NCT05255471Phase 3Recruiting
National Cancer Institute, Naples · IRCCS Istituto Nazionale Tumori di Napoli, Naples
MITO 35b is designed as randomized, open label, phase III trial that aims to assess the efficacy of olaparib maintenance beyond progression compered to standard platinum-based chemotherapy after secondary cytoreductive surgery.
The target population of this study are ovarian cancer patients who experience a disease recurrence or progression to a first line maintenance therapy with PARPi; at progression patients must have received a secondary cytoreduction according to clinical practice.
Eligibility: 18 Years to · Female · * Signed informed consent prior to any study specific procedures;
* Female, age ≥ 18 years at time of signing informed consent
* Patients with high-grade serous or endometroid ovarian, fallopian tube, or primary peritoneal cancer recurrent or progressive after first line PARPi maintenance are allowed;
* Patients must have received only one previous line of a platinum containing regimen not containing bevacizumab;
* Patient must have received a first-line maintenance therapy with a PARPi for at least 6 months, if the prior PARPi used was olaparib then patients must have received treatment without significant toxicity or the need for a permanent dose reduction.Patients who experience disease relapse after the end of the 24 months maintenance therapy are eligible;
* Patients must have undergone secondary cytoreductive surgery. The cytoreduction must result in complete resection (absence of macroscopic residual tumor) or at least resection of the progressive lesion(s) occurring during maintenance;
* Documented BRCA1/2 status. Both mutated and wild type patients are eligible. Patient with unknown status of BRCA genes agrees to undergo analysis of their germline and somatic BRCA status (testing must be completed prior to enrolment in the study);
* Patients must have a life expectancy ≥ 16 weeks;
* Patients must start the experimental treatments in the current study within 3 to 8 weeks from second surgery;
* ECOG performance status 0 to 1;
* Patient must provide archival tumor samples formalin fixed, paraffin embedded (FFPE) from both the primary and secondary surgeries for paired analysis. A quality control analysis of samples will be performed before patient's randomization;
* Patient must be able to take oral medications;
* Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
* Haemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days
* Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
* Platelet count ≥ 100 x 109/L
* Total serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) and Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x ULN for the institution (or ≤ 5x ULN if liver metastases are present)
* Patients must have creatinine clearance estimated of ≥51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test: Estimated creatinine clearance = (140-age \[years\]) x weight (kg) (x F)a serum creatinine (mg/dL) x 72 (a where F=0.85 for females.
* 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 Cycle 1. Postmenopausal is defined as:
* Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50;
* radiation-induced oophorectomy with last menses \>1 year ago;
* chemotherapy-induced menopause with \>1-year interval since last menses;
* surgical sterilisation (bilateral oophorectomy or hysterectomy).
* Women of childbearing potential and their partners, who are sexually active, must agree to the use of one highly effective forms of contraception and their partners must use a male condom, during the treatment and for at least 1 months after last dose of olaparib.For chemotherapy drugs, please refer to fertility section of corresponding Summary of Product Characteristics (SCP);
* Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures;
NCT05378204NARecruiting
Institut Claudius Regaud · Institut Bergonie, Bordeaux
The purpose of this study is to assess whether expression of not only POLQ/Polθ, but also Shieldin complex and/or 53BP1 are correlated with primary and/or acquired resistance to PARPi (Poly(ADP-Ribose) Polymerases inhibitors) in a sub-population of locally advanced or metastatic breast cancer patients and vary regarding type and location of gBRCA1/2 mutations.
This translational research program is composed of two multicentric, non-randomized prospective studies in patients with HER2-negative locally advanced or metastatic breast cancer:
* The main study concerns 80 patients eligible for PARPi (according to the investigators).PARPi treatments (talazoparib or olaparib) will be administered and dosed according to the standard of care administration.
* The sub-study concerns 40 patients in progression disease under PARPi alone.
For each included patient in the main study or sub-study, tumor biopsy specimen and blood samples will be collected at different times during the study.
Eligibility: 18 Years to · All · MAIN STUDY
INCLUSION CRITERIA:
1. Women (or men) aged ≥ 18 years with histologically proven breast cancer
2. Metastatic relapse or locally advanced breast cancer
3. No-HER2 overexpression or amplification
4. Triple-negative (defines as ER\<1%, PR\<1% and HER2-negative as per ASCO CAP guidelines) or hormone receptor positive (defines as ER and/or PR ≥ 1%) breast cancer
5. Patients with metastases that can be biopsied except bone metastases. At baseline, if patients already have an archived biopsy from a secondary or a primary site (if stage IV) of their current disease, this material can be used for the study, provided that, it was collected within 3 months prior enrollment and a frozen and a FFPE sample are both available for research
6. ECOG Performance Status ≤ 2
7. Patients must have measurable or evaluable disease according to RECIST v1.1
8. Patient with deleterious germline BRCA 1 and/or 2 mutation, eligible for PARP inhibitor therapy (olaparib or talazoparib), according each investigator
9. Any number of prior lines therapy are allowed
10. Current treatment with PARP inhibitor not yet started
11. Women should be post-menopaused or willing to accept the use of an effective contraceptive regimen during the treatment period by PARP inhibitor
12. Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol
13. Patient affiliated to a Social Health Insurance in France
NON-INCLUSION CRITERIA:
1. Abnormal coagulation contraindicating biopsy
2. Bone metastases when this is the only site of biopsiable disease
3. Patients with all target in a previously irradiated region, except if clear progression has been observed prior to study in at least one of them
4. Patients with known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
5. Patients with known untreated CNS metastases and/or carcinomatous meningitis
6. Patients with a known history of Human Immunodeficiency Virus (HIV)
7. Patients with known active Hepatitis B or C
8. Patients should not be on any other anti-cancer therapy (chemotherapy, endocrine therapy, immunotherapy, tailored therapy or alternative investigational therapy)
9. Patient pregnant, or breast-feeding
10. Any psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the provision of informed consent or compliance to study procedure
11. Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice)
SUB-STUDY
INCLUSION CRITERIA:
1. Women (or men) aged ≥ 18 years with histologically proven breast cancer
2. Metastatic relapse or locally advanced breast cancer
3. No-HER2 overexpression or amplification
4. Triple-negative (defines as ER\<1%, PR\<1% and HER2-negative as per ASCO CAP guidelines) or hormone receptor positive (defines as ER and or PR ≥ 1%) breast cancer
5. Patients with metastases that can be biopsied except bone metastases
6. ECOG Performance Status ≤ 2
7. Patients, with deleterious germline BRCA 1 and/or 2, in progression under PARPi alone (talazoparib or olaparib)
8. Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol
9. Patient affiliated to a Social Health Insurance in France
NON-INCLUSION CRITERIA:
1. Abnormal coagulation contraindicating biopsy
2. Bone metastases when this is the only site of biopsiable disease
3. Patient pregnant, or breast-feeding
4. Patients with a known history of Human Immunodeficiency Virus (HIV)
5. Patients with known active Hepatitis B or C
6. Any psychological, familial, geographic or social situation, according to the judgment
