 | Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Hepatobiliary | 1 Participants |
| AMG 706 | Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Metabolic | 4 Participants |
| AMG 706 | Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Muskuloskeletal | 1 Participants |
| AMG 706 | Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Pulmonary | 1 Participants |
| AMG 706 | Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Cardiac | 2 Participants |
| AMG 706 | Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Other Neurological | 4 Participants |
| AMG 706 | Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Pain | 1 Participants |
| AMG 706 | Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Death, Not CTC coded | 1 Participants |