OlympiA: Olaparib as Adjuvant Treatment in Patients With Germline BRCA Mutated High Risk HER2 Negative Primary Breast Cancer
Study Details
Study Description
Brief Summary
Olaparib treatment in patients with germline BRCA1/2 mutations and high risk HER2 negative primary breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
Detailed Description
Patients will be randomised in 1:1 ratio to either olaparib or placebo. Randomisation will be stratified by Hormone receptor status (ER and/or PgR positive/HER2 negative versus TNBC), prior neoadjuvant versus adjuvant chemotherapy and prior platinum use for breast cancer.
Randomised patients will receive study treatment for up to a maximum of 12 months. All patients will have safety assessments every 2 weeks during the first month, every 4 weeks for the following 5 months and 3 monthly for the remaining 6 months of study treatment plus 30 days after its discontinuation. Following randomisation, all patients will be assessed regularly for signs, symptoms and evidence of disease recurrence by taking medical history, physical examination and mammogram/breast MRI. Efficacy assessments will be performed on a 3 monthly basis during the first 2 years, followed by 6 monthly assessments for years 3, 4 and 5 and annually thereafter. All patients (except those with bilateral mastectomy) will have mammogram / breast MRI annually for 10 years beginning 6 months after randomisation.
All randomised patients will have clinical assessment visits for 10 years following their randomisation into the study. Once a patient completes 10 years of clinical assessment they will enter the survival follow up phase of the trial which will continue until 10 years after the last patient is randomised.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Olaparib Olaparib tablets 300mg b.i.d. p.o. |
Drug: Olaparib
Patients will be administred olaparib orally twice daily (b.i.d.) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 ml of water.
Other Names:
|
Placebo Comparator: Placebo Placebo tablets b.i.d. p.o. |
Drug: Placebo
Patients will be administred matching placebo. Two (2) tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 ml of water.
|
Outcome Measures
Primary Outcome Measures
- Invasive Disease Free Survival (IDFS) [From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months)]
An IDFS event is defined as the first occurrence of loco-regional or distant recurrence or new cancer or death from any cause.
Secondary Outcome Measures
- Distant Disease Free Survival (DDFS) [From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months)]
A DDFS event is defined as documented evidence of first distant recurrence of breast cancer or death from any cause
- Overall Survival (OS) [From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months)]
An OS event is defined as death by any cause.
- Number of Participants With Contralateral Breast Cancers, New Primary Ovarian Cancer, New Primary Fallopian Tube Cancer and New Primary Peritoneal Cancer [From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months)]
Number of patients with contralateral invasive breast cancer, contralateral non-invasive breast cancer, new primary ovarian cancer, new primary fallopian tube cancer and new primary peritoneal cancer. Analysis of contralateral breast cancers exclude patients with a bilateral mastectomy prior to randomisation. Analysis of new primary ovarian cancers excludes male patients and patients with a bilateral oophorectomy prior to randomisation. Analysis of new primary fallopian tube cancer excludes male patients and patients with a bilateral salpingectomy prior to randomisation. Analysis of new primary peritoneal cancers excludes male patients.
- Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Neoadjuvant Chemotherapy [6 and 12 months after randomisation]
Change from baseline for FACIT-Fatigue Score at 6 and 12 months for patients who completed neoadjuvant chemotherapy. Adjusted least-square mean changes and 95% Confidence Interval (CI) are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. FACIT-Fatigue score ranges from 0 to 52 with higher score indicating less fatigue.
- Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Adjuvant Chemotherapy [6 and 12 months after randomisation]
Change from baseline for FACIT-Fatigue Score at 6 and 12 months for patients who completed adjuvant chemotherapy. Adjusted least-square mean changes and 95% CI are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. FACIT-Fatigue score ranges from 0 to 52 with higher score indicating less fatigue.
- Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Neoadjuvant Chemotherapy [6 and 12 months after randomisation]
Change from baseline for EORTC QLQ-C30 Global health status QOL (Quality of Life) Score at 6 and 12 months for patients who completed neoadjuvant chemotherapy. Adjusted least-square mean changes and 95% CI are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. EORTC QLQ-C30 scores range from 0 to 100 with higher score indicating better quality of life.
- Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Adjuvant Chemotherapy [6 and 12 months after randomisation]
Change from baseline for EORTC QLQ-C30 Global health status QOL (Quality of Life) Score at 6 and 12 months for patients who completed adjuvant chemotherapy. Adjusted least-square mean changes and 95% CI are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. EORTC QLQ-C30 scores range from 0 to 100 with higher score indicating better quality of life.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast that is one of the following phenotypes:
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Triple negative breast cancer defined as: ER and PgR negative AND HER2 negative (not eligible for anti-HER2 therapy)
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ER and/or PgR positive, HER2 negative
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Documented germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function).
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Completed adequate breast and axilla surgery.
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Completed at least 6 cycles neoadjuvant or adjuvant chemotherapy containing anthracyclines, taxanes or the combination of both. Prior platinum as potentially curative treatment for prior cancer (e.g. ovarian) or as adjuvant or neoadjuvant treatment for breast cancer is allowed.
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ECOG 0-1.
Exclusion criteria:
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Any previous treatment with a PARP inhibitor, including olaparib and/or known hypersensitivity to any of the excipients of study treatment.
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Patients with second primary malignancy. EXCEPTIONS are:
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adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, Ductal Carcinoma in situ (DCIS) of the breast, stage 1 grade 1 endometrial carcinoma
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other solid tumours and lymphomas (without bone marrow involvement) diagnosed ≥ 5 years prior to randomisation and treated with no evidence of disease recurrence and for whom no more than one line of chemotherapy was applied.
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Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks. Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
-
Evidence of metastatic breast cancer
Contacts and Locations
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349 | Research Site | Green Bay | Wisconsin | United States | |
350 | Research Site | Kenosha | Wisconsin | United States | |
351 | Research Site | La Crosse | Wisconsin | United States | 54601 |
352 | Research Site | Ladysmith | Wisconsin | United States | 54848 |
353 | Research Site | Marinette | Wisconsin | United States | 54143 |
354 | Research Site | Marshfield | Wisconsin | United States | 54449 |
355 | Research Site | Menomonee Falls | Wisconsin | United States | |
356 | Research Site | Milwaukee | Wisconsin | United States | |
357 | Research Site | Minocqua | Wisconsin | United States | 54548 |
358 | Research Site | Mukwonago | Wisconsin | United States | |
359 | Research Site | Oconomowoc | Wisconsin | United States | |
360 | Research Site | Rice Lake | Wisconsin | United States | 54868 |
361 | Research Site | Stevens Point | Wisconsin | United States | 54482 |
362 | Research Site | Summit | Wisconsin | United States | |
363 | Research Site | Waukesha | Wisconsin | United States | |
364 | Research Site | Wausau | Wisconsin | United States | 54401 |
365 | Research Site | Wauwatosa | Wisconsin | United States | |
366 | Research Site | West Allis | Wisconsin | United States | |
367 | Research Site | Weston | Wisconsin | United States | 54476 |
368 | Research Site | Wisconsin Rapids | Wisconsin | United States | 54494 |
369 | Research Site | Berazategui | Argentina | B1884BBF | |
370 | Research Site | Caba | Argentina | C1426ANZ | |
371 | Research Site | Ciudad Autonoma De Buenos Aire | Argentina | C1125ABD | |
372 | Research Site | Cordoba | Argentina | 5000 | |
373 | Research Site | Cordoba | Argentina | X5002AOQ | |
374 | Research Site | La Rioja | Argentina | 5300 | |
375 | Research Site | Mendoza | Argentina | 5500 | |
376 | Research Site | Rosario | Argentina | S2000KZE | |
377 | Research Site | San Miguel de Tucuman | Argentina | T4000IAK | |
378 | Research Site | Santa Fe | Argentina | S3000FFU | |
379 | Research Site | Adelaide | Australia | 5000 | |
380 | Research Site | Auchenflower | Australia | 4066 | |
381 | Research Site | Concord | Australia | 2139 | |
382 | Research Site | Douglas | Australia | 4814 | |
383 | Research Site | Gosford | Australia | 2250 | |
384 | Research Site | Hobart | Australia | 7000 | |
385 | Research Site | Malvern | Australia | 3144 | |
386 | Research Site | Melbourne | Australia | 3000 | |
387 | Research Site | Nedlands | Australia | 6009 | |
388 | Research Site | Randwick | Australia | 2031 | |
389 | Research Site | South Brisbane | Australia | 4101 | |
390 | Research Site | Tamworth | Australia | 2340 | |
391 | Research Site | Tweed Heads | Australia | 2485 | |
392 | Research Site | Waratah | Australia | 2298 | |
393 | Research Site | Wendouree | Australia | 3355 | |
394 | Research Site | Graz | Austria | 8036 | |
395 | Research Site | Innsbruck | Austria | 6020 | |
396 | Research Site | Leoben | Austria | 8700 | |
397 | Research Site | Linz | Austria | 4010 | |
398 | Research Site | Linz | Austria | 4020 | |
399 | Research Site | Rankweil | Austria | 6830 | |
400 | Research Site | Ried | Austria | 4910 | |
401 | Research Site | Salzburg | Austria | 5020 | |
402 | Research Site | St. Veit an der Glan | Austria | 9300 | |
403 | Research Site | Vienna | Austria | 1130 | |
404 | Research Site | Vienna | Austria | 1160 | |
405 | Research Site | Villach | Austria | 9500 | |
406 | Research Site | Voecklabruck | Austria | 4840 | |
407 | Research Site | Weiz | Austria | 8160 | |
408 | Research Site | Wels | Austria | 4600 | |
409 | Research Site | Wien | Austria | 1090 | |
410 | Research Site | Wien | Austria | 1130 | |
411 | Research Site | Anderlecht | Belgium | 1070 | |
412 | Research Site | Brussels | Belgium | 1070 | |
413 | Research Site | Brussels | Belgium | 1090 | |
414 | Research Site | Bruxelles | Belgium | 1200 | |
415 | Research Site | Charleroi | Belgium | 6000 | |
416 | Research Site | Edegem | Belgium | 2650 | |
417 | Research Site | Kortrijk | Belgium | 8500 | |
418 | Research Site | Leuven | Belgium | 3000 | |
419 | Research Site | Liege | Belgium | 4000 | |
420 | Research Site | Namur | Belgium | 5000 | |
421 | Research Site | Oostende | Belgium | 8400 | |
422 | Research Site | Edmonton | Alberta | Canada | T6G 1Z2 |
423 | Research Site | Vancouver | British Columbia | Canada | V5Z 4E6 |
424 | Research Site | Winnipeg | Manitoba | Canada | R3E 0V9 |
425 | Research Site | Hamilton | Ontario | Canada | L8V 5C2 |
426 | Research Site | Toronto | Ontario | Canada | M4N 3M5 |
427 | Research Site | Greenfield Park | Quebec | Canada | J4V 2H1 |
428 | Research Site | Montreal | Quebec | Canada | H2W 1T8 |
429 | Research Site | Montreal | Quebec | Canada | H3T 1E2 |
430 | Research Site | Regina | Saskatchewan | Canada | S4T 7T1 |
431 | Research Site | Saskatoon | Saskatchewan | Canada | S7N 4H4 |
432 | Research Site | Quebec | Canada | G1S 4L8 | |
433 | Research Site | Beijing | China | 100006 | |
434 | Research Site | Beijing | China | 100021 | |
435 | Research Site | Beijing | China | 100730 | |
436 | Research Site | Changchun | China | 130061 | |
437 | Research Site | Chengdu | China | 610041 | |
438 | Research Site | Fuzhou | China | 350001 | |
439 | Research Site | Guangzhou | China | 510100 | |
440 | Research Site | Hangzhou | China | 310003 | |
441 | Research Site | Hangzhou | China | 310022 | |
442 | Research Site | Harbin | China | 150081 | |
443 | Research Site | Jinan | China | 2501117 | |
444 | Research Site | Nanjing | China | 210029 | |
445 | Research Site | Shanghai | China | 200025 | |
446 | Research Site | Shanghai | China | 200032 | |
447 | Research Site | Shijiazhuang | China | 050020 | |
448 | Research Site | Tianjin | China | 300060 | |
449 | Research Site | Avignon | France | 84918 | |
450 | Research Site | Besancon | France | 25030 | |
451 | Research Site | Bordeaux Cedex | France | 33000 | |
452 | Research Site | Brest Cedex | France | 29609 | |
453 | Research Site | Caen Cedex 05 | France | 14076 | |
454 | Research Site | Clermont Ferrand cedex 01 | France | 63011 | |
455 | Research Site | Dechy | France | 59187 | |
456 | Research Site | La Roche sur Yon | France | 85025 | |
457 | Research Site | Lille Cedex | France | 59020 | |
458 | Research Site | Limoges Cedex | France | 87042 | |
459 | Research Site | Lyon Cedex 08 | France | 69373 | |
460 | Research Site | Marseille cedex 09 | France | 13273 | |
461 | Research Site | Marseille | France | ||
462 | Research Site | Montpellier | France | 34298 | |
463 | Research Site | Nantes | France | 44202 | |
464 | Research Site | Nice | France | 06100 | |
465 | Research Site | Paris Cedex 10 | France | 75010 | |
466 | Research Site | Plerin SUR MER | France | 22190 | |
467 | Research Site | Rennes | France | 35042 | |
468 | Research Site | Rouen | France | 76038 | |
469 | Research Site | Saint Cloud | France | 92211 | |
470 | Research Site | STRASBOURG Cedex | France | 67065 | |
471 | Research Site | Toulouse Cedex 3 | France | 31076 | |
472 | Research Site | Villejuif Cedex | France | 94805 | |
473 | Research Site | Aachen | Germany | 52074 | |
474 | Research Site | Augsburg | Germany | 86150 | |
475 | Research Site | Baden-Baden | Germany | 76532 | |
476 | Research Site | Berlin | Germany | 10117 | |
477 | Research Site | Berlin | Germany | 10367 | |
478 | Research Site | Berlin | Germany | 13125 | |
479 | Research Site | Berlin | Germany | 13589 | |
480 | Research Site | Berlin | Germany | 14169 | |
481 | Research Site | Bonn | Germany | 53113 | |
482 | Research Site | Bottrop | Germany | 46236 | |
483 | Research Site | Brandenburg | Germany | 14770 | |
484 | Research Site | Bremen | Germany | 28177 | |
485 | Research Site | Chemnitz | Germany | 09116 | |
486 | Research Site | Deggendorf | Germany | 94469 | |
487 | Research Site | Dresden | Germany | 01307 | |
488 | Research Site | Düsseldorf | Germany | 40225 | |
489 | Research Site | Düsseldorf | Germany | 40235 | |
490 | Research Site | Ebersberg | Germany | 85560 | |
491 | Research Site | Eggenfelden | Germany | 84307 | |
492 | Research Site | Erfurt | Germany | 99085 | |
493 | Research Site | Erlangen | Germany | 91054 | |
494 | Research Site | Essen | Germany | 45136 | |
495 | Research Site | Essen | Germany | 45147 | |
496 | Research Site | Esslingen am Neckar | Germany | 73730 | |
497 | Research Site | Frankfurt am Main | Germany | 65929 | |
498 | Research Site | Freiburg im Breisgau | Germany | 79106 | |
499 | Research Site | Fulda | Germany | 36043 | |
500 | Research Site | Fürth | Germany | 90766 | |
501 | Research Site | Gera | Germany | 07548 | |
502 | Research Site | Gifhorn | Germany | 38518 | |
503 | Research Site | Halle | Germany | 06120 | |
504 | Research Site | Hamburg | Germany | 20246 | |
505 | Research Site | Hameln | Germany | 31785 | |
506 | Research Site | Hannover | Germany | 30177 | |
507 | Research Site | Hannover | Germany | 30559 | |
508 | Research Site | Hannover | Germany | 30625 | |
509 | Research Site | Hildesheim | Germany | 31134 | |
510 | Research Site | Karlsruhe | Germany | 76135 | |
511 | Research Site | Kassel | Germany | 34117 | |
512 | Research Site | Koblenz Am Rhein | Germany | 56068 | |
513 | Research Site | Köln | Germany | 50924 | |
514 | Research Site | Leipzig | Germany | 04103 | |
515 | Research Site | Mainz Am Rhein | Germany | 55131 | |
516 | Research Site | Mannheim | Germany | 68167 | |
517 | Research Site | Memmingen | Germany | 87700 | |
518 | Research Site | Mühlhausen | Germany | 99974 | |
519 | Research Site | Mühlheim An Der Ruhr | Germany | 45468 | |
520 | Research Site | München | Germany | 80337 | |
521 | Research Site | München | Germany | 80634 | |
522 | Research Site | München | Germany | 81675 | |
523 | Research Site | Münster | Germany | 48149 | |
524 | Research Site | Nordhausen | Germany | 99734 | |
525 | Research Site | Offenbach am Main | Germany | 63069 | |
526 | Research Site | Onkologisch Hämatologische Sch | Germany | 28209 | |
527 | Research Site | Paderborn | Germany | 33098 | |
528 | Research Site | Ravensburg | Germany | 88212 | |
529 | Research Site | Recklinghausen | Germany | 45659 | |
530 | Research Site | Rostock | Germany | 18059 | |
531 | Research Site | Rotenburg | Germany | 27356 | |
532 | Research Site | Saarbrücken | Germany | 66113 | |
533 | Research Site | Schweinfurt | Germany | 97421 | |
534 | Research Site | Stendal | Germany | 39576 | |
535 | Research Site | Tübingen | Germany | 72076 | |
536 | Research Site | Ulm | Germany | 89075 | |
537 | Research Site | Witten | Germany | 58452 | |
538 | Research Site | Budapest | Hungary | 1122 | |
539 | Research Site | Budapest | Hungary | 1145 | |
540 | Research Site | Reykjavík | Iceland | 101 | |
541 | Research Site | Jerusalem | Israel | 91120 | |
542 | Research Site | Petah Tikva | Israel | 49100 | |
543 | Research Site | Ramat Gan | Israel | 5265601 | |
544 | Research Site | Tel-Aviv | Israel | 6423906 | |
545 | Research Site | Bergamo | Italy | 24127 | |
546 | Research Site | Bologna | Italy | 40138 | |
547 | Research Site | Bolzano | Italy | 39100 | |
548 | Research Site | Castellanza Varese | Italy | 21053 | |
549 | Research Site | Lecce | Italy | 73100 | |
550 | Research Site | Legnago | Italy | 37045 | |
551 | Research Site | Milano | Italy | 20132 | |
552 | Research Site | Milano | Italy | 20141 | |
553 | Research Site | Modena | Italy | 41124 | |
554 | Research Site | Napoli | Italy | 80131 | |
555 | Research Site | Nehrar | Italy | 37024 | |
556 | Research Site | Padova | Italy | 35128 | |
557 | Research Site | Palermo | Italy | 90146 | |
558 | Research Site | Pavia | Italy | 27100 | |
559 | Research Site | Perugia | Italy | 6156 | |
560 | Research Site | Prato | Italy | 59100 | |
561 | Research Site | Rimini | Italy | 47923 | |
562 | Research Site | Saronno | Italy | 21047 | |
563 | Research Site | Varese | Italy | 21100 | |
564 | Research Site | Viterbo | Italy | 01100 | |
565 | Research Site | Chiba-shi | Japan | 260-8717 | |
566 | Research Site | Chuo-ku | Japan | 104-0045 | |
567 | Research Site | Chuo-ku | Japan | 104-8560 | |
568 | Research Site | Fukuoka-shi | Japan | 811-1395 | |
569 | Research Site | Hidaka-shi | Japan | 350-1298 | |
570 | Research Site | Hiroshima-shi | Japan | 730-8518 | |
571 | Research Site | Isehara-shi | Japan | 259-1193 | |
572 | Research Site | Kagoshima-shi | Japan | 892-0833 | |
573 | Research Site | Kashiwa | Japan | 277-8577 | |
574 | Research Site | Kawasaki-shi | Japan | 216-8511 | |
575 | Research Site | Koto-ku | Japan | 135-8550 | |
576 | Research Site | Kyoto-shi | Japan | 606-8507 | |
577 | Research Site | Matsuyama-shi | Japan | 791-0280 | |
578 | Research Site | Morioka-shi | Japan | 028-3695 | |
579 | Research Site | Nagoya-shi | Japan | 464-8681 | |
580 | Research Site | Nagoya-shi | Japan | 467-8602 | |
581 | Research Site | Nankoku-shi | Japan | 783-8505 | |
582 | Research Site | Niigata-shi | Japan | 951-8566 | |
583 | Research Site | Osaka-city | Japan | 540-0006 | |
584 | Research Site | Osaka-shi | Japan | 541-8567 | |
585 | Research Site | Ota-shi | Japan | 373-8550 | |
586 | Research Site | Sapporo-shi | Japan | 003-0804 | |
587 | Research Site | Shinagawa-ku | Japan | 142-8666 | |
588 | Research Site | Shizuoka | Japan | 411-8777 | |
589 | Research Site | Suita-city | Japan | 565-0871 | |
590 | Research Site | Daegu | Korea, Republic of | 41404 | |
591 | Research Site | Goyang-si | Korea, Republic of | 10408 | |
592 | Research Site | Incheon | Korea, Republic of | 21565 | |
593 | Research Site | Seongnam-si | Korea, Republic of | 13620 | |
594 | Research Site | Seoul | Korea, Republic of | 03080 | |
595 | Research Site | Seoul | Korea, Republic of | 03722 | |
596 | Research Site | Seoul | Korea, Republic of | 05505 | |
597 | Research Site | Seoul | Korea, Republic of | 135-710 | |
598 | Research Site | Seoul | Korea, Republic of | 158-710 | |
599 | Research Site | Amsterdam | Netherlands | 1066 CX | |
600 | Research Site | Breda | Netherlands | 4819 EV | |
601 | Research Site | Geleen | Netherlands | 6162 BG | |
602 | Research Site | Leiden | Netherlands | 2333 ZA | |
603 | Research Site | Maastricht | Netherlands | 6202 AZ | |
604 | Research Site | Rotterdam | Netherlands | 3015 GD | |
605 | Research Site | Zaandam | Netherlands | 1502 DV | |
606 | Research Site | Gdańsk | Poland | 80-214 | |
607 | Research Site | Grzepnica | Poland | 72-003 | |
608 | Research Site | Olsztyn | Poland | 10-228 | |
609 | Research Site | Poznan | Poland | 60-693 | |
610 | Research Site | Warszawa | Poland | 01-748 | |
611 | Research Site | Warszawa | Poland | 02-781 | |
612 | Research Site | Łódź | Poland | 93-338 | |
613 | Research Site | Lisboa | Portugal | 1099-023 | |
614 | Research Site | Lisboa | Portugal | 1400-038 | |
615 | Research Site | Lisboa | Portugal | 1500-650 | |
616 | Research Site | Lisboa | Portugal | 1998-018 | |
617 | Research Site | Loures | Portugal | 2674-514 | |
618 | Research Site | Porto | Portugal | 4200-072 | |
619 | Research Site | San Juan | Puerto Rico | 00936 | |
620 | Research Site | A Coruña | Spain | 15006 | |
621 | Research Site | Avila | Spain | 5004 | |
622 | Research Site | Badajoz | Spain | 06008 | |
623 | Research Site | Badalona | Spain | 08916 | |
624 | Research Site | Barcelona | Spain | 08025 | |
625 | Research Site | Barcelona | Spain | 08028 | |
626 | Research Site | Barcelona | Spain | 08035 | |
627 | Research Site | Castelló de la Plana | Spain | 12002 | |
628 | Research Site | Cáceres | Spain | 10003 | |
629 | Research Site | Córdoba | Spain | 14004 | |
630 | Research Site | Elche(Alicante) | Spain | 03202 | |
631 | Research Site | Girona | Spain | 17007 | |
632 | Research Site | Hosp de Llobregat(Barcelona) | Spain | 08907 | |
633 | Research Site | Jaén | Spain | 23007 | |
634 | Research Site | La Laguna (Tenerife) | Spain | 38320 | |
635 | Research Site | Lugo | Spain | 27003 | |
636 | Research Site | Lérida | Spain | 25198 | |
637 | Research Site | Madrid | Spain | 28007 | |
638 | Research Site | Madrid | Spain | 28033 | |
639 | Research Site | Madrid | Spain | 28034 | |
640 | Research Site | Madrid | Spain | 28040 | |
641 | Research Site | Madrid | Spain | 28041 | |
642 | Research Site | Malaga | Spain | 29010 | |
643 | Research Site | Palma de Mallorca | Spain | 07010 | |
644 | Research Site | Pamplona | Spain | 31008 | |
645 | Research Site | Pozuelo de Alarcon | Spain | 28223 | |
646 | Research Site | Reus,Tarragona | Spain | 43204 | |
647 | Research Site | Sabadell(Barcelona) | Spain | 08208 | |
648 | Research Site | Salamanca | Spain | 37007 | |
649 | Research Site | San Sebastián | Spain | 20014 | |
650 | Research Site | Santiago de Compostela | Spain | 15706 | |
651 | Research Site | Sevilla | Spain | 41009 | |
652 | Research Site | Sevilla | Spain | 41013 | |
653 | Research Site | Terrassa(Barcelona) | Spain | 08227 | |
654 | Research Site | Toledo | Spain | 45004 | |
655 | Research Site | Valencia | Spain | 46009 | |
656 | Research Site | Valencia | Spain | 46010 | |
657 | Research Site | Zaragoza | Spain | 50009 | |
658 | Research Site | Göteborg | Sweden | 413 45 | |
659 | Research Site | Linköping | Sweden | 581 85 | |
660 | Research Site | Lund | Sweden | 221 85 | |
661 | Research Site | Solna | Sweden | 171 64 | |
662 | Research Site | Stockholm | Sweden | 118 83 | |
663 | Research Site | Umeå | Sweden | 90185 | |
664 | Research Site | Bern | Switzerland | 3010 | |
665 | Research Site | Lausanne | Switzerland | 1011 | |
666 | Research Site | Zürich | Switzerland | 8091 | |
667 | Research Site | Changhua | Taiwan | 50006 | |
668 | Research Site | Kaohsiung | Taiwan | 80756 | |
669 | Research Site | Taichung | Taiwan | 40447 | |
670 | Research Site | Taichung | Taiwan | 407 | |
671 | Research Site | Tainan City | Taiwan | 70403 | |
672 | Research Site | Tainan City | Taiwan | 73657 | |
673 | Research Site | Taipei | Taiwan | 10048 | |
674 | Research Site | Taipei | Taiwan | 10449 | |
675 | Research Site | Taipei | Taiwan | 11217 | |
676 | Research Site | Taipei | Taiwan | 11490 | |
677 | Research Site | Taoyuan | Taiwan | 333 | |
678 | Research Site | Belfast | United Kingdom | BT9 7AB | |
679 | Research Site | Birmingham | United Kingdom | B15 2TH | |
680 | Research Site | Bournemouth | United Kingdom | BH7 7DW | |
681 | Research Site | Bristol | United Kingdom | BS2 8ED | |
682 | Research Site | Cambridge | United Kingdom | CB2 0QQ | |
683 | Research Site | Cardiff. | United Kingdom | CF14 2TL | |
684 | Research Site | Dudley | United Kingdom | DY1 2HQ | |
685 | Research Site | Edinburgh | United Kingdom | EH4 2XR | |
686 | Research Site | Glasgow | United Kingdom | G12 0YN | |
687 | Research Site | Leeds | United Kingdom | LS9 7TF | |
688 | Research Site | London | United Kingdom | E1 1BB | |
689 | Research Site | London | United Kingdom | NW1 2PG | |
690 | Research Site | London | United Kingdom | SE1 9RT | |
691 | Research Site | London | United Kingdom | SW17 0QT | |
692 | Research Site | London | United Kingdom | SW3 6JJ | |
693 | Research Site | Manchester | United Kingdom | M20 4GJ | |
694 | Research Site | Nottingham | United Kingdom | NG5 1PB | |
695 | Research Site | Oxford | United Kingdom | OX3 7LE | |
696 | Research Site | Sheffield | United Kingdom | S10 2SJ | |
697 | Research Site | Southampton | United Kingdom | SO16 6YD | |
698 | Research Site | Stoke-on-Trent | United Kingdom | ST4 6QG | |
699 | Research Site | Sutton | United Kingdom | SM2 5PT |
Sponsors and Collaborators
- AstraZeneca
- Breast International Group
- Frontier Science & Technology Research Foundation, Inc.
- NRG Oncology
- Myriad Genetic Laboratories, Inc.
- Br.E.A.S.T. -Data Center & Operational Office Institut Jules Bordet
- Merck Sharp & Dohme LLC
Investigators
- Principal Investigator: Andrew Tutt, Doctor of Medicine, Integrated Cancer Centre Guy's Hospital, King's College, London School of Medicine, London, UK
- Principal Investigator: Judy Garber, Doctor of Medicine, Harvard Medical School, Center for Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Susan F. Smither Center for Women's Cancers, 450 Brookline Avenue, Boston; MA 02215, US
- Principal Investigator: Charles Geyer, Doctor of Medicine, Virginia Commonwealth University Massey Cancer Center, McGlothlin Medical Education Center, Room 12-217, 1201 East Marshall St., PO Box 980070, Richmond, VA 23298-0070, USA
Study Documents (Full-Text)
More Information
Additional Information:
- AstraZeneca Cancer Study Locator Service Phone: 877 400 4656 Email: astrazeneca@emergingmed.com
- Related Info
Publications
None provided.- D081CC00006
- NSABP B-55
- BIG 6-13
Study Results
Participant Flow
Recruitment Details | The first patient was enrolled on 22 April 2014. Patients were randomised from 546 centres in 23 countries worldwide. |
---|---|
Pre-assignment Detail | Patients with unknown germline BRCA (gBRCA) mutation status prior to randomisation underwent Screening Part 1 to ascertain gBRCA mutation status during, or prior to, neoadjuvant/adjuvant chemotherapy. All patients with known gBRCA mutation status (including those found through Screening Part 1) underwent Screening Part 2. |
Arm/Group Title | Olaparib | Placebo |
---|---|---|
Arm/Group Description | Olaparib tablets 300mg taken orally twice daily. | Placebo tablets taken orally twice daily. |
Period Title: Overall Study | ||
STARTED | 921 | 915 |
COMPLETED | 0 | 0 |
NOT COMPLETED | 921 | 915 |
Baseline Characteristics
Arm/Group Title | Olaparib | Placebo | Total |
---|---|---|---|
Arm/Group Description | Olaparib tablets 300mg taken orally twice daily. | Placebo tablets taken orally twice daily. | Total of all reporting groups |
Overall Participants | 921 | 915 | 1836 |
Age (Years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [Years] |
43.0
(9.8)
|
43.6
(10.1)
|
43.3
(10.0)
|
Age, Customized (Number) [Number] | |||
<30 years |
51
5.5%
|
59
6.4%
|
110
6%
|
30-39 years |
333
36.2%
|
306
33.4%
|
639
34.8%
|
40-49 years |
315
34.2%
|
308
33.7%
|
623
33.9%
|
50-59 years |
166
18%
|
172
18.8%
|
338
18.4%
|
60-69 years |
48
5.2%
|
66
7.2%
|
114
6.2%
|
>=70 years |
8
0.9%
|
4
0.4%
|
12
0.7%
|
Sex: Female, Male (Count of Participants) | |||
Female |
919
99.8%
|
911
99.6%
|
1830
99.7%
|
Male |
2
0.2%
|
4
0.4%
|
6
0.3%
|
Race/Ethnicity, Customized (Number) [Number] | |||
HISPANIC OR LATINO |
34
3.7%
|
24
2.6%
|
58
3.2%
|
NOT HISPANIC OR LATINO |
805
87.4%
|
812
88.7%
|
1617
88.1%
|
NOT KNOWN, NOT RECORDED, OR REFUSED |
82
8.9%
|
79
8.6%
|
161
8.8%
|
Race/Ethnicity, Customized (Number) [Number] | |||
AMERICAN INDIAN OR ALASKA NATIVE |
3
0.3%
|
1
0.1%
|
4
0.2%
|
ASIAN |
259
28.1%
|
272
29.7%
|
531
28.9%
|
BLACK OR AFRICAN AMERICAN |
19
2.1%
|
29
3.2%
|
48
2.6%
|
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER |
1
0.1%
|
0
0%
|
1
0.1%
|
WHITE |
626
68%
|
599
65.5%
|
1225
66.7%
|
OTHER |
3
0.3%
|
6
0.7%
|
9
0.5%
|
MISSING |
10
1.1%
|
8
0.9%
|
18
1%
|
Region of Enrollment (Number) [Number] | |||
Argentina |
16
1.7%
|
12
1.3%
|
28
1.5%
|
Australia |
30
3.3%
|
30
3.3%
|
60
3.3%
|
Austria |
28
3%
|
25
2.7%
|
53
2.9%
|
Belgium |
12
1.3%
|
26
2.8%
|
38
2.1%
|
Canada |
11
1.2%
|
23
2.5%
|
34
1.9%
|
China |
117
12.7%
|
130
14.2%
|
247
13.5%
|
France |
77
8.4%
|
65
7.1%
|
142
7.7%
|
Germany |
106
11.5%
|
92
10.1%
|
198
10.8%
|
United Kingdom |
60
6.5%
|
46
5%
|
106
5.8%
|
Hungary |
8
0.9%
|
9
1%
|
17
0.9%
|
Iceland |
5
0.5%
|
1
0.1%
|
6
0.3%
|
Israel |
30
3.3%
|
35
3.8%
|
65
3.5%
|
Italy |
30
3.3%
|
27
3%
|
57
3.1%
|
Japan |
64
6.9%
|
76
8.3%
|
140
7.6%
|
Netherlands |
11
1.2%
|
18
2%
|
29
1.6%
|
Poland |
50
5.4%
|
59
6.4%
|
109
5.9%
|
Portugal |
7
0.8%
|
6
0.7%
|
13
0.7%
|
Korea, Republic Of |
53
5.8%
|
44
4.8%
|
97
5.3%
|
Spain |
63
6.8%
|
46
5%
|
109
5.9%
|
Sweden |
20
2.2%
|
15
1.6%
|
35
1.9%
|
Switzerland |
4
0.4%
|
17
1.9%
|
21
1.1%
|
Taiwan, Province Of China |
8
0.9%
|
4
0.4%
|
12
0.7%
|
United States |
111
12.1%
|
109
11.9%
|
220
12%
|
Outcome Measures
Title | Invasive Disease Free Survival (IDFS) |
---|---|
Description | An IDFS event is defined as the first occurrence of loco-regional or distant recurrence or new cancer or death from any cause. |
Time Frame | From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months) |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set (FAS) |
Arm/Group Title | Olaparib | Placebo |
---|---|---|
Arm/Group Description | Olaparib tablets 300mg taken orally twice daily. | Placebo tablets taken orally twice daily. |
Measure Participants | 921 | 915 |
Count of Participants [Participants] |
106
11.5%
|
178
19.5%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Olaparib, Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0000073 |
Comments | A multiple testing procedure is employed across the primary and all key secondary endpoints to strongly control overall type I error at 5% (2 sided) accounting for all analysis timepoints. | |
Method | Log Rank | |
Comments | Log rank test is stratified by chemotherapy type, hormone receptor status, and prior platinum therapy using a pre-specified pooling strategy. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.581 | |
Confidence Interval |
(2-Sided) 99.5% 0.409 to 0.816 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Estimate of the treatment hazard ratio is based on a stratified Cox's Proportional Hazards Model, <1 indicates a lower risk with olaparib compared with placebo arm. Stratification factors are the same as those used in the stratified log-rank test. |
Title | Distant Disease Free Survival (DDFS) |
---|---|
Description | A DDFS event is defined as documented evidence of first distant recurrence of breast cancer or death from any cause |
Time Frame | From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months) |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set (FAS) |
Arm/Group Title | Olaparib | Placebo |
---|---|---|
Arm/Group Description | Olaparib tablets 300mg taken orally twice daily. | Placebo tablets taken orally twice daily. |
Measure Participants | 921 | 915 |
Count of Participants [Participants] |
89
9.7%
|
152
16.6%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Olaparib, Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0000257 |
Comments | A multiple testing procedure is employed across the primary and all key secondary endpoints to strongly control overall type I error at 5% (2 sided) accounting for all analysis timepoints. | |
Method | Log Rank | |
Comments | Log rank test is stratified by chemotherapy type, hormone receptor status, and prior platinum therapy using a pre-specified pooling strategy. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.574 | |
Confidence Interval |
(2-Sided) 99.5% 0.392 to 0.831 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Estimate of the treatment hazard ratio is based on a stratified Cox's Proportional Hazards Model, <1 indicates a lower risk with olaparib compared with placebo arm. Stratification factors are the same as those used in the stratified log-rank test. |
Title | Overall Survival (OS) |
---|---|
Description | An OS event is defined as death by any cause. |
Time Frame | From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months) |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set (FAS) |
Arm/Group Title | Olaparib | Placebo |
---|---|---|
Arm/Group Description | Olaparib tablets 300mg taken orally twice daily. | Placebo tablets taken orally twice daily. |
Measure Participants | 921 | 915 |
Count of Participants [Participants] |
59
6.4%
|
86
9.4%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Olaparib, Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0236 |
Comments | A multiple testing procedure is employed across the primary and all key secondary endpoints to strongly control overall type I error at 5% (2 sided) accounting for all analysis timepoints. | |
Method | Log Rank | |
Comments | Log rank test is stratified by chemotherapy type, hormone receptor status, and prior platinum therapy using a pre-specified pooling strategy. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.683 | |
Confidence Interval |
(2-Sided) 99% 0.438 to 1.053 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Estimate of the treatment hazard ratio is based on a stratified Cox's Proportional Hazards Model, <1 indicates a lower risk with olaparib compared with placebo arm. Stratification factors are the same as those used in the stratified log-rank test. |
Title | Number of Participants With Contralateral Breast Cancers, New Primary Ovarian Cancer, New Primary Fallopian Tube Cancer and New Primary Peritoneal Cancer |
---|---|
Description | Number of patients with contralateral invasive breast cancer, contralateral non-invasive breast cancer, new primary ovarian cancer, new primary fallopian tube cancer and new primary peritoneal cancer. Analysis of contralateral breast cancers exclude patients with a bilateral mastectomy prior to randomisation. Analysis of new primary ovarian cancers excludes male patients and patients with a bilateral oophorectomy prior to randomisation. Analysis of new primary fallopian tube cancer excludes male patients and patients with a bilateral salpingectomy prior to randomisation. Analysis of new primary peritoneal cancers excludes male patients. |
Time Frame | From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months) |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set (FAS) |
Arm/Group Title | Olaparib | Placebo |
---|---|---|
Arm/Group Description | Olaparib tablets 300mg taken orally twice daily. | Placebo tablets taken orally twice daily. |
Measure Participants | 921 | 915 |
Contralateral invasive breast cancer |
11
1.2%
|
14
1.5%
|
Contralateral non-invasive breast cancer |
2
0.2%
|
3
0.3%
|
New primary ovarian cancer |
1
0.1%
|
4
0.4%
|
New primary fallopian tube cancer |
1
0.1%
|
4
0.4%
|
New primary peritoneal cancer |
0
0%
|
0
0%
|
Title | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Neoadjuvant Chemotherapy |
---|---|
Description | Change from baseline for FACIT-Fatigue Score at 6 and 12 months for patients who completed neoadjuvant chemotherapy. Adjusted least-square mean changes and 95% Confidence Interval (CI) are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. FACIT-Fatigue score ranges from 0 to 52 with higher score indicating less fatigue. |
Time Frame | 6 and 12 months after randomisation |
Outcome Measure Data
Analysis Population Description |
---|
Patient reported outcomes (PRO) Analysis Set |
Arm/Group Title | Olaparib | Placebo |
---|---|---|
Arm/Group Description | Olaparib tablets 300mg taken orally twice daily. | Placebo tablets taken orally twice daily. |
Measure Participants | 371 | 356 |
Change from baseline FACIT-Fatigue Score to 6 months |
-1.5
|
-0.2
|
Change from baseline FACIT-Fatigue Score to 12 months |
-1.5
|
0.0
|
Title | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Adjuvant Chemotherapy |
---|---|
Description | Change from baseline for FACIT-Fatigue Score at 6 and 12 months for patients who completed adjuvant chemotherapy. Adjusted least-square mean changes and 95% CI are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. FACIT-Fatigue score ranges from 0 to 52 with higher score indicating less fatigue. |
Time Frame | 6 and 12 months after randomisation |
Outcome Measure Data
Analysis Population Description |
---|
Patient reported outcomes (PRO) Analysis Set |
Arm/Group Title | Olaparib | Placebo |
---|---|---|
Arm/Group Description | Olaparib tablets 300mg taken orally twice daily. | Placebo tablets taken orally twice daily. |
Measure Participants | 375 | 403 |
Change from baseline FACIT-Fatigue Score to 6 months |
-0.7
|
0.6
|
Change from baseline FACIT-Fatigue Score to 12 months |
-0.8
|
0.5
|
Title | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Neoadjuvant Chemotherapy |
---|---|
Description | Change from baseline for EORTC QLQ-C30 Global health status QOL (Quality of Life) Score at 6 and 12 months for patients who completed neoadjuvant chemotherapy. Adjusted least-square mean changes and 95% CI are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. EORTC QLQ-C30 scores range from 0 to 100 with higher score indicating better quality of life. |
Time Frame | 6 and 12 months after randomisation |
Outcome Measure Data
Analysis Population Description |
---|
Patient reported outcomes (PRO) Analysis Set |
Arm/Group Title | Olaparib | Placebo |
---|---|---|
Arm/Group Description | Olaparib tablets 300mg taken orally twice daily. | Placebo tablets taken orally twice daily. |
Measure Participants | 380 | 358 |
Change from baseline EORTC QLQ-C30 Global health status score to 6 months |
-0.2
|
0.5
|
Change from baseline EORTC QLQ-C30 Global health status score to 12 months |
0.4
|
2.8
|
Title | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Adjuvant Chemotherapy |
---|---|
Description | Change from baseline for EORTC QLQ-C30 Global health status QOL (Quality of Life) Score at 6 and 12 months for patients who completed adjuvant chemotherapy. Adjusted least-square mean changes and 95% CI are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. EORTC QLQ-C30 scores range from 0 to 100 with higher score indicating better quality of life. |
Time Frame | 6 and 12 months after randomisation |
Outcome Measure Data
Analysis Population Description |
---|
Patient reported outcomes (PRO) Analysis Set |
Arm/Group Title | Olaparib | Placebo |
---|---|---|
Arm/Group Description | Olaparib tablets 300mg taken orally twice daily. | Placebo tablets taken orally twice daily. |
Measure Participants | 383 | 406 |
Change from baseline EORTC QLQ-C30 Global health status score to 6 months |
-0.4
|
2.3
|
Change from baseline EORTC QLQ-C30 Global health status score to 12 months |
0.7
|
3.3
|
Adverse Events
Time Frame | Maximum of approximately 13 months | |||
---|---|---|---|---|
Adverse Event Reporting Description | All-Cause Mortality was collected for the Full Analysis Set (FAS). Serious and Other Adverse Events were collected for the Safety Analysis Set (SAS), which includes all participants who received at least 1 dose of randomized study treatment (N=1815). There were 10 patients in the olaparib arm and 11 patients in the placebo arm that did not receive study treatment and therefore are excluded from the SAS. The Other Adverse Events section reports AE's of any grade where the frequency is above 5%. | |||
Arm/Group Title | Olaparib | Placebo | ||
Arm/Group Description | Olaparib tablets 300mg taken orally twice daily. | Placebo tablets taken orally twice daily. | ||
All Cause Mortality |
||||
Olaparib | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 59/921 (6.4%) | 86/915 (9.4%) | ||
Serious Adverse Events |
||||
Olaparib | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 79/911 (8.7%) | 76/904 (8.4%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 15/911 (1.6%) | 17 | 1/904 (0.1%) | 1 |
Febrile neutropenia | 3/911 (0.3%) | 3 | 0/904 (0%) | 0 |
Cardiac disorders | ||||
Acute myocardial infarction | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Angina pectoris | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Cardiac arrest | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Cardiac failure | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Cardiac failure congestive | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Coronary artery disease | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Coronary artery dissection | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Myocardial infarction | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Pericardial effusion | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Ear and labyrinth disorders | ||||
Deafness | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Sudden hearing loss | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Endocrine disorders | ||||
Hypothyroidism | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Eye disorders | ||||
Vision blurred | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Gastrointestinal disorders | ||||
Abdominal pain | 0/911 (0%) | 0 | 3/904 (0.3%) | 3 |
Chronic gastritis | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Colitis | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Diarrhoea | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Intestinal prolapse | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Large intestine polyp | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Melaena | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Nausea | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Small intestinal obstruction | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Vomiting | 2/911 (0.2%) | 2 | 0/904 (0%) | 0 |
General disorders | ||||
Chest pain | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Fatigue | 1/911 (0.1%) | 5 | 0/904 (0%) | 0 |
Foreign body reaction | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Impaired healing | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Non-cardiac chest pain | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Pyrexia | 1/911 (0.1%) | 1 | 3/904 (0.3%) | 3 |
Hepatobiliary disorders | ||||
Cholecystitis | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Cholecystitis acute | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Hepatic function abnormal | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Immune system disorders | ||||
Anaphylactic reaction | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Infections and infestations | ||||
Appendicitis | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Breast cellulitis | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Bronchitis | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Cellulitis | 1/911 (0.1%) | 1 | 2/904 (0.2%) | 3 |
Cystitis | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Device related infection | 3/911 (0.3%) | 3 | 2/904 (0.2%) | 2 |
Gastroenteritis | 2/911 (0.2%) | 2 | 0/904 (0%) | 0 |
Gingivitis | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Influenza | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Lower respiratory tract infection | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Lymphangitis | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Mastitis | 3/911 (0.3%) | 3 | 6/904 (0.7%) | 6 |
Pneumonia | 1/911 (0.1%) | 1 | 1/904 (0.1%) | 1 |
Urinary tract infection | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Wound infection | 2/911 (0.2%) | 2 | 1/904 (0.1%) | 1 |
Injury, poisoning and procedural complications | ||||
Craniocerebral injury | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Gastrointestinal procedural complication | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Post procedural haematoma | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Post procedural haemorrhage | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Radiation pneumonitis | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Ureteric injury | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Vascular access complication | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Wound complication | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Wound dehiscence | 1/911 (0.1%) | 1 | 4/904 (0.4%) | 4 |
Investigations | ||||
Blood bilirubin increased | 0/911 (0%) | 0 | 1/904 (0.1%) | 3 |
Neutrophil count decreased | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Platelet count decreased | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Metabolism and nutrition disorders | ||||
Dehydration | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||
Back pain | 2/911 (0.2%) | 2 | 1/904 (0.1%) | 1 |
Bone pain | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Chest wall mass | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Intervertebral disc protrusion | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Acute myeloid leukaemia | 1/911 (0.1%) | 1 | 1/904 (0.1%) | 1 |
Benign breast neoplasm | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Breast cancer | 1/911 (0.1%) | 1 | 3/904 (0.3%) | 3 |
Breast cancer female | 0/911 (0%) | 0 | 2/904 (0.2%) | 2 |
Chest wall tumour | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Endometrial adenocarcinoma | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Fallopian tube cancer | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Fibroadenoma of breast | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Invasive lobular breast carcinoma | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Malignant melanoma | 1/911 (0.1%) | 1 | 4/904 (0.4%) | 4 |
Ovarian cancer | 0/911 (0%) | 0 | 4/904 (0.4%) | 4 |
Ovarian germ cell teratoma | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Nervous system disorders | ||||
Ataxia | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Cognitive disorder | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Dizziness | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Headache | 2/911 (0.2%) | 2 | 1/904 (0.1%) | 1 |
Lacunar infarction | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Migraine with aura | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Sciatica | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Syncope | 1/911 (0.1%) | 1 | 1/904 (0.1%) | 1 |
Vith nerve disorder | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Pregnancy, puerperium and perinatal conditions | ||||
Abortion spontaneous | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Product Issues | ||||
Device dislocation | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Psychiatric disorders | ||||
Bipolar disorder | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Depression | 0/911 (0%) | 0 | 2/904 (0.2%) | 2 |
Suicidal ideation | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Suicide attempt | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Renal and urinary disorders | ||||
Acute kidney injury | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Bladder disorder | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Nephrolithiasis | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Reproductive system and breast disorders | ||||
Breast disorder | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Breast fibrosis | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Breast mass | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Breast pain | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Dysfunctional uterine bleeding | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Endometrial hyperplasia | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Metrorrhagia | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Ovarian cyst | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Ovarian haemorrhage | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Uterine polyp | 1/911 (0.1%) | 1 | 1/904 (0.1%) | 1 |
Vaginal haemorrhage | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||
Cough | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Dyspnoea | 2/911 (0.2%) | 2 | 0/904 (0%) | 0 |
Lung disorder | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Pneumonitis | 2/911 (0.2%) | 2 | 1/904 (0.1%) | 1 |
Pneumothorax | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Surgical and medical procedures | ||||
Oophorectomy | 0/911 (0%) | 0 | 1/904 (0.1%) | 1 |
Vascular disorders | ||||
Embolism | 2/911 (0.2%) | 2 | 0/904 (0%) | 0 |
Lymphoedema | 1/911 (0.1%) | 1 | 0/904 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
Olaparib | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 791/911 (86.8%) | 668/904 (73.9%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 200/911 (22%) | 261 | 34/904 (3.8%) | 39 |
Gastrointestinal disorders | ||||
Abdominal pain | 86/911 (9.4%) | 96 | 65/904 (7.2%) | 77 |
Constipation | 84/911 (9.2%) | 89 | 77/904 (8.5%) | 87 |
Diarrhoea | 160/911 (17.6%) | 198 | 124/904 (13.7%) | 162 |
Dyspepsia | 55/911 (6%) | 62 | 37/904 (4.1%) | 39 |
Nausea | 518/911 (56.9%) | 680 | 211/904 (23.3%) | 265 |
Stomatitis | 81/911 (8.9%) | 116 | 36/904 (4%) | 38 |
Vomiting | 204/911 (22.4%) | 293 | 74/904 (8.2%) | 84 |
General disorders | ||||
Fatigue | 365/911 (40.1%) | 439 | 247/904 (27.3%) | 287 |
Influenza like illness | 57/911 (6.3%) | 64 | 43/904 (4.8%) | 55 |
Pain | 68/911 (7.5%) | 78 | 74/904 (8.2%) | 83 |
Pyrexia | 48/911 (5.3%) | 57 | 39/904 (4.3%) | 44 |
Infections and infestations | ||||
Nasopharyngitis | 31/911 (3.4%) | 45 | 52/904 (5.8%) | 74 |
Upper respiratory tract infection | 79/911 (8.7%) | 91 | 75/904 (8.3%) | 104 |
Investigations | ||||
Lymphocyte count decreased | 61/911 (6.7%) | 87 | 15/904 (1.7%) | 16 |
Neutrophil count decreased | 145/911 (15.9%) | 210 | 59/904 (6.5%) | 80 |
White blood cell count decreased | 143/911 (15.7%) | 210 | 52/904 (5.8%) | 69 |
Metabolism and nutrition disorders | ||||
Decreased appetite | 119/911 (13.1%) | 135 | 53/904 (5.9%) | 55 |
Musculoskeletal and connective tissue disorders | ||||
Arthralgia | 84/911 (9.2%) | 89 | 108/904 (11.9%) | 119 |
Back pain | 60/911 (6.6%) | 65 | 73/904 (8.1%) | 77 |
Myalgia | 50/911 (5.5%) | 58 | 49/904 (5.4%) | 50 |
Pain in extremity | 63/911 (6.9%) | 75 | 62/904 (6.9%) | 68 |
Nervous system disorders | ||||
Dizziness | 104/911 (11.4%) | 112 | 67/904 (7.4%) | 73 |
Dysgeusia | 107/911 (11.7%) | 125 | 38/904 (4.2%) | 41 |
Headache | 178/911 (19.5%) | 217 | 151/904 (16.7%) | 195 |
Psychiatric disorders | ||||
Insomnia | 67/911 (7.4%) | 71 | 61/904 (6.7%) | 65 |
Respiratory, thoracic and mediastinal disorders | ||||
Cough | 77/911 (8.5%) | 84 | 72/904 (8%) | 80 |
Vascular disorders | ||||
Hot flush | 72/911 (7.9%) | 75 | 75/904 (8.3%) | 77 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Restrictions are imposed by the trial's Steering Committee (SC) and intend to ensure that all publications/presentations are peer reviewed by the SC. Sponsor has the right to review/comment on the content of the material to be published/presented, may request removal of confidential information (e.g. patentable information/trade secrets) within max 90 days. Individual Institutions may publish/present data from their site(s) in compliance with conditions defined in Study Publication Policy.
Results Point of Contact
Name/Title | Global Clinical Lead |
---|---|
Organization | AstraZeneca |
Phone | 1-877-240-9479 |
information.center@astrazeneca.com |
- D081CC00006
- NSABP B-55
- BIG 6-13