Platinum Sensitive Recurrent High Grade Serous Ovarian/Primary Peritoneal or Fallopian tube Cancer MedDRA version: 20.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
University Health Network, Toronto
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically proven recurrent high grade serous ovarian/primary peritoneal or fallopian tube cancer. 2. Patients must have disease amenable to pre-operative biopsy. 3. Patients must have disease deemed suitable for surgical debulking. 4. Patients must have had at least one line of platinum based therapy, with a progression free interval of at least 6 months. 5. Patients must have shown platinum sensitivity to their last line of platinum therapy 6. Age =18 years. 7. ECOG performance status 0-1 within 7 days of registration 8. Life expectancy of greater than 3 months 9. Patients must have normal organ and marrow function as defined below within 7 days of registration: Hemoglobin =100 g/L Absolute neutrophil count =1.5 x 109/L Platelets =100 x 109/L Total bilirubin =1.5x ULN AST(SGOT) =2.5x ULN ALT(SGPT) =2.5x ULN Creatinine =1.5x ULN OR Creatinine clearance =60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. 10. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. 11. Ability to understand and the willingness to sign a written informed consent document. 12. Subject’s willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 36
Exclusion criteria
Exclusion criteria: 1. History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib. 2. History of allergic reactions attributed to platinum precluding further use. 3. Radiation therapy within 4 weeks of registration 4. Use of any other systemic, targeted, immunotherapy, chemotherapy, or investigational agents within 4 weeks of registration 5. Previously received a PARP inhibitor [prior use of Iniparib is allowed] 6. Other malignancy within the last 2 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, Grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for =2 years. Patients with a history of localized breast cancer may be eligible, provided they completed their adjuvant chemotherapy more than two years prior to registration, and that the patient remains free of recurrent or metastatic disease. 7. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent. 8. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication. Recent bowel obstruction is a contraindication to enrolment. 9. Concomitant use of known potent CYP3A4 inhibitors such as but not limited to ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir 10. Concomitant use of known potent CYP3A4 inducers such as but not limited to phenytoin, rifampicin, rifapentin, rifabutin, carbamazepine, phenobarbital, nevirapine, modafinil, St. John’s Wort (Hypericum perforatum) 11. No other anti-cancer therapy including immunotherapy, hormonal therapy, biological therapy, other novel agents or investigational agents is to be permitted 12. Persistent toxicities (CTCAE v 4.03 grade >2) caused by previous cancer therapy, excluding alopecia 13. Patients with myelodysplastic syndrome/acute myeloid leukemia 14. Patients with brain metastases 15. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) 16. Patients with known active hepatitis (i.e., hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids 17. Pregnant or breastfeeding women are excluded. 18. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • Assess the safety and tolerability of pre-operative Olaparib. • Assess the response rate to olaparib in the neoadjuvant period. • Assess PFS and PFS2 with olaparib in comparison to platinum based chemotherapy • Assess the value of ctDNA as a prognostic factor alone and in comparison to CA125 • Evaluate gene expression change in tumour tissue before and after treatment with Olaparib • Assess secondary mutation rate in surgical tumour specimens following PARP therapy and at progression. • Evaluate changes in blood based biomarkers using ctDNA before, during and after treatment with Olaparib in an attempt to correlate with gene expression changes, BRCA mutation status and histopathological changes. ;Primary end point(s): • Biological effects in the primary tumour following a short pre-operative course of treatment with Olaparib in patients with platinum sensitive relapsed ovarian cancer; the biological effects are assess in terms of the degree of PAR or PARP-1 inhibition (in tissue and ctDNA) • Germline HRD mutations and tissue mutation with respect to BRCA1/2, RAD51B, RAD51C, RAD51D, PPM1D, FANCM, BRIP1, PALB2 and BARD1 (in tissue and ctDNA) • Generate initial clinical efficacy data for future studies (RECIST 1.1) ;Main Objective: • Assess the biological effects in the primary tumour following a short pre-operative course of treatment with Olaparib in patients with platinum sensitive relapsed ovarian cancer; the biological effects are assess in terms of the degree of PAR or PARP-1 inhibition. • Evaluate germline HRD mutations and tissue mutation with respect to BRCA1/2, RAD51B, RAD51C, RAD51D, PPM1D, FANCM, BRIP1, PALB2 and BARD1 • Generate initial clinical efficacy data for future studies ;Timepoint(s) of evaluation of this end point: LVLS | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Safety and tolerability of pre-operative Olaparib (AE, SAE, SUSAR). • Response rate to olaparib in the neoadjuvant period (RECIST 1.1) • PFS and PFS2 with olaparib in comparison to platinum based chemotherapy (RECIST 1.1) • Value of ctDNA as a prognostic factor alone and in comparison to CA125 (in tissue and ctDNA) • Gene expression change in tumour tissue before and after treatment with Olaparib (in tissue and ctDNA) • Secondary mutation rate in surgical tumour specimens following PARP therapy and at progression (in tissue and ctDNA) • Changes in blood based biomarkers using ctDNA before, during and after treatment with Olaparib in an attempt to correlate with gene expression changes, BRCA mutation status and histopathological changes (in tissue and ctDNA). ;Timepoint(s) of evaluation of this end point: LVLS | — |
Countries
Belgium, Canada, Italy, United Kingdom
Contacts
Public ContactAnuska Mohaboe
SMS-oncology
Outcome results
None listed