Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Carcinoma
Conditions
Keywords
antibody therapy, chemotherapy, biologic therapy, combination therapy
Brief summary
The purpose of the study is to evaluate the efficacy and toxicity of irinotecan in the treatment of women with recurrent epithelial ovarian cancer or primary peritoneal cancer when combined with bevacizumab.
Detailed description
Accumulating data suggests that angiogenesis plays a critical role in the formation and development of a number of solid tumors including ovarian cancer. For women with ovarian cancer, a direct relationship between vascular endothelial growth factor (VEGF) expression and tumor vascularity has been documented. In vivo and in vitro data has demonstrated that increased angiogenesis and microvessel density are negative prognostic factors for women with ovarian cancer. These observations have fueled interest in incorporating anti-angiogenic agents into ovarian cancer treatment regimens. Several phase II trials of irinotecan in patients with epithelial ovarian cancer showed that the drug had efficacy in both chemotherapy-naïve patients and in those who had been previously treated with standard therapies, including platinum-based compounds, radiation, or both. Combination of bevacizumab, an antibody against VEGF, and irinotecan was studied in colorectal cancer and malignant brain neoplasms. In these trials, the combination was shown to be safe and effective. The purpose of this study is to evaluate the efficacy and toxicity of irinotecan in the treatment of women with recurrent epithelial ovarian cancer or primary peritoneal cancer when combined with bevacizumab. In this phase II open-label study patients will be treated with bevacizumab 15 mg/kg and irinotecan 175mg/m\^2 every 3 weeks. Patients will undergo pre-treatment evaluation within 4 weeks of enrolling into the study. Clinical and laboratory evaluation will be performed every 3 weeks. Imaging studies and CA-125 measurements will be used to assess response to treatment.
Interventions
DRUGIrinotecan
DRUGBevacizumab
Sponsors
Genentech, Inc.
NYU Langone Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women with recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal carcinoma * Patient should have measurable or evaluable disease as defined by the following. * Measurable disease: At least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be ≥ 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT and MRI, or ≥ 10 mm when measured by spiral CT. * Evaluable (nonmeasurable) disease: Patients who do not meet measurable criteria will be eligible having known disease with CA125 levels \>50 U/mL on two occasions at least one week apart. They will be considered for CA125 response criteria. * Any number of prior chemotherapy regimens * Any number of prior bevacizumab-containing regimens * No chemotherapy within the last 2 weeks prior to initiating this study. * Karnofsky Performance status score ≥ 60%. * Patients must have a life expectancy ≥ 12 weeks. * Patients must be at least 18 years of age. * Patients must understand and willingly sign an approved informed consent.
Exclusion criteria
* Inability to comply with study and/or follow-up procedures * Life expectancy of less than 12 weeks * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study * Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last five years Bevacizumab-Specific Exclusions * Inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg) * Prior history of hypertensive crisis or hypertensive encephalopathy * New York Heart Association (NYHA) Grade II or greater congestive heart failure * History of myocardial infarction or unstable angina within 6 months prior to Day 1 * History of stroke or transient ischemic attack within 6 months prior to Day 1 Known central nervous system disease, except for treated brain metastasis * Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded * Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 * History of hemoptysis (\>= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1 * Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study * Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1 * History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1 * Serious, non-healing wound, active ulcer, or untreated bone fracture * Proteinuria as demonstrated by a UPC ratio \>= 1.0 * Known hypersensitivity to any component of bevacizumab * Pregnancy (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in subjects of child-bearing potential * History of abdominal fistula or intra-abdominal abscess within 6 months prior to start. * Any history of prior gastrointestinal perforation * Patients believed to possibly be at higher than average risk of perforation, including symptoms or findings of partial or complete bowel obstruction, history of fistula, patients requiring parenteral nutrition and hydration, and those with history of prior perforation due to tumor or perforation within last 6 months from other causes will be excluded from study * Patients with evidence of abdominal free air not explained by paracentesis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Rate at 6 Months | 6 months from the start of treatment | The PFS rate at 6 months is the percentage of patients that experience a PFS event during the first 6 months in the study. The PFS is defined as the time from date of first dose of study medication to the date of first documented disease progression, or death from any cause, whichever is first. Patients who die without a reported prior progression will be considered to have progressed on the day of their death. Progression is evaluated by Response and Evaluation Criteria in Solid Tumor (RECIST) 1.0 or CA125 criteria if no measurable disease as doubling of CA125 levels from either the upper limit of normal or the nadir CA125 level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | up to 3 years | ORR is defined as the percentage of all patients with confirmed partial response (PR) or complete response (CR). PR and CR are evaluated by RECIST 1.0 or CA125 if no measurable disease (PR: CA125 decreases by \> 50%; CR: CA125 decreases to the normal range). |
| Median Progression Free Survival | up to 3 years | Defined as the length of time from the start of treatment that half of the patients are still alive and without disease progression. Progression is evaluated by RECIST 1.0 or CA125 if no measurable disease (PR: CA125 decreases by \> 50%; CR: CA125 decreases to the normal range; progression is defined on the basis of a confirmed doubling of CA125 levels from either the upper limit of normal or the nadir CA125 level) |
| Median Overall Survival | up to 3 years | Defined as the length of time from the start of treatment that half of the patients are still alive. |
| Number of Patients Who Experienced Grade 3 and Higher Toxicities | up to 3 years | — |
Countries
United States
Participant flow
Recruitment details
From April 2010 to May 2013, 29 patients were enrolled from New York University Langone Medical Center.
Participants by arm
| Arm | Count |
|---|---|
| Irinotecan With Bevacizumab Irinotecan is administered every 3 weeks at a dose of 175 mg/m\^2, bevacizumab is administered at 15 mg/kg every 3 weeks. Irinotecan is administered before bevacizumab. Patients will continue on therapy until evidence of disease progression, or until development of adverse events that prevent further treatment, or if the patients wishes to discontinue therapy.
Irinotecan
Bevacizumab | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Lack of Efficacy | 2 |
Baseline characteristics
| Characteristic | Irinotecan With Bevacizumab |
|---|---|
| Age, Continuous | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Number of prior regimens | 5 Regimens |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 29 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 | 29 / 29 |
| serious Total, serious adverse events | 9 / 29 |
Outcome results
Primary
Progression Free Survival (PFS) Rate at 6 Months
The PFS rate at 6 months is the percentage of patients that experience a PFS event during the first 6 months in the study. The PFS is defined as the time from date of first dose of study medication to the date of first documented disease progression, or death from any cause, whichever is first. Patients who die without a reported prior progression will be considered to have progressed on the day of their death. Progression is evaluated by Response and Evaluation Criteria in Solid Tumor (RECIST) 1.0 or CA125 criteria if no measurable disease as doubling of CA125 levels from either the upper limit of normal or the nadir CA125 level.
Time frame: 6 months from the start of treatment
Population: Intent-to-treat population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Irinotecan With Bevacizumab | Progression Free Survival (PFS) Rate at 6 Months | 55.2 percentage of patients |
Secondary
Median Overall Survival
Defined as the length of time from the start of treatment that half of the patients are still alive.
Time frame: up to 3 years
Population: Intent-to-treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Irinotecan With Bevacizumab | Median Overall Survival | 15.4 months |
Secondary
Median Progression Free Survival
Defined as the length of time from the start of treatment that half of the patients are still alive and without disease progression. Progression is evaluated by RECIST 1.0 or CA125 if no measurable disease (PR: CA125 decreases by \> 50%; CR: CA125 decreases to the normal range; progression is defined on the basis of a confirmed doubling of CA125 levels from either the upper limit of normal or the nadir CA125 level)
Time frame: up to 3 years
Population: Intent-to-treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Irinotecan With Bevacizumab | Median Progression Free Survival | 6.8 months |
Secondary
Number of Patients Who Experienced Grade 3 and Higher Toxicities
Time frame: up to 3 years
Population: Any patients who had at least one dose of treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Irinotecan With Bevacizumab | Number of Patients Who Experienced Grade 3 and Higher Toxicities | Diarrhea | 5 participants |
| Irinotecan With Bevacizumab | Number of Patients Who Experienced Grade 3 and Higher Toxicities | Fatigue | 3 participants |
| Irinotecan With Bevacizumab | Number of Patients Who Experienced Grade 3 and Higher Toxicities | Pain | 3 participants |
| Irinotecan With Bevacizumab | Number of Patients Who Experienced Grade 3 and Higher Toxicities | Hypertension | 2 participants |
| Irinotecan With Bevacizumab | Number of Patients Who Experienced Grade 3 and Higher Toxicities | Nausea | 2 participants |
| Irinotecan With Bevacizumab | Number of Patients Who Experienced Grade 3 and Higher Toxicities | Proteinuria | 2 participants |
| Irinotecan With Bevacizumab | Number of Patients Who Experienced Grade 3 and Higher Toxicities | Vomiting | 2 participants |
| Irinotecan With Bevacizumab | Number of Patients Who Experienced Grade 3 and Higher Toxicities | Febrile neutropenia | 1 participants |
| Irinotecan With Bevacizumab | Number of Patients Who Experienced Grade 3 and Higher Toxicities | GI obstruction: colon | 1 participants |
| Irinotecan With Bevacizumab | Number of Patients Who Experienced Grade 3 and Higher Toxicities | GI perforation | 1 participants |
| Irinotecan With Bevacizumab | Number of Patients Who Experienced Grade 3 and Higher Toxicities | Leukopenia | 1 participants |
Secondary
Overall Response Rate (ORR)
ORR is defined as the percentage of all patients with confirmed partial response (PR) or complete response (CR). PR and CR are evaluated by RECIST 1.0 or CA125 if no measurable disease (PR: CA125 decreases by \> 50%; CR: CA125 decreases to the normal range).
Time frame: up to 3 years
Population: Intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Irinotecan With Bevacizumab | Overall Response Rate (ORR) | 27.6 percentage of patients |