Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cancer
Conditions
Keywords
Sutent, sunitinib
Brief summary
The purpose of this study is to determine the effectiveness of sunitinib on participants with ovarian, fallopian tube or peritoneal cancer. Sunitinib is a newly discovered drug that may stop cancer cells from growing by blocking the blood supply to the tumor.
Detailed description
This study used a two-stage design to evaluate efficacy of sunitinib based on overall response (OR) defined as complete response (CR) or partial response (PR). The null and alternative OR rate were 5% and 20%. If one or more patients enrolled in the stage one cohort (n=17 patients) achieved PR or better than accrual would proceed to stage two (n=18 patients). There was 42% probability of stopping the trial at stage one if the true OR rate was 5%. With 35 patients, this design had 85% power to detect the 15% difference in OR rates assuming 2-sided type I error rate of 0.05.
Interventions
DRUGSunitinib
Sponsors
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Massachusetts General Hospital
Dana-Farber Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed epithelial ovarian, fallopian tube or peritoneal cancer * Recurrent or refractory disease * Measurable disease, defined by RECIST * 0 to 3 prior cytotoxic chemotherapy or biologic regimens for metastatic disease * Adverse events related to prior tumor-specific therapy must have resolved to less than or equal to grade 1 prior to study entry * Ability to swallow oral medications * 18 years of age or older * ECOG Performance status must be 0-2 * Normal organ and marrow function as outlined in the protocol
Exclusion criteria
* Receiving systemic therapy less than 14 days prior to starting sunitinib * Receiving any other investigational agent * Received prior sunitinib * Untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on screening CT or MRI scans * Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism. * Evidence of a bleeding diathesis. Major surgery or NCI CTCA 3.0 grade 3 or worse hemorrhage within 4 weeks of starting study treatment * Ongoing cardiac dysrhythmias of NCI CTCAE version 3.0 grade \> 2 * Pre-existing thyroid abnormality, with thyroid function tests that cannot be maintained in the normal range with medication * Prolonged QTc interval on baseline EKG * Uncontrolled hypertension * Patients who are taking cytochrome P450 enzyme-inducing antiepileptic drugs, rifampin, theophylline, ketoconazole, or St. John's wort. * Psychiatric illness or social situations that wold limit compliance with study requirements * Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration * Pregnant women * Clinical or radiographical evidence of a small bowel obstruction * Poor oral intake
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | Clinical assessments were performed weekly for first 4 weeks and every 2 wks in subsequent cycles. Disease was evaluated radiologically at baseline, before each odd cycle and at end of trt. | Best response on treatment was based on RECIST 1.0 criteria with overall response defined as achieving partial response (PR) or complete response (CR). Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 16-Week Progression-Free Survival | Clinical assessments were performed weekly for first 4 weeks and every 2 weeks in subsequent cycles. Disease was evaluated radiologically at baseline, before each odd cycle and at end of treatment. | 16-week progression-free survival is the probability of patients remaining alive and progression-free at 16-weeks from study entry estimated using Kaplan-Meier methods. Patients alive and progression-free at last follow-up are censored. Progressive disease (PD) based on RECIST 1.0 is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or equivocal progression of non-target lesions. |
| Progression-Free Survival | Clinical assessments were performed weekly for first 4 weeks and every 2 weeks in subsequent cycles. Disease was evaluated radiologically at baseline, before each odd cycle and at end of treatment. | Progression-free survival estimated using Kaplan-Meier methods is defined as the time from registration to the earlier of death or disease progression. Patients alive without disease progression are censored at the date of last disease evaluation. Progressive disease (PD) based on RECIST 1.0 is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Equivocal progression of non-target lesions also qualifies as PD. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the GYN Oncology clinics at the DFCI, MGH and BIDMC. Thirty six consenting participants were enrolled over a 19 month period.
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib Patients received oral Sunitinib at the daily dose of 37.5 mg continuously over a 28- day treatment cycle. Treatment continued until clinical or radiological evidence of progressive disease or excessive toxicity. | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 13 |
| Overall Study | Patient or MD Decision to End Treatment | 1 |
| Overall Study | Progressive Disease | 21 |
| Overall Study | Pt Withdrew Consent | 1 |
Baseline characteristics
| Characteristic | Sunitinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants |
| Age, Continuous | 61 years STANDARD_DEVIATION 8.8 |
| Histology Clear cell | 5 participants |
| Histology Endometrioid | 2 participants |
| Histology Mixed Mullerian tumor | 3 participants |
| Histology Other (adenocarcinoma/mixed histology) | 3 participants |
| Histology Papillary serous | 23 participants |
| Region of Enrollment United States | 36 participants |
| Sex: Female, Male Female | 36 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 | 36 / 36 |
| serious Total, serious adverse events | 7 / 36 |
Outcome results
Primary
Overall Response Rate
Best response on treatment was based on RECIST 1.0 criteria with overall response defined as achieving partial response (PR) or complete response (CR). Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Time frame: Clinical assessments were performed weekly for first 4 weeks and every 2 wks in subsequent cycles. Disease was evaluated radiologically at baseline, before each odd cycle and at end of trt.
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib | Overall Response Rate | .083 proportion of participants |
Secondary
16-Week Progression-Free Survival
16-week progression-free survival is the probability of patients remaining alive and progression-free at 16-weeks from study entry estimated using Kaplan-Meier methods. Patients alive and progression-free at last follow-up are censored. Progressive disease (PD) based on RECIST 1.0 is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or equivocal progression of non-target lesions.
Time frame: Clinical assessments were performed weekly for first 4 weeks and every 2 weeks in subsequent cycles. Disease was evaluated radiologically at baseline, before each odd cycle and at end of treatment.
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib | 16-Week Progression-Free Survival | .36 probability |
Secondary
Progression-Free Survival
Progression-free survival estimated using Kaplan-Meier methods is defined as the time from registration to the earlier of death or disease progression. Patients alive without disease progression are censored at the date of last disease evaluation. Progressive disease (PD) based on RECIST 1.0 is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Equivocal progression of non-target lesions also qualifies as PD.
Time frame: Clinical assessments were performed weekly for first 4 weeks and every 2 weeks in subsequent cycles. Disease was evaluated radiologically at baseline, before each odd cycle and at end of treatment.
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | Progression-Free Survival | 9.9 weeks |