Unresectable mesothelioma Cancer Mesothelioma
Conditions
Interventions
Mesothelioma patients with any histological subtype (epithelioid or non-epithelioid) and any site (pleural or peritoneal) who have previously received an approved systemic therapy containing platinum,
Sponsors
University Hospital Southampton NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
18 Years to 120 Years
Inclusion criteria
Inclusion criteria: 1. Patients must have signed and dated a REC-approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care 2. Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study. 3. Histologically confirmed diagnosis of mesothelioma. Any histological subtype (epithelioid, biphasic or sarcomatoid) and any site (e.g. pleural or peritoneal) with an available tissue block. Tissue blocks will be requested at the time of screening 4. Patients must have received prior systemic therapy (any number of lines) for pleural or peritoneal mesothelioma 5. Disease progression must be confirmed per Investigator's assessment prior to screening 6. Any prior treatment must be completed at least 14 days prior to receiving study treatment, with no ongoing toxicity of CTCAE Grade 3 or above. 7. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1 (see appendix 1) 8. Radiologically assessable disease by modified RECIST (pleural mesothelioma) or RECIST 1.1 (non-pleural mesothelioma or where measurements for modified RECIST cannot be obtained) 9. Age =18 years old 10. Consent to provide mandatory diagnostic tissue blocks and blood samples for translational research, including an optional rebiopsy at progression 11. Adequate organ function, including suitable bone marrow reserve and creatinine clearance 12. Screening laboratory values must meet the following criteria within 48 hours prior to commencement of treatment: 12.1. White blood cells =2 x 10e9/l 12.2. Neutrophils =1.5 x 10e9/l 12.3. Platelets =100 x 10e9/l 12.4. Haemoglobin =90 g/l 12.5. Serum creatinine of =1.5 X ULN or creatinine clearance (CrCl) >50 ml/minute (using Cockcroft/Gault formula) 12.5.1. Female CrCl= [(140 - age in years) x weight in kg x 0.85) ÷ (72 x serum creatinine in µmol/l)] 12.5.2. Male CrCl= [(140 - age in years) x weight in kg x 1.00) ÷ (72 x serum creatinine in µmol/l)] 12.6. AST =3 x ULN OR ALT =3 x ULN (if both are assessed, both need to be =3 x ULN) 12.7. Total bilirubin =1.5 x ULN (except patients with Gilbert Syndrome, who must have total bilirubin <51.3 µmol/l) 13. Reproductive status (refer to section 4.6) 13.1. Women of childbearing potential (WOCBP, as defined in section 4.6) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) at enrolment and within 24 hours prior to the start of study treatment. An extension up to 3 days prior to the start of study treatment may be permissible in situations where results cannot be obtained within a 24-hour window. 13.2. Women must not be breastfeeding 13.3. WOCBP must agree to use a highly effective method of contraception (as outlined in section 4.6) for the duration of treatment and 180 days after the last dose of ASC+ niraparib 13.4. Men who are sexually active with WOCBP must use the contraceptive methods as outlined in section 4.6 for the duration of treatment and for 90 days after the last dose of ASC+ niraparib 14. Expected survival of at least 12 weeks per Investigator's assessment
Exclusion criteria
Exclusion criteria: 1. Patients with untreated, symptomatic central nervous system (CNS) metastases are excluded, including carcinomatous meningitis, leptomeningeal disease, and radiographic signs of CNS haemorrhage are excluded 2. Patients with untreated third space fluid collection requiring therapeutic drainage are excluded 3. Second malignancy within 5 years except cancers with definitely treated with curative intent (eg. basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ bladder or in situ cervical cancer) 4. Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the patient to receive protocol therapy 5. Difficulty swallowing or previous significant resection of the stomach or small bowel 6. Patients who have not recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment 7. Prior exposure to PARP Inhibitor or known hypersensitivity to the components of niraparib 8. New York Heart associated class II or greater heart failure, hepatic [AST > 3 x ULN, ALT >3 x ULN Total bilirubin >1.5 x ULN] or renal impairment [serum creatinine of >1.5 x ULN or creatinine clearance (CrCl) =50 ml/minute (using Cockcroft/Gault formula)] 9. Known alcohol or drug abuse 10. Patients are not permitted to enter any other interventional studies 11. Any patient not able to give consent 12. Any pregnant or breastfeeding patient 13. Patient with known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML) 14. Patient with known history of active tuberculosis 15. Patients with uncontrolled hypertension 16. Participants have current pneumonitis within 90 days of the planned start of the study or a known history of interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis requiring steroid treatment 17. Patients that have received colony-stimulating factors (e.g., granulocyte-macrophage colony-stimulating factor or recombinant erythropoietin) within 2 weeks prior to the first dose of study treatment 18. Live vaccines within 30 days prior to the first dose of study treatment and while participating in this clinical study 19. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) 20. Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival determined by modified Response Evaluation Criteria in Solid Tumours (RECIST) (pleural disease), RECIST 1.1 (for non-pleural disease) or investigator reported progression. RECIST will be assessed every 6 weeks from randomisation until disease progression or end of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Measured until disease progression or death (unless otherwise specified): 1. Overall survival defined as the time from randomisation to death from any cause 2. Best overall response (progressive disease, stable disease, partial or complete response) assessed by modified RECIST or RECIST 1.1. The best overall response is the best response recorded from the start of treatment until disease progression or death. 3. ORR (assessed by modified RECIST or RECIST 1.1), the percentage of patients whose best overall response is partial or complete response 4. Disease control at 12 and 24 weeks (stable disease, partial or complete response) assessed by modified RECIST or RECIST 1.1 at 12 and 24 weeks 5. Duration of response, defined as the time from complete or partial response (where this occurs) until progression or death 6. Treatment compliance assessed by summarising the percentage of the received dose relative to the intended dose at each cycle 7. Toxicity assessed through evaluation of adverse events (graded using Common Terminology Criteria for Adverse Events [CTCAE] v5.0), laboratory results, vital signs and physical examination at baseline, after each treatment cycle, and for 100 days post treatment discontinuation and for ongoing drug-related AEs until resolved, return to baseline, or deemed irreversible | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Contacts
Public ContactDaniel Griffiths
Outcome results
None listed