Study of Pembrolizumab and Chemotherapy With or Without Radiation in Small Cell Lung Cancer (SCLC)

NCT02934503 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 16-01031
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is to assess the efficacy of pembrolizumab added to concurrent chemotherapy with or without radiation therapy in patients with small cell lung cancer (SCLC).

Conditions

Small Cell Lung Cancer (SCLC)

Keywords

Chemotherapy; PD-L1; Thoracic radiotherapy; PD-1; MK-3475

Outcome Measures

Primary Outcomes (1)

• Change in PD-L1 Expression Status as Determined by Immunohistochemistry in Pretreatment and Archival Samples

  up to 5 months

Secondary Outcomes (4)

• Number of Participants With Progression-free Survival (PFS)

  up to 6 months

• Number of Participants With Overall Survival

  up to 9 months

• Response Evaluation Using Response Evaluation Criteria In Solid Tumors (RECIST)

  at 6 weeks

• Response Evaluation Using Response Evaluation Criteria In Solid Tumors (RECIST)

  at 12 weeks

Study Arms (1)

Cisplatin or carboplatin, Etoposide, Pembrolizumab & Radiation

EXPERIMENTAL

Cohort A: cisplatin (75 mg/m\^2) + carboplatin (AUC 6) + etoposide (100mg/m\^2) for four to six, 3-week cycles + pembrolizumab (200 mg) followed by radiation. Pembrolizumab will be started with first cycle of chemotherapy and continued for up to 2 years. Cohort B: Pembrolizumab (200 mg) will be added to standard therapy with cisplatin (75 mg/m2) or carboplatin (AUC 6) and etoposide (100 mg/m2) (and radiation, if appropriate), after one 3- week cycle of standard therapy and continued for up to 2 years. Cohort C: 200 mg IV infusion of Pembrolizumab every 3 weeks over about 30 minutes after completion of standard chemotherapy with cisplatin (75 mg/ m2) and etoposide (100 mg/m2). Treatment with pembrolizumab will continue for up to 2 years. Cohort D: Pembrolizumab 200 mg IV infusion every 3 weeks in vein after completion of standard chemotherapy and radiation. Pembrolizumab will start within 6 weeks of completing radiation therapy and continue for up to 2 years.

Biological: Pembrolizumab; Drug: Cisplatin; Drug: Carboplatin; Drug: Etoposide; Radiation: Radiation therapy

Interventions

Pembrolizumab BIOLOGICAL

200 mg IV fixed dose every 3 weeks until progression or for up to 2 years of therapy.

Also known as: Keytruda

Cisplatin or carboplatin, Etoposide, Pembrolizumab & Radiation

Cisplatin DRUG

75 mg/m2

Also known as: Platinol

Cisplatin or carboplatin, Etoposide, Pembrolizumab & Radiation

Carboplatin DRUG

AUC 6

Also known as: Paraplatin

Cisplatin or carboplatin, Etoposide, Pembrolizumab & Radiation

Etoposide DRUG

IV every 3 weeks for up to 6 cycles (minimum of 4 cycles, maximum of 6).

Also known as: Etopophos

Cisplatin or carboplatin, Etoposide, Pembrolizumab & Radiation

Radiation therapy RADIATION

Thoracic radiotherapy will be given per institutional standards(dose and duration may vary for individual participants).

Cisplatin or carboplatin, Etoposide, Pembrolizumab & Radiation

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically confirmed small cell lung carcinoma not amenable to initial concurrent radiotherapy (extensive-stage disease).
• Participants may have evaluable or measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam.
• Participants in cohort B must have completed 1 cycle of systemic chemotherapy. Therapy with the combination must start no sooner than 3 weeks from the last dose of chemotherapy and no later than 5 weeks from the last dose of chemotherapy. Participants in cohort B must not have had progression of disease prior to the start of therapy.
• Participants in cohort C must have completed systemic therapy (4-6 cycles cisplatin or carboplatin + etoposides) and NOT be a candidate for consolidation thoracic radiotherapy or PCI. Participants in cohort C must initiate therapy with pembrolizumab within 6 weeks of the last dose of chemotherapy (therapy must not start within 2 weeks from the last dose). Participants in cohort C must not have had progression of disease prior to the start of therapy.
• Participants in cohort D must have completed systemic therapy AND have completed either consolidation thoracic radiotherapy or PCI or both completed either consolidation thoracic radiotherapy or PCI or both. Participants in cohort D must initiate therapy with pembrolizumab within 6 weeks of the last dose of radiation. Therapy must not start within 2 weeks from the last dose. Consolidation radiotherapy dose must NOT be more than 3000 centigray (cGy). Participants in cohort D must not have had progression of disease prior to the start of therapy.
• Age \> 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%)
• Life expectancy of greater than 3 months
• Participants must have normal organ and marrow function during screening and on Cycle 1, day 1 as defined below.
• \* Adequate Organ Function Laboratory Values
• System Laboratory Value Hematological
• Absolute neutrophil count (ANC) ≥1,500 /microliter (mcL)
• Platelets ≥100,000 / mcL
• Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Renal

You may not qualify if:

• Participants in cohort A may not have had prior therapy for their disease. Participants in cohort B may not have had more than 1 cycle of systemic therapy (cisplatin or carboplatin + etoposide). Participants in cohort C and D should not have had more than one prior regimen of chemotherapy.
• Participants who have had a CR after pre-study therapy are not eligible for study.
• No thoracic radiation \> 3000 cGy allowed.
• No stroke, myocardial infarction, or major surgery within 3 months of starting on therapy
• Participants who are receiving any other investigational agents or have received investigational therapy or any anti-cancer monoclonal antibody (mAB) within 4 weeks prior to the 1st dose of pembrolizumab.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of non-infectious pneumonitis which required steroids, or any evidence of current, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active Bacillus Tuberculosis (TB)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab, cisplatin, carboplatin, or etoposide.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

Sponsors & Collaborators

• NYU Langone Health: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

pembrolizumab; Cisplatin; Carboplatin; Etoposide; etoposide phosphate; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Therapeutics

Results Point of Contact

• Title: Dr. Joshua Sabari
• Organization: NYU Langone

Joshua.Sabari@nyulangone.org

212-731-6363

Study Officials

• Joshua Sabari, MD,

  NYU Perlmutter Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2016
• First Posted: October 17, 2016
• Study Start: January 23, 2017
• Primary Completion: October 1, 2019
• Study Completion: October 1, 2019
• Last Updated: November 16, 2021
• Results First Posted: November 16, 2021

Record last verified: 2021-10

Locations

US (1)