Nivolumab With Chemotherapy in Pleural Mesothelioma After Surgery

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Patients with malignant pleural mesothelioma stage I-III who have undergone cytoreductive surgery with curative intend consisting of extended pleurectomy / decortication (eP/D) with or without hyperthermic intrathoracic chemoperfusion (HITOC) who will receive a maximum treatment duration of 16 cycles (4 cycles of chemotherapy in both arms + 12 cycles maintenance immunotherapy in treatment arm B). The main objective of the trial is Time-to-next-treatment (TNT), as well as safety and tolerability.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: IKF Klinische Krebsforschung GmbH at Krankenhaus Nordwest; Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
• Collaborator: Bristol-Myers Squibb
• Treatments: Carboplatin; Cisplatin; Nivolumab; Pemetrexed

Criteria

Inclusion Criteria:

1. Fully-informed written consent

2. Males and females ≥ 18 years of age

3. Histologically proven initial diagnosis of malignant pleural mesothelioma of epithelioid subtype (patients can also be included if biphasic histologic subtype has been identified during surgery)

4. Postoperative stage I-III (TNM 8th Edition; pT1-4, pN0-2, cM0). Patients are only included with a completeness of cytoreduction score (CC score) <3 (i.e., residual tumor thickness ≤2.5 cm).

5. Patients must have undergone cytoreductive surgery with curative intent consisting of extended pleurectomy/decortication (eP/D) ± hyperthermic intrathoracic chemotherapy (HITOC) performed

6. Surgery conducted ≤12 weeks (≤84 days) before study inclusion and patient recovered from post-surgical complications of eP/D or eP/D + HITOC

7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

8. Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial. Women must not be breastfeeding.

9. The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.

10. WOCBP must agree to follow instructions for method(s) of contraception for a period of 30 days (duration of ovulatory cycle) plus the time required for the investigational drug to undergo 5 half-lives. The terminal half-lives of nivolumab is approximately 25 days. WOCBP should use an adequate method to avoid pregnancy for approximately 5 months (30 days plus the time required for nivolumab to undergo 5 half-lives) after the last dose of investigational drug. Females must agree to refrain from egg donating (ova, oocytes) during the intervention period and for at least 5 months after last dose of study intervention.

Exclusion Criteria:

1. Metastatic disease.

2. Patients for which surgery was scheduled as a cytoreductive surgery with curative intent but was then defined as palliative P/D by the operating surgeon.

3. Previous drug therapy against MPM.

4. Post-operative hospitalization > 6 weeks.

5. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways.

6. Inadequate hematological, renal and hepatic functions including the following:

1. WBC < 2,000/µL

2. Neutrophils < 1,500/µL

3. Platelets < 100 x 103/µL

4. Hemoglobin <9.0 g/dL

5. Serum creatinine >1.5 x ULN unless creatinine clearance ≥ 45 mL/min (measured or calculated using the Cockcroft-Gault formula). For application of cisplatin, creatinine clearance must be ≥ 60 mL/min. (measured or calculated using the Cockcroft-Gault formula).

6. AST/ALT >3.0 x ULN

7. Total bilirubin >1.5 x ULN (except subjects with Gilbert Syndrome who must have a total bilirubin level < 3.0 mg/dL)

7. Prior organ allograft or allogeneic bone marrow transplantation.

8. Concurrent or prior malignancy requiring or anticipated to require concurrent intervention.

9. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.

10. Malignancies other than disease under study within 3 years prior to inclusion, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS > 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent).

11. 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 subject to receive study drug.

12. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or compliance with the study protocol.

13. Pregnant or breast-feeding women.

14. Positive testing for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.

15. Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV).

16. Subjects with active, known, or suspected autoimmune disease. Subjects with Type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll. For any cases of uncertainty, it is recommended that the medical monitor be consulted prior to signing informed consent.

17. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

18. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.

19. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.

20. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].