TALAMESO : A Three-Cohort Phase II trial to Assess the Efficacy of a Maintenance Treatment with TALAzoparib following First Line Platinum-based Chemotherapy in Pleural or Malignant Peritoneal MESOthelioma Patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospices Civils De Lyon

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

4 Nov 2020 → ongoing

Decision date (initial)

2024-08-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

PFIZER

External identifiers

EU CT number

2024-514104-14-00

EudraCT number

2019-004388-37

ClinicalTrials.gov

NCT04462809

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To assess the efficacy, assessed by the proportion of patients who are free of progression 6 months after starting talazoparib maintenance treatment, that will follow minimum 4 cycles of systemic platinum-based first line chemotherapy, in patients with advanced malignant pleural (cohort A) or peritoneal mesothelioma (cohorts B1 and B2).

Secondary objectives 5

1. To assess other efficacy parameters, and survivals
2. To assess the safety
3. Translationnal research objectives : To identifying predictive biomarkers of response to talazoparib
4. Translationnal research objectives : To characterize genes involved in homologous recombination DNA repair pathway
5. Translationnal research objectives : To sequence BAP1 gene and assess its protein expression by immunohistochemistry

Conditions and MedDRA coding

Adults subjects with advanced malignant pleural (cohort A) or peritoneal (cohorts B1 and B2) mesothelioma.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Patients older than 18 years old
2. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
3. Histologically - or cytologically- confirmed malignant mesotheliomas: epithelioid, sarcomatoid, biphasic - Developed from pleura (cohort A) or from peritoneum (cohorts B1 and B2) - Previously treated with systemic platinum based-chemotherapy (including minimum one cycle of pemetrexed) for minimum 4 cycles, with no sign of disease progression during chemotherapy
4. No previous treatment with bevacizumab and PARP inhibitor
5. Minimum 6 weeks and maximum 8 weeks interval between last chemotherapy cycle and talazoparib start OR minimum 6 and maximum 8 weeks after cytoreductive surgery performed after neo-adjuvant treatment (including the necessary number of cycles of platinum-pemetrexed for inclusion) in the absence of adjuvant chemotherapy. - For pleural mesotheliomas (cohort A), primary or interval debulking surgery with or without hyperthermic intrapleural or intrathoracic chemotherapy (HITHOC) will be authorized, in the case of non-complete cytoreductive surgery only - For peritoneal mesotheliomas * In cohort B1, primary or interval debulking surgery ± hyperthermic intraperitoneal chemotherapy (HIPEC) will be authorized in the case of non-complete cytoreductive surgery (CC2 or CC3) only. This cohort will also include patients with non-operated diseases. Intraperitoneal treatments with pressurized intraperitoneal aerosol chemotherapy sessions (PIPAC) are allowed only with systemic chemotherapy for this cohort. * In cohort B2, complete macroscopic (CC0 or CC1) primary or interval debulking surgery ± HIPEC will be required. Intraperitoneal treatments with pressurized intraperitoneal aerosol chemotherapy sessions (PIPAC) are allowed in neoadjuvant chemotherapy treatment prior to surgery. **In all cohorts, HITHOC, HIPEC and PIPAC are NOT considered as systemic platinum-based chemotherapy
6. Measurable or non-measurable (but radiologically evaluable) disease as per modified RECIST version 1.1 on computed tomography (CT) scan (within 28 days prior to talazoparib initiation), or for cohort B2, authorization of absence of radiological lesion
7. Availability at the study site of a representative Formalin-Fixed Paraffin-Embedded (FFPE) tumor sample in a block if possible or at least 30 unstained slides from biopsy or surgery specimen, aged less than 18 months.
8. Patients with adequate bone marrow function measured within 28 days prior to administration of study treatment as defined below: o Absolute neutrophil count ≥1.0 x 109 /L o Platelet count ≥50 x 109 /L o Haemoglobin ≥8.0 g/dL (may have been blood transfused)
9. Patients with adequate renal function: o Calculated Glomerular Filtration Rate ≥30 ml/min/1.73 m2 according to CKD-EPI formula
10. Patients with adequate hepatic function: o Total bilirubin ≤ 1.5 × upper limit of normal [ULN] o ASAT/ALAT ≤1.5 × ULN
11. Patients must have a life expectancy ≥ 16 weeks.
12. Confirmation of non-childbearing status (pregnancy test) for women of childbearing potential.
13. A highly effective method of contraception is required for female patients during treatment of talazoparib, and for at least 7 months after completing therapy. Advise male patients with female partners of reproductive potential and pregnant partners to use a condom, during treatment with talazoparib and for at least 4 months after the final dose
14. Patients who gave its written informed consent to participate to the study.
15. Patients affiliated to a social insurance regime.
16. Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Exclusion criteria 16

1. Uncontrolled intercurrent illness, including but not limited to, such as congestive heart failure; respiratory distress; liver failure; allergy, or psychiatric illness/social situations that would limit compliance with study requirement according to the investigator, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
2. In cohorts B1 and B2: Patients with tumor recurrence within 9 months of the last cycle of previous platinum-based chemotherapy line
3. Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years.
4. All subjects with brain metastases or meningeal involvement.
5. Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 6 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment with study drug.
6. Persistent toxicities (CTCAE ≥ grade 2) with the exception of alopecia and sensory neuropathy, caused by previous cancer therapy.
7. Treatment with other investigational agents.
8. Bowel occlusive syndrome, inflammatory bowel disease, immune colitis, or other gastro-intestinal disorder that does not allow oral medication such as malabsorption.
9. Known severe hypersensitivity reactions to PARP inhibitors.
10. Known HIV or AIDS related illness.
11. Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive).
12. Treatment with oral anticoagulant anti-vitamin K such Coumadin®.
13. Prior organ transplantation, including allogeneic stem cell transplantation (excluding autologous bone marrow transplant).
14. Patients under guardianship.
15. Women who are breastfeeding (during treatment with talazoparib and for at least 1 month after the final dose).
16. Participation in other interventional clinical research that may interfere with the experimental drugs efficacy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Non-progression proportion 6 months after starting talazoparib in TALAMESO trial.

Secondary endpoints 7

1. Related to progression free-survival based on RECIST 1.1 criteria (only for Malignant Peritoneal Mesothelioma)
2. Related to progression free-survival based on mRECIST criteria (For Malignant Peritoneal Mesothelioma and Malignant Pleural Mesothelioma)
3. Related to overall survival
4. Related to safety
5. Translational endpoints : On FFPE (paraffin embedded archival blocks) pretreatment tumor samples : BAP1 and HR genes status
6. Translational endpoints : On FFPE (paraffin embedded archival blocks) pretreatment tumor samples : RAD51 foci assay
7. Translational endpoints : On FFPE (paraffin embedded archival blocks) pretreatment tumor samples : HRD transcriptomic signature

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospices Civils De Lyon

Sponsor organisation

Hospices Civils De Lyon

Address

3 Quai Des Celestins, Bp 2251 Bp 2251

City

Lyon Cedex 02

Postcode

69229

Country

France

Scientific contact point

Organisation

Hospices Civils De Lyon

Contact name

Pr YOU

Public contact point

Organisation

Hospices Civils De Lyon

Contact name

Pr YOU

Locations

1 EU/EEA country · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications