Nivolumab With Chemotherapy in Pleural Mesothelioma After Surgery
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|ClinicalTrials.gov Identifier: NCT04177953|
Recruitment Status : Recruiting
First Posted : November 26, 2019
Last Update Posted : February 18, 2021
|Condition or disease||Intervention/treatment||Phase|
|Pleural Mesothelioma Malignant||Drug: Carboplatin AUC 5 Drug: Cisplatin 75 mg/m2 Drug: Pemetrexed 500 mg/m2 Biological: Nivolumab Injection||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||92 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Nivolumab With Chemotherapy in Pleural Mesothelioma After Surgery|
|Actual Study Start Date :||February 4, 2019|
|Estimated Primary Completion Date :||July 2023|
|Estimated Study Completion Date :||December 2023|
Active Comparator: Carboplatin or Cisplatin and Pemetrexed
Four cycles (q4w) platinum-based adjuvant chemotherapy i.v.:
Drug: Carboplatin AUC 5
Drug: Cisplatin 75 mg/m2
Drug: Pemetrexed 500 mg/m2
Experimental: Carboplatin or Cisplatin and Pemetrexed + Nivolumab
Four cycles (q4w) of a combination of platinum-based adjuvant chemotherapy and immunotherapy i.v.:
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
Human monoclonal antibody
Other Name: Opdivo
- 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
- 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. ]Survival rates for the different time points will be determined using the Kaplan-Meier analysis and modified RECIST for MPM
- 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. ]Survival rates will be assessed from randomization to death of any cause according to Kaplan-Meier analysis
- 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. ]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).
- 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. ]
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.
- 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. ]
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).
- 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 ]Eastern Cooperative Oncology Group patient performance status (Grading from 0 to 5)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04177953
|Contact: Rajiv Shah, MD||+49 6221 396 ext firstname.lastname@example.org|
|Contact: Johanna Riedel, PhD||+49 69 7601 ext email@example.com|
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