Fallopian Tube Cancer, Primary Peritoneal Serous Adenocarcinoma, Recurrent Ovarian Epithelial Cancer, Stage II Ovarian Epithelial Cancer, Stage I Ovarian Epithelial Cancer
Conditions
Brief summary
This phase II trial is studying how well AZD2171 works in treating patients with recurrent ovarian, peritoneal, or fallopian tube cancer. AZD2171 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
Detailed description
PRIMARY OBJECTIVES: I. To determine the efficacy of AZD2171 in platinum sensitive and platinum insensitive disease, based on either RECIST criteria (for patients with measurable cancer radiographically) or clinical response benefit (modified Gynecologic Cancer Intergroup \[GCIG\] CA-125 response or stable disease for at least 16 weeks). SECONDARY OBJECTIVES: I. To assess progression-free survival. II. To assess modified GCIG CA-125 response rate. III. To assess duration of modified GCIG CA-125 response. IV. To assess the safety of the recommended phase 2 dose of AZD2171 in this asymptomatic patient population. V. To explore the pharmacodynamic effects of AZD2171 by correlating clinical outcomes with an angiogenic profile derived from serial assessments of soluble VEGFR2, circulating endothelial cell levels, and VEGFR phosphorylation in circulating endothelial cells. VI. To explore pharmacogenetic differences in kdr/flk-1, HIF1alpha, p53, and endothelial nitric oxide synthase (eNOS) in PBMCs from subjects who consent separately for pharmacogenetic studies. VII. To determine whether oncogenic mutations predict response to AZD2171. OUTLINE: This is a multicenter study. Patients are stratified according to disease sensitivity (platinum-sensitive disease vs platinum-insensitive disease). Patients receive oral AZD2171 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 periodically for up to 2 years. PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study.
Interventions
DRUGcediranib maleate
Given orally
Sponsors
National Cancer Institute (NCI)
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
* must have histologically or cytologically confirmed epithelial ovarian cancer, primary peritoneal serous cancer, or fallopian tube cancer * must have either measurable cancer by RECIST criteria or an elevated CA125 * Subjects must be asymptomatic or minimally symptomatic * Prior therapy: * Prior chemotherapy must have included a first-line platinum-based regimen only * Prior hormonal-based therapy for ovarian, primary peritoneal serous or fallopian tube cancer is acceptable * Up to two prior lines of chemotherapy in the recurrent setting are allowed * Toxic side effects related to prior chemotherapy or hormonal therapy must have resolved to less than or equal to grade 1 or to baseline (excluding alopecia), or for peripheral neuropathy to less than or equal to grade 2 * Subjects may begin AZD2171 at least 3 weeks after their last dose of chemotherapy or hormonal therapy * Life expectancy of greater than 6 months * ECOG performance status 0-1 (Karnofsky \>= 70%) * must have lab values within normal institutional limits * eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or PK of AZD2171 will be determined following review of their case by the Principal Investigator * Subjects with treated limited stage basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the breast or cervix are eligible; subjects with stage I or II cancer treated with a curative intent are also eligible with no evidence of recurrent disease * No evidence of preexisting uncontrolled hypertension; if patient has hypertension, it must be medically controlled * AZD2171 has been shown to terminate fetal development in the rat, as expected for a process dependent on VEGF signaling; for this reason, women of child-bearing potential must have a negative pregnancy test prior to study entry; must agree to use adequate contraception; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * Ability to understand and the willingness to sign a written informed consent document- No therapeutic anticoagulation; the use of low dose warfarin (1 mg/day), intermittent doses of tPA (2 mg x 1), or heparin flushes to prophylax against central venous catheter-associated clots is permitted * Measurable or non-measurable disease on CT scan or MRI * Consider patients who have the following risk factors to be at increased risk; these patients should have increased monitoring: * Prior treatment with anthracyclines * Prior treatment with trastuzumab * A New York Heart Association classification of II controlled with treatment * Prior central thoracic radiation therapy (RT), including RT to the heart * History of myocardial infarction within 12 months
Exclusion criteria
* Patients who have had chemotherapy, radiotherapy, or major surgery within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier * Patients may not be receiving any other investigational agents nor have participated in an investigational trial within the past 3 weeks; subjects may not have received prior treatment affecting the VEGF pathway; subjects may not have received prior treatment with antibodies that may interfere with CA-125 measurements; subjects may not have received intraperitoneal therapy within the 4 weeks prior to starting AZD2171 and/or the treating physician must confirm the patient has recurrent disease * Patients may not be receiving any medication that may markedly affect renal function * Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis * History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171 * Mean QTc \> 500 msec (with Bazett's correction) in screening electrocardiogram or history of familial long QT syndrome * Uncontrolled intercurrent illness * Pregnant women are excluded from this study because AZD2171 is a VEGF inhibitor with known abortifacient effects; breastfeeding should be discontinued if the mother is treated with AZD2171 * Major surgical procedure or medical interference with the peritoneum or pleura within 4 weeks of baseline CA-125 assessments * Subjects with a history of an active malignancy during the last 3 years except non-melanomatous skin cancer , in situ breast or cervical cancer or stage I or II cancer treated with a curative intent and no active cancer recurrence * HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD2171 * No therapeutic anti-coagulation; prophylaxis against central venous catheter-associated clots is permitted * A New York Heart Association classification of III or IV * Conditions requiring concurrent use of drugs or biologics with proarrhythmic potentiate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response Benefit (Modified Gynecologic Cancer InterGroup [GCIG] Cancer Antigen [CA]-125 Response or Stable Disease) Based on the Response Evaluation Criteria in Solid Tumors (RECIST) | Up to 12 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RESIST) Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the 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 Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free Survival | Up to 2 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Cediranib Maleate) Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
cediranib maleate: Given orally
laboratory biomarker analysis: Correlative studies
pharmacological study: Correlative studies | 46 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 9 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Progressive Disease | 30 |
| Overall Study | Withdrawal by Subject | 5 |
| Overall Study | Withdrew consent before treatment began | 1 |
Baseline characteristics
| Characteristic | Treatment (Cediranib Maleate) |
|---|---|
| Age, Continuous | 56.5 years |
| ECOG PS 0 | 34 participants |
| ECOG PS 1 | 12 participants |
| Histologic Subtype Clear cell | 3 participants |
| Histologic Subtype Endometrioid | 1 participants |
| Histologic Subtype Mixed type or other | 4 participants |
| Histologic Subtype Papillary serous | 38 participants |
| Number of Prior Therapies for Recurrent Cancer 0 | 19 participants |
| Number of Prior Therapies for Recurrent Cancer 1 | 22 participants |
| Number of Prior Therapies for Recurrent Cancer 2 | 5 participants |
| Platinum Sensitivity Platinum Resistant | 30 participants |
| Platinum Sensitivity Platinum Sensitive | 16 participants |
| Primary Cancer Diagnosis Fallopian tube cancer | 1 participants |
| Primary Cancer Diagnosis Ovarian cancer | 40 participants |
| Primary Cancer Diagnosis Peritoneal cancer | 5 participants |
| Prior History of Hypertension No | 40 participants |
| Prior History of Hypertension Yes | 6 participants |
| Race/Ethnicity, Customized Asian | 1 participants |
| Race/Ethnicity, Customized White (non-Hispanic) | 45 participants |
| Region of Enrollment United States | 46 participants |
| Response Assessment CA-125 | 10 participants |
| Response Assessment RECIST | 36 participants |
| Sex: Female, Male Female | 46 Participants |
| Sex: Female, Male Male | 0 Participants |
| Tumor grade 1 | 1 participants |
| Tumor grade 2 | 0 participants |
| Tumor grade 2-3 | 6 participants |
| Tumor grade 3 | 39 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 46 / 46 |
| serious Total, serious adverse events | 17 / 46 |
Outcome results
Primary
Clinical Response Benefit (Modified Gynecologic Cancer InterGroup [GCIG] Cancer Antigen [CA]-125 Response or Stable Disease) Based on the Response Evaluation Criteria in Solid Tumors (RECIST)
Per Response Evaluation Criteria In Solid Tumors Criteria (RESIST) Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the 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 Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
Time frame: Up to 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Cediranib Maleate) | Clinical Response Benefit (Modified Gynecologic Cancer InterGroup [GCIG] Cancer Antigen [CA]-125 Response or Stable Disease) Based on the Response Evaluation Criteria in Solid Tumors (RECIST) | Stable Disease | 6 participants |
| Treatment (Cediranib Maleate) | Clinical Response Benefit (Modified Gynecologic Cancer InterGroup [GCIG] Cancer Antigen [CA]-125 Response or Stable Disease) Based on the Response Evaluation Criteria in Solid Tumors (RECIST) | Complete Response | 0 participants |
| Treatment (Cediranib Maleate) | Clinical Response Benefit (Modified Gynecologic Cancer InterGroup [GCIG] Cancer Antigen [CA]-125 Response or Stable Disease) Based on the Response Evaluation Criteria in Solid Tumors (RECIST) | Partial Response | 8 participants |
| Treatment (Cediranib Maleate) | Clinical Response Benefit (Modified Gynecologic Cancer InterGroup [GCIG] Cancer Antigen [CA]-125 Response or Stable Disease) Based on the Response Evaluation Criteria in Solid Tumors (RECIST) | Progressive Disease | 21 participants |
Secondary
Progression-free Survival
Time frame: Up to 2 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Cediranib Maleate) | Progression-free Survival | 18.43 weeks | Standard Error 1.4278 |