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Trial record 1 of 3 for:    18506025 [PUBMED-IDS]
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Optimal Sequencing of Pembrolizumab (MK-3475) and Standard Platinum-based Chemotherapy in First-Line NSCLC

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ClinicalTrials.gov Identifier: NCT02591615
Recruitment Status : Recruiting
First Posted : October 29, 2015
Last Update Posted : May 19, 2017
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Alliance Foundation Trials, LLC.

Brief Summary:
This is a multicenter randomized phase II to determine if the administration of standard platinum-based chemotherapy before MK-3475 in with Chemotherapy naive stage IV Non-small Cell Lung Cancer (NSCLC) will improve the overall response rate (ORR) compared to MK-3475 administered before chemotherapy. Patients will be given Pembrolizumab as maintenance up to 1 year: Carboplatin and paclitaxel or pemetrexed every 3 weeks x 4 cycles followed by pembrolizumab every 3 weeks for up to 1 year. Pembrolizumab every 3 weeks x 4 cycles followed by carboplatin and paclitaxel or pemetrexed every 3 weeks x 4 cycles followed by pembrolizumab every 3 weeks for up to 1 year.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: MK-3475 Drug: Carboplatin Drug: Paclitaxel Drug: Pemetrexed Phase 2

Detailed Description:
While a genotype-directed strategy has been established as effective in treatment selection for patients with advanced NSCLC, only a minority of patients at this time will have a readily identifiable actionable molecular target. Furthermore, genotype-directed therapy has not been validated for patients with squamous cell carcinoma of the lung. Therefore, the majority of patients with advanced NSCLC will continue to rely on standard platinum-based doublet chemotherapy. Given the plateau in effectiveness of this approach, novel treatment strategies are clearly warranted.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial Evaluating the Optimal Sequencing of PD-1 Inhibition With Pembrolizumab (MK-3475) and Standard Platinum-based Chemotherapy in Patients With Chemotherapy Naive Stage IV Non-small Cell Lung Cancer
Study Start Date : March 2016
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Arm A

For Squamous Carcinoma Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles Paclitaxel 200 mg/m2 IV day 1 every 21-days for up to 4 cycles

OR

For Non-squamous Carcinoma Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles

Drug: Carboplatin
Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Other Names:
  • Paraplat
  • Paraplatin
Drug: Paclitaxel
Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Other Name: Taxol
Drug: Pemetrexed
Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Other Name: Alimta
Active Comparator: Arm B

MK-3475 200 mg/m2 IV every 21-days for up to 4 cycles

Patients with CR, PR, or SD by irRC will then be treated with:

For Squamous Carcinoma:

Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles Paclitaxel 200 mg/m2 IV day 1 every 21-days for up to 4 cycles

OR

For Non-squamous Carcinoma

Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles

Drug: MK-3475
Dose frequency of Q3W, Day 1 of each cycle
Other Name: Pembrolizumab
Drug: Carboplatin
Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Other Names:
  • Paraplat
  • Paraplatin
Drug: Paclitaxel
Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Other Name: Taxol
Drug: Pemetrexed
Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Other Name: Alimta



Primary Outcome Measures :
  1. Overall Response Rate (ORR) per RECIST 1.1 [ Time Frame: 18 Months ]
    The primary objective of this randomized phase II trial to determine the overall response rate (ORR per RECIST 1.1) in Chemotherapy naive patients with stage IV NSCLC after the administration of standard platinum-based chemotherapy before MK-3475 (arm A) and administration of MK-3475 administered before standard platinum-based chemotherapy (arm B).


Secondary Outcome Measures :
  1. Compare Progression-Free Survival (PFS) per RECIST 1.1 [ Time Frame: 24 Months ]
    To compare the progression-free survival (PFS) per RECIST 1.1 in previously untreated patients with advanced NSCLC treated with first line carboplatin-based chemotherapy followed by MK-3475 to patients treated with MK-3475 prior to first-line carboplatin-based chemotherapy.

  2. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: 24 Months ]
    To characterize the adverse events related to MK-3475 by frequency, type and grade in patients with Chemotherapy naive advanced NSCLC based on the sequence of administration with first-line chemotherapy.


Other Outcome Measures:
  1. Evaluate the ORR per irRC [ Time Frame: 24 Months ]
    To evaluate the ORR per irRC of MK-3475 administered prior to or after treatment with first-line carboplatin-based chemotherapy in patients with previously untreated NSCLC.

  2. Evaluate PFS per irRC [ Time Frame: 24 Months ]
    To evaluate the PFS per irRC of previously untreated patients with advanced NSCLC who are treated with MK-3475 administered prior to or after first-line carboplatin-based chemotherapy.

  3. Evaluate Response Duration of MK-3475 [ Time Frame: 24 Months ]
    To evaluate the response duration of MK-3475 based on schedule of administration with standard platinum-based chemotherapy in patients with previously untreated advanced NSCLC.

  4. Evaluate the Overall Survival (OS) [ Time Frame: 24 Months ]
    To evaluate the overall survival (OS) of patients with previously untreated advanced NSCLC who received MK-3475 administered prior to or after treatment with first line carboplatin-based chemotherapy.



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. Be ≥ 18 years of age on day of signing informed consent.
  2. Have a life expectancy of at least 3 months.
  3. Have a histologically or cytologically confirmed diagnosis of stage IV NSCLC.
  4. Have a performance status of 0 or 1 on the ECOG.
  5. Have a measurable disease based on RECIST 1.1.
  6. Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of tumor lesion.
  7. In patients with non-squamous non-small cell lung cancer, investigators must be able to produce source documentation of the EGFR mutation status or ALK translocation status.
  8. Demonstrate adequate organ function.
  9. Female patient of childbearing potential should have a negative urine or serum pregnancy test within 72 hours.
  10. Female parents of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile.
  11. Male patients must agree to use an adequate method of contraception.

Exclusion Criteria:

  1. Has received prior treatment with chemotherapy or biologic therapy for stage IV NSCLC.
  2. Is currently participating in or has participated in a study of an investigational agent or using an investigational device.
  3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy.
  4. Has had a prior mAb within 4 weeks prior to study Day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier.
  5. Has had prior chemotherapy or radiation.
  6. Has a known additional malignancy that is progressing or requires active treatment.
  7. Has known active CNS metastases and/or carcinomatous meningitis.
  8. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
  9. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  10. Has an active infection requiring systemic therapy.
  11. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial.
  12. Has known psychiatric or substance abuse disorders.
  13. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial.
  14. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody.
  15. Has a known history of HIV.
  16. Has known active Hepatitis B or Hepatitis C.
  17. Has received a live vaccine within 30 days prior to the planned first dose of study therapy.
  18. Has a known history of active TB.
  19. Hypersensitivity to pembrolizumab or any of it's excipients.

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): NCT02591615


Contacts
Contact: Ed Habermehl info@alliancefoundationtrials.org

Locations
United States, New Hampshire
NH Oncology Recruiting
Hooksett, New Hampshire, United States, 03106
Contact: Douglas Weckstein, MD         
Sponsors and Collaborators
Alliance Foundation Trials, LLC.
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Monica Bertagnolli, MD Alliance Foundation Trials, LLC.

Publications:
Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. doi: 10.1016/S1470-2045(11)70393-X. Epub 2012 Jan 26.
Yang, J.C., et al., Overall Survival in Patients with Advanced Non-small Cell Lung Cancer Harboring Common (Del 19/L858R) Epidermal Growth Factor Receptor Mutations: Pooled Analysis of Two Large Open-label Phase III Studies Comparing Afatinib with Chemotherapy. J Clin Oncol, 2014. 32:5s((suppl; abstr 8004))
Spigel, D., et al., Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastic non-small cell lung cancer. J Clin Oncol, 2013. 31(Suppl; abstr 8008).
Garon, E., et al., Abstract A20: MK-3475 monotherapy for previously treated non-small cell lung cancer: Preliminary safety and clinical activity. . Clin Cancer Res, 2014. 20: p. A20.
Garon, E., et al., Safety and Clinical Activity of MK-3475 in Previously Treated Patients with Non-small Cell Lung CAncer. J Clin Oncol, 2014. 32:5S((suppl;abstr 8020)).
Rizvi, N., et al., Safety and Clinical Activity of MK-3475 as Initial Therapy in Patients with Advanced Non-small Cell Lung Cancer. J Clin Oncol, 2014. 32:5s((suppl; abstr 8007)).
Gettinger, S.N., et al., First-line Nivolumab Monotherapy in Advanced NSCLC: Safety, Efficacy, and Correlation with PD-L1 Status. . J Clin Oncol, 2014. 325s((suppl; abstr 8024)).
Brahmer, J., et al., Survival and long-term follow up of phase I trial of nivolumab (Anti-PD-1; BMS-936558, ONO-4538) in patients with previously treated advanced non-small cell lung cancer. J Clin Oncol, 2013. 31(suppl; abstr 8030).
Antonia, S.J., et al., Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with platinum-based doublet chemotherapy in advanced non-small cell lung cancer. J Clin Oncol, 2014. 32:5s((suppl; abstr 8113)).
Fleiss, J., L. B, and M. Paik, Statistical Methods for Rates and Proportions, J.W. Sons, Editor. 2003: New York.

Responsible Party: Alliance Foundation Trials, LLC.
ClinicalTrials.gov Identifier: NCT02591615     History of Changes
Other Study ID Numbers: AFT-09
First Posted: October 29, 2015    Key Record Dates
Last Update Posted: May 19, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Pembrolizumab
Albumin-Bound Paclitaxel
Carboplatin
Pemetrexed
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors