Pleural Mesothelioma MalignantPhase 2NCT04177953
Nivolumab With Chemotherapy in Pleural Mesothelioma After Surgery
A Phase 2 study testing Carboplatin AUC 5, Cisplatin 75 mg/m2 and Pemetrexed 500 mg/m2 in people with Pleural Mesothelioma Malignant, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 12 sites in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pleural Mesothelioma Malignant
- What is being tested?
- Carboplatin AUC 5, Cisplatin 75 mg/m2 and Pemetrexed 500 mg/m2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 12 sitesGermany
- Study dates
- 4 Feb 2019to 30 Jan 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Surgery conducted ≤12 weeks (≤84 days) before study inclusion and patient recovered from post-surgical complications of eP/D or eP/D + HITOC
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- 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.
Who cannot join
- 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:
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- 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.
- Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
- 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).
- 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.
- Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or compliance with the study protocol.
- Pregnant or breast-feeding women.
- 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.
- Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV).
- 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.
- 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.
- 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.
- Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.
- 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].
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Germany12 sites
Vivantes Klinikum Neukölln, Klinik für Hämatologie, Onkologie und Palliativmedizin
Berlin, 12351
Klinikum Bremen Ost Pneumologie und Beatmungsmedizin
Bremen
Studienzentrum der Thorachirurgischen und Pneumologischen Klinik Klinken der Stadt Köln gGmbH Krankenhaus Merheim
Cologne
Ev. Kliniken Essen-Mitte, Klinik für Internistische Onkologie
Essen, 45136
Universitätsklinikum Freiburg Klinik für Innere Medizin I
Freiburg im Breisgau
Asklepios Fachklinik München-Gauting Thorakale Onkologie
Gauting
LungenClinic Grosshansdorf
Großhansdorf
Asklepios Klinikum Harburg, Klinik für Lungen-, Thorax und Atemwegserkrankungen
Harburg, 21075
Thoraxklinik Heidelberg gGmbH, Medizinische Onkologie
Heidelberg, 69126
Lungenklinik Hemer, Pneumologie und Thorakale Onkologie
Hemer, 58675
Universitätsklinikum Regensburg, Thoraxchirurgie
Regensburg, 95053
Robert-Bosch-Krankenhaus - Klinik Schillerhöhe, Onkologie
Stuttgart
About this study
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.
Read the detailed description
This is a multicenter, randomized, controlled, open-label study including patients with malignant pleural mesothelioma (MPM) in tumor stages I-III who have previously undergone cytoreductive surgery by extended pleurectomy/decortication with or without hyperthermic intrathoracic chemoperfusion (eP/D ± HITOC).
Patients who have histologically proven initial diagnosis of malignant pleural mesothelioma of epithelioid subtype (including biphasic histologic subtype identified during surgery), will be included in this study. Patients must have confirmed Eastern Cooperative Group (ECOG) status 0 to 2 as well to able to be included to the study.
Patients will be centrally randomized 1:1 to receive either platinum-based adjuvant chemotherapy iv (Arm A) or platinum-based adjuvant chemotherapy iv together with nivolumab (Arm B) and stratified to (HITOC (yes vs. no)), (ECOG (0,1 vs. 2)), (Result of prior resection (macroscopic complete vs incomplete resection) with macroscopic complete resection defined as residual amounts of tumor being less than 1 cm3.
Arm A (platinum-based adjuvant chemotherapy iv) patients randomized to Arm A will receive 4 cycles (q4w) chemotherapy i.v. (carboplatin AUC5 (area under curve) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2). Usually, pemetrexed is administered first as a 10 min infusion, followed by infusion of the platinum component (starting 30 min after pemetrexed infusion). Active treatment within this arm is limited to 4 months.
Arm B (platinum-based adjuvant chemotherapy iv) patients randomized to Arm B will receive 4 cycles (q4w) chemotherapy i.v. (carboplatin AUC5 (area under curve) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2) together with up to 12 cycles (q4w) maintenance immunotherapy with nivolumab iv (480mg fixed dose over 60 minutes). During cycles 1-4, when nivolumab is administered along with chemotherapy, nivolumab will be administered as the first infusion, followed by the chemotherapy components. Subjects may be dosed with nivolumab i.v. no less than 26 days from the previous dose of drug. Active treatment within this arm is limited to 16 cycles (4 cycles adjuvant combination therapy + 12 cycles maintenance immunotherapy).
Tumor tissue, blood and stool samples will be collected for accompanying research project. (Participation is optional for participant).
During treatment, clinical visits (blood cell counts, ECG, detection of toxicity) occur prior to every treatment dose. Safety of chemotherapy/nivolumab will be monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse events (SAEs) reported.
During treatment, tumor response will be assessed by the Investigator according to modified RECIST for pleural lesions and RECIST 1.1 for non-pleural lesions (radiological imaging by CT and/or MRI of the chest and upper abdomen [including the entire liver and both adrenal glands] at 8 weeks (±7days) from the date of first drug administration, at 16 weeks (±7 days) and every 12 weeks (±7 days) thereafter, until the initiation of the next anti-cancer therapy or death. A post-End-of-Treatment anticancer therapy status (EOT and follow-up (FU)) as well as a Survival Status (follow-up (FU)) will be assessed 30 days-, 100 days- and every 12 weeks after End of Treatment (EOT).
- Conditions
- Pleural Mesothelioma Malignant
- Being tested
- Carboplatin AUC 5, Cisplatin 75 mg/m2, Pemetrexed 500 mg/m2, Nivolumab Injection
- Medical subject headings
- Mesothelioma, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Carboplatin AUC 5Drug
chemotherapy iv
Cisplatin 75 mg/m2Drug
chemotherapy iv
Pemetrexed 500 mg/m2Drug
chemotherapy iv
Nivolumab InjectionBiological
Also called Opdivo
Human monoclonal antibody
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Drug: Carboplatin AUC 5; Drug: Cisplatin 75 mg/m2; Drug: Pemetrexed 500 mg/m2; Biological: Nivolumab Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Survival rates for the different time points will be determined using the Kaplan-Meier analysis and modified RECIST for MPM
Measured: 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)
Survival rates will be assessed from randomization to death of any cause according to Kaplan-Meier analysis
Measured: 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
A descriptive analysis of the proportion of patients with Treatment Beyond Progression (TBP) as well as the duration of TBP within this population will be conducted. TBP is defined as the time of recording a tumor progression until initiation of any additional intervention against MPM due to disease progression (any systemic treatment; any locoregional measures [except for prophylactic radiotherapy to prevent procedure-track metastases]; any decision of the Investigator to switch the patient to BSC).
Measured: 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)
Questionnaires given to the patients (validated quality of life questionnaires LCSS-Meso (Lung Cancer Symptom Scale-Mesothelioma)).
LCSS-Meso contains horizontal scales from best condition (maximum value/score = better outcome) to worst condition (minimum value/score = worse outcome), containing 8 questions regarding appetite, fatigue, cough, breathlessness, pain, lung disease complaints, lung disease complaint in terms of normal activities, and today´s quality of life.
Measured: 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)
Questionnaires given to the patients (validated quality of life questionnaires EQ-5D).
EQ-5D contains questions in the field of mobility, self care, every day activities, pain, and prostration with fields to be ticked from best condition (maximum value/score = better outcome) to worst condition (minimum value/score = worse outcome). The questionnaire also contains a vertical scale of todays healthiness from 0 to 100 (0, 5, 15, 20... 95, 100). (0 = worst outcome, 100 = best outcome).
Measured: 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.
ECOG performance status
Eastern Cooperative Oncology Group patient performance status (Grading from 0 to 5)
Measured: From date of Screening once and then after date of randomization every 4 weeks during treatment, up to 16 months until End of Treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2019
- Study start4 Feb 2019
- Primary completion30 Jan 2025
- Study completion30 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pleural Mesothelioma MalignantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, University Hospital Heidelberg
- Responsible party
- Sponsor
- Investigators
- Rajiv Shah, MD, Principal investigator, Thoraxklinik Heidelberg gGmbH, Medizinische Onkologie - Universitätsklinikum Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04177953
- Sponsor's protocol ID
- NICITA
- Status last verified
- Feb 2025
- First submitted
- 11 Nov 2019
- Last updated
- 6 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No IPD will be shared.
Publications
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.
PubMed 33158765
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nivolumab With Chemotherapy in Pleural Mesothelioma After Surgery
- ClinicalTrials.gov ID
- NCT04177953
- Acronym / sponsor ID
- NICITA
- Conditions
- Pleural Mesothelioma Malignant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus NordwestUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, University Hospital Heidelberg
- Study start
- 4 Feb 2019 (actual)
- Primary completion
- 30 Jan 2025 (actual)
- Study completion
- 30 Jan 2025 (actual)
- First posted
- 26 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a multicenter, randomized, controlled, open-label study including patients with malignant pleural mesothelioma (MPM) in tumor stages I-III who have previously undergone cytoreductive surgery by extended pleurectomy/decortication with or without hyperthermic intrathoracic chemoperfusion (eP/D ± HITOC).
Patients who have histologically proven initial diagnosis of malignant pleural mesothelioma of epithelioid subtype (including biphasic histologic subtype identified during surgery), will be included in this study. Patients must have confirmed Eastern Cooperative Group (ECOG) status 0 to 2 as well to able to be included to the study.
Patients will be centrally randomized 1:1 to receive either platinum-based adjuvant chemotherapy iv (Arm A) or platinum-based adjuvant chemotherapy iv together with nivolumab (Arm B) and stratified to (HITOC (yes vs. no)), (ECOG (0,1 vs. 2)), (Result of prior resection (macroscopic complete vs incomplete resection) with macroscopic complete resection defined as residual amounts of tumor being less than 1 cm3.
Arm A (platinum-based adjuvant chemotherapy iv) patients randomized to Arm A will receive 4 cycles (q4w) chemotherapy i.v. (carboplatin AUC5 (area under curve) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2). Usually, pemetrexed is administered first as a 10 min infusion, followed by infusion of the platinum component (starting 30 min after pemetrexed infusion). Active treatment within this arm is limited to 4 months.
Arm B (platinum-based adjuvant chemotherapy iv) patients randomized to Arm B will receive 4 cycles (q4w) chemotherapy i.v. (carboplatin AUC5 (area under curve) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2) together with up to 12 cycles (q4w) maintenance immunotherapy with nivolumab iv (480mg fixed dose over 60 minutes). During cycles 1-4, when nivolumab is administered along with chemotherapy, nivolumab will be administered as the first infusion, followed by the chemotherapy components. Subjects may be dosed with nivolumab i.v. no less than 26 days from the previous dose of drug. Active treatment within this arm is limited to 16 cycles (4 cycles adjuvant combination therapy + 12 cycles maintenance immunotherapy).
Tumor tissue, blood and stool samples will be collected for accompanying research project. (Participation is optional for participant).
During treatment, clinical visits (blood cell counts, ECG, detection of toxicity) occur prior to every treatment dose. Safety of chemotherapy/nivolumab will be monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse events (SAEs) reported.
During treatment, tumor response will be assessed by the Investigator according to modified RECIST for pleural lesions and RECIST 1.1 for non-pleural lesions (radiological imaging by CT and/or MRI of the chest and upper abdomen [including the entire liver and both adrenal glands] at 8 weeks (±7days) from the date of first drug administration, at 16 weeks (±7 days) and every 12 weeks (±7 days) thereafter, until the initiation of the next anti-cancer therapy or death. A post-End-of-Treatment anticancer therapy status (EOT and follow-up (FU)) as well as a Survival Status (follow-up (FU)) will be assessed 30 days-, 100 days- and every 12 weeks after End of Treatment (EOT).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Carboplatin or Cisplatin and Pemetrexed | Active comparator | Drug: Carboplatin AUC 5, Drug: Cisplatin 75 mg/m2, Drug: Pemetrexed 500 mg/m2Four cycles (q4w) platinum-based adjuvant chemotherapy i.v.: * carboplatin AUC5 or cisplatin 75 mg/m2 * pemetrexed 500 mg/m2 |
| Carboplatin or Cisplatin and Pemetrexed + Nivolumab | Experimental | Drug: Carboplatin AUC 5, Drug: Cisplatin 75 mg/m2, Drug: Pemetrexed 500 mg/m2, Biological: Nivolumab InjectionFour 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (27 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Carboplatin AUC 5chemotherapy iv | Drug | Carboplatin or Cisplatin and Pemetrexed, Carboplatin or Cisplatin and Pemetrexed + Nivolumab |
| Cisplatin 75 mg/m2chemotherapy iv | Drug | Carboplatin or Cisplatin and Pemetrexed, Carboplatin or Cisplatin and Pemetrexed + Nivolumab |
| Pemetrexed 500 mg/m2chemotherapy iv | Drug | Carboplatin or Cisplatin and Pemetrexed, Carboplatin or Cisplatin and Pemetrexed + Nivolumab |
| Nivolumab InjectionAlso: OpdivoHuman monoclonal antibody | Biological | Carboplatin or Cisplatin and Pemetrexed + Nivolumab |
Primary outcome
Time-to-next-treatment (TNT) assessed according to Kaplan-Meier analysis
Time frame: From date of randomization, every 4 weeks up to 16 months until end of treatment
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.
Incidence and severity of adverse events according to CTC criteria
Time frame: From date of randomization until 30 days after end of treatment
Incidence and severity of adverse events according to CTC criteria
6 secondary outcomes
Progression-free-survival (PFS): duration from the first study drug administration to the first documented evidence of disease progression or death of any cause
Time frame: 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)
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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.
ECOG performance status
Time frame: From date of Screening once and then after date of randomization every 4 weeks during treatment, up to 16 months until End of Treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2025.
- Derived from this study: PubMed 33158765Shah 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.
- Individual participant dataSharing planned: No. No IPD will be shared.
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Advanced Solid Tumor, Mesothelioma, Malignant
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rajiv Shah, MD principal investigator
Thoraxklinik Heidelberg gGmbH, Medizinische Onkologie - Universitätsklinikum Heidelberg
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carboplatin AUC 5, Cisplatin 75 mg/m2 and Pemetrexed 500 mg/m2 in people with Pleural Mesothelioma Malignant, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 12 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time-to-next-treatment (TNT) assessed according to Kaplan-Meier analysis (time frame: From date of randomization, every 4 weeks up to 16 months until end of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04177953, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2025.