Small Cell Lung Cancer (SCLC)Phase 2REACTIONNCT02580994
Pembrolizumab in Untreated Extensive SCLC
A Phase 2 study testing Pembrolizumab and cis/carboplatin and etoposide in people with Small Cell Lung Cancer (SCLC), run by European Organisation for Research and Treatment of Cancer - EORTC at 18 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Cancer (SCLC)
- What is being tested?
- Pembrolizumab and cis/carboplatin and etoposide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 125 participants
- Where
- 18 sitesin 3 countries
- Study dates
- 8 Dec 2017to 22 Jun 2022
- 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
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
18 sites in 3 countries.
18 sites in 3 countries
France10 sites
Centre Hospitalier d'Avignon - Hopital Duffaut
Avignon, 84902
CHU de Brest
Brest, 29200
Centre Regional Francois Baclesse
Caen, 14076
Centre Hopitalier Intercommunal De Creteil
Créteil, 94010
Centre Leon Berard
Lyon, 69008
Assistance Publique - Hopitaux de Marseille - Hopital Nord
Marseille, 13015
Centre Hospitalier D'Annecy
Metz-Tessy, 74370
Assistance Publique - Hopitaux de Paris - Hopital Avicenne
Paris, 93009
Centre Paul Strauss
Strasbourg, 67065
Gustave Roussy
Villejuif, 94805
Italy6 sites
Ospedale Cannizzaro
Catania, 95126
Santa Croce e Carle General Hospital
Cuneo, 12100
Azienda Ospedaliero-Universitaria Careggi
Florence, 50134
Istituto Europeo di Oncologia
Milan, 20141
Ospedale San Paolo
Milan, 20142
Ospedale S. Luigi Gonzaga - Universita Di Torino
Orbassano, 10043
United Kingdom2 sites
The Christie NHS Foundation Trust
Manchester, M20 4BX
Sheffield Teaching Hospitals NHS Foundation Trust - Weston Park Hospital
Sheffield, S10 2SJ
About this study
Official title: REACTION: A Phase II Study of Etoposide and Cis/Carboplatin With or Without Pembrolizumab in Untreated Extensive Small Cell Lung Cancer
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.
Read the 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.
- Conditions
- Small Cell Lung Cancer (SCLC)
- Being tested
- Pembrolizumab, cis/carboplatin and etoposide
- Keywords
- Extended Disease Small Cell Lung Cancer, phase II, randomized, pembrolizumab, cross-over, etoposide, cisplatin, carboplatin, rechallenge
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called MK-3475, Keytruda
IV infusion at the dose of 200 mg on day 1 every 3 weeks
cis/carboplatin and etoposideDrug
Also called Platinol, Paraplatin and Etopophos
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
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab + chemotherapy | Experimental | 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 Receives: Drug: Pembrolizumab; Drug: cis/carboplatin and etoposide |
| Chemotherapy | Active comparator | 4 cycles of cis/carboplatin and etoposide Receives: Drug: cis/carboplatin and etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Increase in Progression Free Survival
Measured: 6 months
Secondary outcomes (1)
Overall Survival
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2015 (estimated)
- Study start8 Dec 2017
- Primary completion22 Sep 2020
- Study completion22 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Small Cell Lung Cancer (SCLC)Studies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- 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
- Crossover
- Masking
- None (open label)
- Enrolment
- 125 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02580994
- Sponsor's protocol ID
- EORTC-1417-LCG
- Other IDs
- 2014-003090-42, 2014
- Acronym
- REACTION
- Status last verified
- Dec 2023
- First submitted
- 19 Oct 2015
- Last updated
- 11 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- REACTION: A Phase II Study of Etoposide and Cis/Carboplatin With or Without Pembrolizumab in Untreated Extensive Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT02580994
- Acronym / sponsor ID
- REACTION / EORTC-1417-LCG
- Conditions
- Small Cell Lung Cancer (SCLC)
- Keywords
- Extended Disease Small Cell Lung Cancer, phase II, randomized, pembrolizumab, cross-over, etoposide, cisplatin, carboplatin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 125 participants (actual)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 8 Dec 2017 (actual)
- Primary completion
- 22 Sep 2020 (actual)
- Study completion
- 22 Jun 2022 (actual)
- First posted
- 20 Oct 2015 (estimated)
- 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.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab + chemotherapy | Experimental | Drug: Pembrolizumab, Drug: cis/carboplatin and etoposidePembrolizumab, 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 |
| Chemotherapy | Active comparator | Drug: cis/carboplatin and etoposide4 cycles of cis/carboplatin and etoposide |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (18 listed)
- 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
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 |
|---|---|---|
| PembrolizumabAlso: MK-3475, KeytrudaIV infusion at the dose of 200 mg on day 1 every 3 weeks | Drug | Pembrolizumab + chemotherapy |
| cis/carboplatin and etoposideAlso: Platinol, Paraplatin and EtopophosCisplatin 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 | Drug | Chemotherapy, Pembrolizumab + chemotherapy |
Primary outcome
Increase in Progression Free Survival
Time frame: 6 months
1 secondary outcome
Overall Survival
Time frame: 12 months
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 11 Dec 2023.
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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.
The record lists no contact. Use the official record to reach the sponsor.
18 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab and cis/carboplatin and etoposide in people with Small Cell Lung Cancer (SCLC), run by European Organisation for Research and Treatment of Cancer - EORTC at 18 sites in 3 countries.
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 16 inclusion and 18 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 11 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in France, Italy, United Kingdom. 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?
Increase in Progression Free Survival (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Dec 2023.