Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pembrolizumab in Untreated Extensive SCLC (REACTION)

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.
 
ClinicalTrials.gov Identifier: NCT02580994
Recruitment Status : Active, not recruiting
First Posted : October 20, 2015
Last Update Posted : November 19, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme (MSD)
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

Brief Summary:
This is a multicenter, open-label, two armed, controlled, and randomized phase II trial investigating the activity of pembrolizumab in combination with standard chemotherapy in Extensive Disease (ED)-SCLC.

Condition or disease Intervention/treatment Phase
Small Cell Lung Cancer (SCLC) Drug: Pembrolizumab Drug: cis/carboplatin and etoposide Phase 2

Detailed Description:

This is a multicenter, open-label, two armed, controlled, and randomized phase II trial investigating the activity of pembrolizumab in combination with standard chemotherapy in ED-SCLC.

Extended stage Small Cell Lung Cancer (SCLC) patients will be registered, after signing the informed consent, and then centrally randomized 1:1 to the experimental arm (Arm A) and the control arm (Arm B).

Cross-over at the time of disease progression will be allowed for arm B only.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 125 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: REACTION: A Phase II Study of Etoposide and Cis/Carboplatin With or Without Pembrolizumab in Untreated Extensive Small Cell Lung Cancer
Actual Study Start Date : December 8, 2017
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020


Arm Intervention/treatment
Experimental: Pembrolizumab + chemotherapy
Pembrolizumab, in combination with cis/carboplatin and etoposide for 4 cycles intravenous 200mg on day 1 (every 3 weeks), pembrolizumab continued alone as continuation maintenance until progressive disease
Drug: Pembrolizumab
IV infusion at the dose of 200 mg on day 1 every 3 weeks
Other Names:
  • MK-3475
  • Keytruda

Drug: cis/carboplatin and etoposide
Cisplatin 80 mg/m2 or Carboplatin Area Under the Curve (AUC) 5 IV infusion on day 1 Etoposide 100 mg/m2 IV infusion on day 1, 2 and 3
Other Name: Platinol, Paraplatin and Etopophos

Active Comparator: Chemotherapy
4 cycles of cis/carboplatin and etoposide
Drug: cis/carboplatin and etoposide
Cisplatin 80 mg/m2 or Carboplatin Area Under the Curve (AUC) 5 IV infusion on day 1 Etoposide 100 mg/m2 IV infusion on day 1, 2 and 3
Other Name: Platinol, Paraplatin and Etopophos




Primary Outcome Measures :
  1. Increase in Progression Free Survival [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 12 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed SCLC
  • Extended disease according to the criteria of the Veteran's Administration - Lung Cancer Group (VALG): disease extended beyond a hemithorax and the supraclavicular node area. Pleural involvement will be considered as extended disease
  • Assessment of adequate tissue availability for Program Cell Death-Ligand 1 (PD-L1) immunohistochemistry testing
  • Before patient registration, written informed consent must be given according to International Conference of Harmonization-Good Clinical Practice (ICH-GCP), and national/local regulations
  • Tumor assessment performed within 10 days before randomization. Patient may or may not have measurable disease
  • Previous palliative brain radiotherapy is allowed if terminated at least 3 weeks before randomization
  • Partial or complete response according to RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 after 2 cycles of any platinum-based induction chemotherapy regimen
  • Adequate hematopoietic, hepatic and renal function within 10 days before randomization defined as follows:

    • Absolute neutrophil count (ANC) ≥ 1.5 x 10E9/L, Hemoglobin (Hb) ≥ 9 g/dL and platelet count ≥ 100 x 10E9/L
    • Serum creatinine clearance ≥ 60 mL/min as calculated with Cockcroft-Gault formula
    • Bilirubin ≤ 1.5 x Upper Limit Normal (ULN), Alanine Aminotransferase (ALT) (SGTP) and Aspartate Transaminase (AST) (SGOT) ≤ 3 x ULN
    • International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
    • Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as a PTT is within therapeutic range of intended use of anticoagulants N.B. Lactate Dehydrogenase (LDH) level assessment is mandatory for randomization
  • Women of child bearing potential (WOCBP) must have a negative urine or serum pregnancy test within 72 hours before randomization
  • Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by investigator, during the study treatment period and for at least 120 days after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.
  • Female subjects who are breast feeding should discontinue nursing before randomization and until 120 days after the last study treatment

Exclusion Criteria:

  • Prior systemic therapy for SCLC; previous treatment with platinum and etoposide concomitant with radiotherapy (RT) for limited disease is allowed if terminated at least 1 year before patient randomization
  • known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (i.e. without evidence of progression by imaging and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and have not received steroids for at least 7 days before randomization
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 3-4 (at registration) (patients who are judged by the investigator to be PS 2 due to primary disease are the only PS 2 patients who are eligible)
  • ECOG PS 2-4 (at randomization)
  • Less than 3 month life expectancy
  • History of interstitial lung disease (ILD) or a history of (non-infectious) pneumonitis that required oral or IV steroids (other than Chronic Obstructive Pulmonary Disease [COPD] exacerbation) or current pneumonitis or current evidence of ILD
  • Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs), any replacement therapy (i.e. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed
  • Previous allogeneic tissue/solid organ transplant
  • Active infection requiring therapy
  • Known history of Human Immunodeficiency Virus (HIV) (known HIV 1/2 antibodies positive). No known active Hepatitis B or C. Active Hepatitis B is defined as a known positive HBsAg results. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative Hepatitis C Virus (HCV) RNA results greater than the lower limits of detection of the assay
  • Ongoing grade ≥ 2 peripheral neuropathy
  • Prior treatment with platinum, anti-PD-1, anti-PD-L1/2, anti interleukin-7 receptor-alpha (anti-CD127), Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) modulators
  • Chronic use of immunosuppressive agents and/or systemic corticosteroids or any use in the 3 days before randomization:
  • Corticosteroid use on study for management of pembrolizumab Events of Clinical Interest (ECIs), as pre-medication for the administration of chemotherapies, and/or a pre-medication for contrast allergies/reactions is allowed
  • Daily prednisone at doses of 5-7.5 mg is allowed as an example of replacement therapy. Equivalent hydrocortisone doses are also permitted if administered as a replacement therapy
  • Prior use of live vaccines within 30 days before randomization. Examples of live vaccines include, but are not limited to, the following : measles, mumps, rubella, chicken pox, shingles, yellow fever, influenza A virus subtype (H1N1) flu, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine
  • Presence of any clinical, psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
  • Concurrent treatment with any investigational agent within 4 weeks before randomization

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): NCT02580994


Locations
Show Show 26 study locations
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Merck Sharp & Dohme (MSD)
Investigators
Layout table for investigator information
Principal Investigator: Benjamin Besse, MD, PhD Institut Gustave Roussy, Villejuif, France
Principal Investigator: Jessica Menis, MD Istituto Oncologico Veneto IRCCS, Padova, Italy
Layout table for additonal information
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT02580994    
Other Study ID Numbers: EORTC-1417-LCG
2014-003090-42 ( EudraCT Number )
First Posted: October 20, 2015    Key Record Dates
Last Update Posted: November 19, 2019
Last Verified: November 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
Extended Disease Small Cell Lung Cancer
phase II
randomized
pembrolizumab
cross-over
etoposide
cisplatin
carboplatin
rechallenge
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carboplatin
Etoposide
Pembrolizumab
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological