Patients with the following solid malignancy: • Metastatic breast cancer • Metastatic prostate cancer • Metastatic lung cancer • Metastatic head and neck • Metastatic endometrial cancer • Metastatic clear cell renal cancer • Metastatic pancreatic cancer • Metastatic ovarian cancer • Metastatic urothelial carcinoma MedDRA version: 20.0 Level: LLT Classification code 10064049 Term: Lung adenocarcinoma metastatic System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classifi
Conditions
Interventions
Trade Name: Lynparza 100 mg film-coated Tablet
Product Name: OLAPARIB
Product Code: AZD2281
Pharmaceutical Form: Coated tablet
Product Name: DURVALUMAB
Product Code: MEDI4736
Pharmaceutical Form: Con
Sponsors
Centre Georges-François Leclerc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Exome sequencing of tumor and constitutive DNA should have been already performed during the previous medical care of the patient, with his consent, either as part of a clinical study or in accordance with the usual practice of the investigator site ,taking into account the mandatory list of HRR genes to be tested prior inclusion in the GUIDE2REPAIR study. 2. Patients must be diagnosed with a solid malignancy with the following cancer histologically confirmed with specified inclusion for each cohort: Metastatic breast cancer (In first and second line / third line and after), Metastatic lung cancer (Non-small cell lung cancer / Must have progressed after at least a first line with platinum based therapy), Metastatic head and Neck cancer (Must have progressed after at least a first line with platinum based therapy), Metastatic endometrial cancer (Progression after 1 prior systemic, platinum-based chemotherapy regimen for EC. Participants may have received up to 1 additional line of platinum-based chemotherapy if given in the neoadjuvant or adjuvant treatment setting. There is no restriction regarding prior hormonal therapy), Metastatic clear cell renal cancer (Must have progressed after at least a line with anti-angiogenic agent), Metastatic pancreatic cancer (Must have progressed after at least a line with FOLFIRINOX regimen and/or Gemcitabine based chemotherapy), Locally advanced or metastatic ovarian cancer (Must have received at least one and no more than two lines of prior platinum-containing therapy and progressed after the most recent platinum therapy in a platinum-sensitive timeframe (more than 6 months from the last dose of platinum before randomization)), Metastatic urothelial cancer (From the first line and regardless previous treatment), Metastatic prostate cancer (Documented evidence of metastatic castration resistant prostate cancer (mCRPC) / Ongoing therapy with LHRH analog or bilateral orchiectomy / Must have progressed on prior new hormonal agent (enzalutamine or abiraterone) and/or taxane chemotherapy). 3. Presence of mutation in homologous repair gene (homozygote mutation or heterozygote mutation and loss of heterozygosity of the second allele) (BRCA1, BRCA2, PALB2, ATM, FANCA, FANCB, FANCC, FANCE, FANCF, CHEK2, RAD51, BARD1, MRE11, RAD50, NBS1, HDAC2), LKB1/STK11, INPP4B, STAG2, ERG, CHEK1, BLM, LIG4, ATR, ATRX, CDK12 mutations are accepted. 4. Age >18 years at time of study entry. 5. Performance status ECOG of 0 or 1. 6. Life expectancy = 6 months. 7.At least one lesion measurable as defined by standard imaging criteria for the patient's tumor type (RECIST v1.1) that can be accurately assessed at baseline and is suitable for repeated assessment. 8. Body weight >30 kg. 9. Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment (cf. details in protocol). 10.Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1. 11.Male patients must use a condom during treatment of STEP1 (olaparib) and STEP2 (durvalumab + tremelimumab) and for 3 months after the last dose when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearin
Exclusion criteria
Exclusion criteria: 2. Patient with mBRCA1 / 2 that are eligible for current marketing authorization for olaparib (ovarian cancer),and patient eligible for AstraZeneca registration clinical trials, particularly for the prostate cohort. 3.Specific exclusion criteria each cohort: Metastatic breast cancer (Only for patient in first or second line : patient with mBRCA1 / 2 that are eligible for current marketing authorization for Olaparib (ovarian cancer) and patient eligible for AstraZeneca registration clinical trials), Metastatic lung cancer (Small cell cancer / oncogenic addiction : EGFR mutation or BRAF mutation or ALK rearrangement or ROS1 mutation) Locally advanced or metastatic ovarian cancer (Patient with mBRCA1 / 2 that are eligible for current marketing authorization for Olaparib (ovarian cancer) and patient eligible for AstraZeneca registration clinical trials), Metastatic prostate cancer (Untreated patients). 4.Participation in another clinical study with an investigational product during within 2 months of first administration of Olaparib. 6. Receipt of the last dose of anticancer therapy (chemotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) =21 days prior to the first dose of olaparib or 5 times its half-life, whichever is less. (cf. protocol for more details). 7. Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the exception of alopecia, ototoxicity, vitiligo, and the laboratory values defined in the inclusion criteria (cf. protocol for more details) 8. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non–cancer-related conditions (e.g., hormone replacement therapy) is acceptable. 9. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field (treatment field encompassing at least 30% of hematopoetic bone marrow) of radiation within 4 weeks of the first dose of study drug. (cf. protocol for more details). 10. Major surgical procedure within 28 days prior to the first dose of olaparib and patients must have recovered from any effects of any major surgery. (cf. protocol for more details). 11. Patients unable to swallow orally administered medication and patients with Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (cf. protocol for more details). 13. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). (cf. protocol for more details) 16. Concomitant use of known strong (cf. protocol for more details). 18. Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML. 19.History of another primary malignancy except for Malignancy treated with curative intent and with no known active disease =5 years before the first dose of IP and of low potential risk for recurrence, Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, Adequately treated carcinoma in situ without evidence of disease. 20. History of leptomeningeal carcinomatosis 21. Patient with symptomatic centra
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy, in terms of 6-month progression-free survival (PFS) rate for all cohorts except ovarian cohort where PFS will be evaluated at 12-month, of olaparib + immunotherapy (durvalumab + tremelimumab) during 4 months followed by durvalumab alone as maintenance in patients with solid cancer and in response or stable after prior molecular target therapy by olaparib based on molecular sequencing. Analyses will be performed independently in each cohort defined according to cancer location: breast, prostate, lung, ovarian, head and neck and other cancers;Secondary Objective: 1) To evaluate 6-month disease control rate (DCR) for all cohort and 12-month control rate for ovarian cohort 2) To evaluate 1 and 2-year PFS and overall survival (OS) 3) To evaluate response rate after 6 weeks of olaparib therapy (STEP 1) 4) To evaluate safety of molecular therapy by olaparib at the end of STEP1 5) To evaluate safety of molecular therapy (olaparib) + immunotherapy (durvalumab + tremelimumab) and immunotherapy in maintenance (durvalumab alone) ;Primary end point(s): Efficacy will be evaluated using progression free survival (PFS) 6 months after the initiation of immunotherapy for all cohorts excepted for ovarian cohort where PFS will be evaluated at 12 months. PFS is defined as the time from the date of first dose of immunotherapy to the date of progression or death from any cause. Progression will be defined using iRECIST criteria.;Timepoint(s) of evaluation of this end point: 6 months after the initiation of immunotherapy for all cohorts excepted for ovarian cohort where will be evaluated at 12 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Disease control rate include stable and responsive disease and will be evaluated 6 months after the initiation of immunotherapy for all cohort except for ovarian cohort evaluated at 12 months. 2) Overall survival (OS) will be evaluated at 12 months and 24 months after immunotherapy beginning defined by the time of the first dose of immunotherapy to the date of death from any cause. 3) Response rate will be evaluated by CT scan, RECIST evaluation after 6 weeks of Olaparib therapy. 4) Toxicity of olaparib will be evaluated at the end of STEP1 using CTCAE V5. 5) Toxicity of olaparib + immunotherapy (tremelimumab + durvalumab) will be evaluated at 3, 6 and 12 months after immunotherapy initiation using CTCAE V5. ;Timepoint(s) of evaluation of this end point: 1) 6 months after the initiation of immunotherapy for all cohort except for ovarian cohort evaluated at 12 months. 2) 12 months and 24 months. 3) 6 weeks after start of Olaparib (step 1). 4) At the end of step 1 (6 to 8 weeks of treatment by Olaparib). 5) 3, 6 and 12 months after start of treatment of step 2. | — |
Countries
France
Contacts
Public ContactHead of project /Emilie Rederstorff
Centre Georges-François Leclerc
Outcome results
None listed