Platine, Avastin and OLAparib in 1st Line (PAOLA-1)
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|ClinicalTrials.gov Identifier: NCT02477644|
Recruitment Status : Active, not recruiting
First Posted : June 23, 2015
Last Update Posted : January 21, 2020
|First Submitted Date ICMJE||June 18, 2015|
|First Posted Date ICMJE||June 23, 2015|
|Last Update Posted Date||January 21, 2020|
|Actual Study Start Date ICMJE||May 6, 2015|
|Actual Primary Completion Date||March 22, 2019 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Efficacy by progression free survival (PFS1) [ Time Frame: phase up to a total of 15 months ]|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT02477644 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Platine, Avastin and OLAparib in 1st Line|
|Official Title ICMJE||Randomized, Double-Blind, Phase III Trial Olaparib vs. Placebo Patients With Advanced FIGO Stage IIIB-IV High Grade Serious or Endometrioid Ovarian, Fallopian Tube, or Peritoneal Cancer Treated Standard First-Line Treatment|
|Brief Summary||Randomized, Double-Blind, Phase III Trial of Olaparib vs. Placebo in Patients with Advanced FIGO Stage IIIB - IV High Grade Serous or Endometrioid Ovarian, Fallopian Tube, or Peritoneal Cancer treated with standard First-Line Treatment, Combining Platinum-Taxane Chemotherapy and Bevacizumab Concurrent with Chemotherapy and in Maintenance.|
|Detailed Description||Patients with advanced FIGO stage IIIB - IV high grade serous or endometrioid ovarian, fallopian tube, or peritoneal cancer treated with standard first-line treatment, combining platinum-taxane chemotherapy and bevacizumab concurrent with chemotherapy and in maintenance.|
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
|Condition ICMJE||Ovarian Cancer|
|Study Arms ICMJE||
|Publications *||Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, Fujiwara K, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alía EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marmé F, Combe P, de Gregorio N, Rodrigues M, Buderath P, Dubot C, Burges A, You B, Pujade-Lauraine E, Harter P; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2416-2428. doi: 10.1056/NEJMoa1911361.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Active, not recruiting|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Estimated Study Completion Date ICMJE||June 2022|
|Actual Primary Completion Date||March 22, 2019 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
I-1. Female Patient must be ≥18 years of age. I-2. Signed informed consent and ability to comply with treatment and follow-up.
I-3. Patient with newly diagnosed I-3-1 Ovarian cancer, primary peritoneal cancer and/or fallopian-tube cancer,
I-3-2 Histologically confirmed (based on local histopathological findings):
I-4. Patient who has completed prior to randomization first line platinum-taxane chemotherapy:
I-5. Patient must have received prior to randomization a minimum of 3 cycles of bevacizumab in combination with the 3 last cycles of platinum-based chemotherapy. Only in case of interval debulking surgery, it is allowed to realize only 2 cycles of bevacizumab in combination with the last 3 cycles of platinium-based chemotherapy. Bevacizumab treatment should be administered at a dose 15mg/kg q3 weeks up to a total of 15 months.
I-6. Patient must be prior to randomization without evidence of disease (NED) or in complete response (CR) or partial response (PR) from her first line treatment. There should be no clinical evidence of disease progression (physical exam, imagery, CA 125) throughout her first line treatment and prior to study randomization.
I-7. Patient must be randomized at least 3 weeks and no more than 9 weeks after her last dose of chemotherapy (last dose is the day of the last infusion) and all major toxicities from the previous chemotherapy must have resolved to CTC AE grade 1 or better (except alopecia and peripheral neuropathy).
I-8. Patient must have normal organ and bone marrow function:
I-9. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. I-10. Formalin fixed, paraffin embedded (FFPE) tumor sample from the primary cancer must be available for central BRCA testing and test result must be available for stratification.
I-11. Postmenopausal or evidence of non-childbearing status for women of childbearing potential prior to the first dose of study treatment. (see appendix 4) I-12. For France only: In France, a subject will be eligible for randomization in this study only if either affiliated to, or a beneficiary of, a social security category.
E-1. Non-epithelial origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors).
E-2. Ovarian tumors of low malignant potential (e.g. borderline tumors), or mucinous carcinoma.
E-3. Patient with synchronous primary endometrial cancer unless both of the following criteria are met:
Patient with serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium is not eligible.
E-4. Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS). Patient with a history of localized malignancy diagnosed over 5 years ago may be eligible provided she completed her adjuvant systemic therapy prior to randomization and that the patient remains free of recurrent or metastatic disease.
Patient with history of primary triple negative breast cancer may be eligible provided she completed her definitive anticancer treatment more than 3 years ago and she remains breast cancer disease free prior to start of study treatment.
E-5. Patient with myelodysplastic syndrome/acute myeloid leukemia history E-6. Patient having experienced for at least one cycle, a delay > 2 weeks due to prolonged hematological recovery during the first line chemotherapy E-7. Patient receiving radiotherapy within 6 weeks prior to study treatment E-8. Major surgery within 4 weeks of starting study treatment and patient must have recovered from any effects of any major surgery E-9. Previous allergenic bone marrow transplant. E-10. Any previous treatment with PARP inhibitor, including olaparib. E-11. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy is permitted as are steroidal antiemetics).
E-12. Current or recent (within 10 days prior to randomization) chronic use of aspirin > 325 mg/day.
E-13. Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
E-14. Prior history of hypertensive crisis (CTC-AE grade 4) or hypertensive encephalopathy.
E-15. Clinically significant (e.g. active) cardiovascular disease, including:
E-16. Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub- Arachnoids Hemorrhage (SAH) within 6 months prior to randomization.
E-17. History or evidence of hemorrhagic disorders within 6 months prior to randomization.
E-18. Evidence of bleeding diathesis or significant coagulopathy (in the absence of coagulation).
E-19. History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of suspected spinal cord compression.
E-20. History or evidence upon neurological examination of central nervous system (CNS) disease, unless adequately treated with standard medical therapy (e.g. uncontrolled seizures).
E-21. Significant traumatic injury during 4 weeks prior to randomization. E-22. Non-healing wound, active ulcer or bone fracture. Patient with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection is eligible but require 3 weekly wound examinations.
E-23. History of VEGF therapy related abdominal fistula or gastrointestinal perforation or active gastrointestinal bleeding within 6 months prior to the first study treatment.
E-24. Current, clinically relevant bowel obstruction, including sub-occlusive disease, related to underlying disease.
E-25. Patient with evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
E-26. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment related complications.
E-27. Pregnant or lactating women. E-28. Participation in another clinical study with an investigational product during her chemotherapy course immediately prior to randomization.
E-29. Patient unable to swallow orally administered medication and patient with gastrointestinal disorders likely to interfere with absorption of the study medication.
E-30. Patient with a known hypersensitivity to olaparib or any of the recipients of the product.
E-31. Immunocompromised patient, e.g., with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids or patient who is known to be serologically positive for human immunodeficiency virus (HIV).
|Ages ICMJE||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Austria, Belgium, Denmark, Finland, France, Germany, Italy, Japan, Monaco, Spain, Sweden|
|Removed Location Countries|
|NCT Number ICMJE||NCT02477644|
|Other Study ID Numbers ICMJE||GINECO-OV125b|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Arcagy Research|
|Study Sponsor ICMJE||Arcagy Research|
|PRS Account||Arcagy Research|
|Verification Date||January 2020|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP