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Nivolumab Monotherapy or Nivolumab Plus Ipilimumab, for Unresectable Malignant Pleural Mesothelioma (MPM) Patients (MAPS2)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02716272
First Posted: March 23, 2016
Last Update Posted: September 20, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Intergroupe Francophone de Cancerologie Thoracique
  Purpose
The sponsor raise the hypothesis that inhibition of immune PD-1+/- CTLA-4 check-point(s) would delay tumor progression in patients with unresectable MPM, experiencing disease progression after one or two lines of chemotherapy including at least first-line with pemetrexed and platinum, without altering significantly the quality of life of patients.

Condition Intervention Phase
Mesothelioma Drug: Nivolumab Drug: Nivolumab + Ipilimumab Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study Evaluating Efficacy and Safety of 2nd or 3rd Line Treatment by Nivolumab Monotherapy or Nivolumab Plus Ipilimumab, for Unresectable Malignant Pleural Mesothelioma (MPM) Patients

Resource links provided by NLM:


Further study details as provided by Intergroupe Francophone de Cancerologie Thoracique:

Primary Outcome Measures:
  • Disease Control rate assessed by CT scan [ Time Frame: 3-months ]
    Tumor assessment (modified RECIST1.0 for mesothelioma)


Secondary Outcome Measures:
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 3-months ]
    NCI CTC AE 4.0

  • Progression-Free Survival [ Time Frame: 3-month ]
  • Overall Survival [ Time Frame: 3-months ]
  • Quality of Life [ Time Frame: 3-months ]
    LCSS ( Lawrence County School System) Scale

  • prognosis impact of blood biomarkers (exploratory studies) [ Time Frame: 3-months ]
    dosage in blood of numerous biomarkers and analysis of their prognosis impact


Enrollment: 125
Study Start Date: April 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MONOTHERAPY ARM
Nivolumab administered IV over 60 minutes at 3mg/kg every 2 weeks
Drug: Nivolumab
Nivolumab administered IV over 60 minutes at 3mg/kg every 2 weeks
Experimental: COMBINATION ARM
Nivolumab administered IV over 60 minutes at 3mg/kg every 2 weeks, combined with Ipilimumab administered IV over 90 minutes at 1mg/Kg every 6 weeks
Drug: Nivolumab + Ipilimumab
Nivolumab administered IV over 60 minutes at 3mg/kg every 2 weeks, combined with Ipilimumab administered IV over 90 minutes at 1mg/Kg every 6 weeks

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically proved diagnosis of unresectable malignant pleural Mesothelioma (MPM)
  2. Available (archival and/or fresh) pathological samples for centralized PD-L1 expression assessment by immunohistochemistry
  3. Age ≥ 18 years old; male and female
  4. ECOG Performance status 0-1
  5. Weight loss < 10% during last 3 months
  6. Life expectancy > 12 weeks
  7. Documented progression of the MPM, assessed by computed tomography (CT) -Scan.
  8. Measurable disease, defined as at least 1 lesion (measurable) that can be accurately assessed at baseline by CT-Scan and is suitable for repeated assessment using modified Response Evaluation Criteria in Solid Tumors [RECIST] for pleural mesothelioma (Byrne 2004; Therasse 2006).
  9. Previous treatment by 1 or 2 systemic chemotherapy lines (1 line of chemotherapy considered if the patient received ≥2 cycles of this chemotherapy), including at least one line with pemetrexed in combination with platinum agent (i.e. "gold standard chemotherapy in MPM; triplet including bevacizumab also accepted)
  10. Written informed consent
  11. Patients must have adequate organ function : creatinine clearance > 50 mL/min (Cockcroft formula), Neutrophiles count > 1500/mm3; Platelets > 100 000/mm3 ; Hemoglobin > 9 g/dL; hepatic enzymes < 3N with total bilirubin ≤ 1.5 × ULN (upper limit of normal) except subjects with documented Gilbert's syndrome (≤ 5 × ULN) or liver metastasis, who must have a baseline total bilirubin ≤ 3.0 mg/dL
  12. Recovered from all toxicities associated with prior treatment, to acceptable baseline status, or a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.0) Grade of 0 or 1, except for toxicities not considered a safety risk, such as alopecia or vitiligo
  13. Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception for 28 days prior to the first dose of investigational product, and must agree to continue using such precautions for 6 months after the final dose of investigational product; cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. They must also refrain from egg cell donation for 6 months after the final dose of investigational product. Men receiving nivolumab and who are sexually active with women of childbearing potential will be instructed to adhere to contraception for a period of 31 weeks after the last dose of nivolumab.

Exclusion Criteria:

  1. Patients with primitive peritoneal, pericardial, testis or tunica vaginalis mesothelioma
  2. Patients with a recent history of other malignancies except adequately treated non-melanoma skin cancer, and curatively treated in-situ cancer. Patients with prostate adenocarcinoma diagnosed less than 5 years could be included in case of localized prostate cancer with good outcome according the Amico classification: ≤ T2a and Gleason Score ≤6 and PSA blood level ≤10 ng/ml, and treated with curative intent (surgery or radiotherapy) without chemotherapy. Patients with history of solid tumors, including adenocarcinoma, treated with curative intent and without any evidence of disease >5 years can be included as well.
  3. Brain metastasis, except if surgically resected or treated with stereotaxic radiotherapy with no evolution within the 3 months before inclusion, and asymptomatic patient
  4. History of primary immunodeficiency, history of organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of randomization or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy.
  5. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Intranasal/inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
  6. Live attenuated vaccination administered within 30 days prior to randomization.
  7. Known history of interstitial lung disease (asbestosis…) or CT-scan signs of interstitial lung disease.
  8. Subjects with an active, known or suspected autoimmune disease, including systemic lupus erythematosis or Wegener's granulomatosis. Subjects with type I diabetes mellitis, or hypothyroidism only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, are permitted to enroll.
  9. Active or history of inflammatory bowel disease (eg, diverticulitis, colitis, Crohn's), irritable bowel disease, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea. Note that diverticulosis is permitted.
  10. Patients with active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol. This includes but is not limited to:

    • known prior history of active tuberculosis-disease;
    • known acute or chronic B or C hepatitis by serological evaluation. Patients with serological sequelae of hepatitis (antibodies test serologically positive for virus) without hepatitis could be included.
    • known Human immunodeficiency virus infection.
  11. 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
  12. The last dose of prior chemotherapy or radiation therapy (with the exception of palliative radiotherapy) was received less than 3 weeks prior to randomization
  Contacts and Locations
Information from the National Library of Medicine

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): NCT02716272


Locations
France
Angers - CHU
Angers, France, 49000
Avignon - Institut Sainte-Catherine
Avignon, France, 84918
CHU
Clermont-Ferrand, France
Dijon - CHU
Dijon, France, 63000
Grenoble - CHU
Grenoble, France, 38000
Centre Hospitalier - Pneumologie
Le Havre, France, 76600
Centre Hospitalier - Pneumologie
Le Mans, France, 72000
CHRU Lille - Hopital Calmette
Lille, France
AP-HM Hôpital Nord
Marseille, France
Mulhouse - CH
Mulhouse, France, 68000
AP-HP Hopital Tenon - Pneumologie
Paris, France, 75020
AP-HP Hôpital Bichat
Paris, France
HCL Lyon Sud
Pierre Bénite, France, 69495
Pontoise - CH
Pontoise, France
Rennes - CHU
Rennes, France
Rouen - CHU
Rouen, France, 76000
Centre Etienne Dolet
Saint-Nazaire, France
CHU Strasbourg
Strasbourg, France
Toulon - CHI
Toulon, France, 83000
Toulouse - CHU Larrey
Toulouse, France
CHU Tours - Pneumologie
Tours, France
Gustave Roussy
Villejuif, France, 94800
Sponsors and Collaborators
Intergroupe Francophone de Cancerologie Thoracique
Investigators
Principal Investigator: Arnaud Scherpereel, MD, PhD IFCT
Principal Investigator: Gérard Zalcman, MD, PhD IFCT
  More Information

Additional Information:
Responsible Party: Intergroupe Francophone de Cancerologie Thoracique
ClinicalTrials.gov Identifier: NCT02716272     History of Changes
Other Study ID Numbers: IFCT-1501
First Submitted: March 9, 2016
First Posted: March 23, 2016
Last Update Posted: September 20, 2017
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Intergroupe Francophone de Cancerologie Thoracique:
mesothelioma
immunotherapy
nivolumab
ipilimumab

Additional relevant MeSH terms:
Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs