The EndoBARR Trial (Endometrial Bevacizumab, Atezolizumab, Rucaparib)
Sponsor:
Medical College of Wisconsin
Collaborators:
Information provided by (Responsible Party):
William Bradley，Medical College of Wisconsin
| Tracking Information | |||
|---|---|---|---|
| First Submitted Date ICMJE | September 26, 2018 | ||
| First Posted Date ICMJE | October 3, 2018 | ||
| Last Update Posted Date | October 3, 2018 | ||
| Actual Study Start Date ICMJE | February 1, 2019 | ||
| Estimated Primary Completion Date | February 28, 2021 (Final data collection date for primary outcome measure) | ||
| Current Primary Outcome Measures ICMJE |
Overall Response Rate[ Time Frame: 30-36 months ] To estimate the overall response rate (ORR) of patients with progressive/persistent or recurrent endometrial cancer on study-directed therapy, using the combination of rucaparib, bevacizumab and atezolizumab. |
||
| Original Primary Outcome Measures ICMJE | Same as current | ||
| Current Secondary Outcome Measures ICMJE |
|
||
| Descriptive Information | |||
| Brief Title ICMJE | The EndoBARR Trial (Endometrial Bevacizumab, Atezolizumab, Rucaparib) |
||
| Official Title ICMJE | An Open Label, Non-Randomized Multisite Phase II Trial Combining Bevacizumab, Atezolizumab and Rucaparib for the Treatment of Previously Treated Recurrent and Progressive Endometrial Carcinoma |
||
| Brief Summary | To demonstrate the efficacy and safety of the combination of rucaparib, bevacizumab and atezolizumab in recurrent, progressive endometrial carcinoma. |
||
| Detailed Description | The combination of the three proposed agents offers the opportunity to explore synergistic relationships between antiangiogenic and immunotherapy and antiangiogenic and PARPi. Increasing genetic instability by PARPi and double-strand breaks may lead to a proinflammatory state that would enhance the activity of immunotherapy, leading to synergistic response in a category of solid tumors that lack active therapy. It is expected that increased double-strand breaks may lead to increased expression of immunogenic antigens, increasing the effect of anti-PD-L1 therapy. Phase I data combining the PD-L1 inhibitor durvalamab with either olaparib or cediranib showed good tolerability and evidence of response. | ||
| Study Type ICMJE | Interventional | ||
| Study Phase | Phase 2 | ||
| Study Design ICMJE | Allocation: Intervention Model: Single Group Assignment Intervention Model Description: Cycle length = 21 days Atezolizumab 1,200mg IV on day 1 Bevacizumab 15mg/kg IV on day 1 Rucaparib 600mg orally twice daily by continuous dosing Masking: Interventional Masking Description: Primary Purpose: Treatment |
||
| Condition ICMJE | |||
| Intervention ICMJE |
|
||
| Study Arms |
|
||
| Recruitment Information | |||
| Recruitment Status ICMJE | Not yet recruiting | ||
| Estimated Enrollment ICMJE |
30 | ||
| Original Estimated Enrollment ICMJE | Same as current | ||
| Estimated Study Completion Date | February 28, 2026 | ||
| Estimated Primary Completion Date | February 28, 2021 (Final data collection date for primary outcome measure) | ||
| Eligibility Criteria ICMJE | Inclusion Criteria: 1. Patients must have recurrent or persistent/progressive endometrial carcinoma, which is refractory to curative therapy or established treatments. Histologic confirmation of the original primary tumor is required. Stained slides to document the either the primary or recurrent tumor are required. If primary FFPE samples are not available, a biopsy demonstrating recurrent disease must be obtained. Pathologic Slides/Blocks will be reviewed at the primary site for confirmation. 2. Patients with the following histologic epithelial cell types are eligible: Endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, transitional cell carcinoma and uterine carcinosarcoma (MMT). 3. Patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma. Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a chemotherapy regimen. Patients may have had, but are not required to have received, a second chemotherapeutic regimen for recurrent disease. 4. All patients must have measurable disease, as defined by RECIST 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each target lesion must be ≥ 10 mm when measured by CT or MRI. Lymph nodes must be > 15 mm in short axis when measured by CT or MRI. 5. Patients may be enrolled if they do not have a target lesion (>= 10 mm lesion or >=15 mm lymph node), if they have measurable disease. This is defined by RECIST 1.1 as a suspicicious lesion <10mm or a lymph node >=10mm but <15mm. 6. Patients must have an EGOG Performance Status of 0, 1. 7. Recovery from effects of recent surgery, radiotherapy, or chemotherapy 8. Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated UTI). 9. Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration. 10. Any other prior therapy directed at the malignant tumor, including chemotherapy and immunologic agents, must be discontinued at least three weeks prior to first cycle of treatment. 11. Any prior radiation therapy must be completed at least four weeks prior to first cycle of treatment. 12. Prior hormonal therapy is allowed. There is no limit on the number of prior hormonal therapies allowed. Hormonal therapy will not be counted as a line of therapy for purposes of this trial. 13. Patients must have a urine protein of 2+ on dipstick. If dipstick is >2+, 24-hour urine protein must be obtained and should be < 1g for patient to be eligible. 14. Patients must have signed an approved informed consent and authorization permitting release of personal health information. 15. Patients must meet pre-entry requirements, as specified in section 5. 16. Patients of childbearing potential must agree to use an accepted and effective nonhormonal method of contraception i.e., double-barrier method (e.g., condom plus diaphragm) from the time of signing the informed consent through six months after last dose of study drug. 17. Patients 18 years of age or greater. 18. Be willing to provide tissue from the primary surgical resection (paraffin block). 19. Must have adequate organ function for screening labs. Exclusion Criteria: 1. Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last two years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy. 2. Patients must not have had exposure to Bevacizumab, PARPi, or immunotherapy. Patients may have had exposure to anti-angiogentic therapy provided it was not Bevacizumab. 3. Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last three years are excluded. Prior radiation for localized cancer of the breast, head and neck or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease. 4. Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of endometrial cancer within the last three years are excluded. Patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than two years prior to registration, and that the patient remains free of recurrent or metastatic disease. 5. Inability to tolerate an oral medication or keep pills down. 6. Patients who are pregnant or nursing. 7. Patients with a complete bowel obstruction; recent (within six months) history of fistula, intraabdominal abscess or bowel perforation; subjects requiring total parenteral nutrition or parenteral hydration. 8. Has a current diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within seven days prior to the first dose of trial treatment. 9. Patients with history or evidence upon physical examination of CNS disease, including brain tumor, seizures not controlled with standard medical therapy or any brain metastases. 10. Patients with clinically significant cardiovascular disease. This includes: - Myocardial infarction or unstable angina within 12 months of the first date of study treatment. - New York Heart Association (NYHA) Class II or greater congestive heart failure (Appendix I). - History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication). - Grade 2 or greater peripheral vascular disease. - Cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of study treatment. - History of arterial ischemia or thrombus. 11 Patients with uncontrolled hypertension defined as systolic > 150 mm Hg or diastolic > 90 mm Hg. The use of antihypertensive medications to control hypertension is permitted. 12 Patients who have undergone major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of study treatment or who have a major surgical procedure anticipated during the course of the study. Laparoscopic biopsy is acceptable and will not require a delay in study treatment. 13 Patients with serious nonhealing wound, ulcer (including gastrointestinal) or bone fracture. 14 Patients with any condition, which in the investigator's opinion, makes the patient unsuitable for study participation. 15 Patients not available for follow-up assessments. 16 Patients with known sensitivity to any of the products to be administered during dosing. | ||
| Sex/Gender |
|
||
| Ages | 18 Years and older (Adult, Older Adult) | ||
| Accepts Healthy Volunteers | No | ||
| Listed Location Countries ICMJE | United States | ||
| Removed Location Countries | |||
| Administrative Information | Has Data Monitoring Committee | Yes | |
| U.S. FDA-regulated Product |
Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No |
||
| IPD Sharing Statement |
|
||
| Responsible Party | William Bradley，Medical College of Wisconsin | ||
| Study Sponsor ICMJE | Medical College of Wisconsin | ||
| Collaborators ICMJE | |||
| Investigators ICMJE |
|
||
| PRS Account | Medical College of Wisconsin | ||
| Verification Date | September 2018 | ||
|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
|||
请使用微信扫码报名
京公网安备 11010102003638号