Nivolumab With Chemotherapy in Pleural Mesothelioma After Surgery

NCT04177953 | Completed Phase 2 DMC

• 1 other identifier: NICITA
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 12

Brief 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.

Conditions

Pleural Mesothelioma Malignant

Outcome Measures

Primary Outcomes (2)

• Time-to-next-treatment (TNT) assessed according to Kaplan-Meier analysis

  Time-to-next-treatment (TNT) will be evaluated from time of randomization in order to assess efficacy of treatment, if addition of nivolumab to adjuvant chemotherapy and subsequent administration of nivolumab mono-agent as maintenance therapy will improve TNT.

  From date of randomization, every 4 weeks up to 16 months until end of treatment

• Incidence and severity of adverse events according to CTC criteria

  Incidence and severity of adverse events according to CTC criteria

  From date of randomization until 30 days after end of treatment

Secondary Outcomes (6)

• Progression-free-survival (PFS): duration from the first study drug administration to the first documented evidence of disease progression or death of any cause

  From date of randomization, every 4 weeks up to 16 months until end of treatment, and 30 days and 100 days post treatment and every 12 weeks during 32 weeks FU.

• Overall survival (OS)

  From date of randomization, every 4 weeks up to 16 months until end of treatment, and 30 days and 100 days post treatment and every 12 weeks during 32 weeks FU.

• Treatment Beyond Progression (TBP), duration of TBP in this population

  From date of randomization until date of first documented progression or date of death from any cause, whichever came first, assessed during 16 months treatment, every 4 weeks, and 30 days and 100 days post treatment, every 12 weeks during 32 weeks FU.

• Patient reported outcomes: Quality of life (QoL, based on LCSS-Meso)

  From date of Screening once and then after date of randomization every 4 weeks during treatment, up to 16 months and 30 days post treatment and every 12 weeks during 32 weeks FU.

• Patient reported outcomes: Quality of life (QoL, based on EQ-5D)

  From date of Screening once and then after date of randomization every 4 weeks during treatment, up to 16 months and 30 days post treatment and every 12 weeks during 32 weeks FU.

Study Arms (2)

Carboplatin or Cisplatin and Pemetrexed

ACTIVE COMPARATOR

Four cycles (q4w) platinum-based adjuvant chemotherapy i.v.: * carboplatin AUC5 or cisplatin 75 mg/m2 * pemetrexed 500 mg/m2

Drug: Carboplatin AUC 5; Drug: Cisplatin 75 mg/m2; Drug: Pemetrexed 500 mg/m2

Carboplatin or Cisplatin and Pemetrexed + Nivolumab

EXPERIMENTAL

Four cycles (q4w) of a combination of platinum-based adjuvant chemotherapy and immunotherapy i.v.: * carboplatin AUC5 or cisplatin 75 mg/m2 * pemetrexed 500 mg/m2 * nivolumab 480 mg flat-dose. Followed by up to 12 cycles (q4w) maintenance immunotherapy: \- nivolumab 480 mg flat-dose i.v.

Drug: Carboplatin AUC 5; Drug: Cisplatin 75 mg/m2; Drug: Pemetrexed 500 mg/m2; Biological: Nivolumab Injection

Interventions

Carboplatin AUC 5 DRUG

chemotherapy iv

Carboplatin or Cisplatin and Pemetrexed; Carboplatin or Cisplatin and Pemetrexed + Nivolumab

Cisplatin 75 mg/m2 DRUG

chemotherapy iv

Carboplatin or Cisplatin and Pemetrexed; Carboplatin or Cisplatin and Pemetrexed + Nivolumab

Pemetrexed 500 mg/m2 DRUG

chemotherapy iv

Carboplatin or Cisplatin and Pemetrexed; Carboplatin or Cisplatin and Pemetrexed + Nivolumab

Nivolumab Injection BIOLOGICAL

Human monoclonal antibody

Also known as: Opdivo

Carboplatin or Cisplatin and Pemetrexed + Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fully-informed written consent
• Males and females ≥ 18 years of age
• 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)
• 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).
• Patients must have undergone cytoreductive surgery with curative intent consisting of extended pleurectomy/decortication (eP/D) ± hyperthermic intrathoracic chemotherapy (HITOC) performed
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• 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.
• 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.
• 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.

You may not qualify if:

• Metastatic disease.
• 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.
• Previous drug therapy against MPM.
• A continuous post-operative hospitalization \> 6 weeks due to surgery-related complications.
• 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.
• Inadequate hematological, renal and hepatic functions including the following:
• WBC \< 2,000/µL
• Neutrophils \< 1,500/µL
• Platelets \< 100 x 103/µL
• Hemoglobin \<9.0 g/dL
• 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).
• AST/ALT \>3.0 x ULN
• Total bilirubin \>1.5 x ULN (except subjects with Gilbert Syndrome who must have a total bilirubin level \< 3.0 mg/dL)
• Prior organ allograft or allogeneic bone marrow transplantation.
• Concurrent or prior malignancy requiring or anticipated to require concurrent intervention.

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• Bristol-Myers Squibb: collaborator
• Thoraxklinik Heidelberg gGmbH - Universitätsklinikum Heidelberg: collaborator

Study Sites (12)

Vivantes Klinikum Neukölln, Klinik für Hämatologie, Onkologie und Palliativmedizin

Berlin, 12351, Germany

Location

Klinikum Bremen Ost Pneumologie und Beatmungsmedizin

Bremen, Germany

Location

Studienzentrum der Thorachirurgischen und Pneumologischen Klinik Klinken der Stadt Köln gGmbH Krankenhaus Merheim

Cologne, Germany

Location

Ev. Kliniken Essen-Mitte, Klinik für Internistische Onkologie

Essen, 45136, Germany

Location

Universitätsklinikum Freiburg Klinik für Innere Medizin I

Freiburg im Breisgau, Germany

Location

Asklepios Fachklinik München-Gauting Thorakale Onkologie

Gauting, Germany

Location

LungenClinic Grosshansdorf

Großhansdorf, Germany

Location

Asklepios Klinikum Harburg, Klinik für Lungen-, Thorax und Atemwegserkrankungen

Harburg, 21075, Germany

Location

Thoraxklinik Heidelberg gGmbH, Medizinische Onkologie

Heidelberg, 69126, Germany

Location

Lungenklinik Hemer, Pneumologie und Thorakale Onkologie

Hemer, 58675, Germany

Location

Universitätsklinikum Regensburg, Thoraxchirurgie

Regensburg, 95053, Germany

Location

Robert-Bosch-Krankenhaus - Klinik Schillerhöhe, Onkologie

Stuttgart, Germany

Location

Related Publications (1)

• Shah R, Klotz LV, Chung I, Feisst M, Schneider MA, Riedel J, Bischoff H, Eichhorn ME, Thomas M. A Phase II Trial of Nivolumab With Chemotherapy Followed by Maintenance Nivolumab in Patients With Pleural Mesothelioma After Surgery: The NICITA Study Protocol. Clin Lung Cancer. 2021 Mar;22(2):142-146. doi: 10.1016/j.cllc.2020.10.005. Epub 2020 Oct 14.

  PMID: 33158765 DERIVED

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

Cisplatin; Pemetrexed; Nivolumab

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Rajiv Shah, MD

  Thoraxklinik Heidelberg gGmbH, Medizinische Onkologie - Universitätsklinikum Heidelberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2019
• First Posted: November 26, 2019
• Study Start: February 4, 2019
• Primary Completion: January 30, 2025
• Study Completion: January 30, 2025
• Last Updated: February 6, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (12)