Clinical Trials /

Pembrolizumab and Concurrent Chemoradiotherapy or Radiation Therapy in Treating Patients With Small Cell Lung Cancer

NCT02402920

Description:

This phase I trial studies the side effects and best dose of pembrolizumab when given together with chemoradiotherapy or radiation therapy in treating patients with small cell lung cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving chemotherapy with radiation therapy may kill more cancer cells. Giving pembrolizumab with chemoradiotherapy or radiation therapy may be a better treatment for small cell lung cancer.

Related Conditions:
  • Neuroendocrine Tumor
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab and Concurrent Chemoradiotherapy or Radiation Therapy in Treating Patients With Small Cell Lung Cancer
  • Official Title: Phase I Trial of MK-3475 and Concurrent Chemo/Radiation for the Elimination of Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2014-1003
  • SECONDARY ID: NCI-2015-00598
  • SECONDARY ID: 2014-1003
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT02402920

Conditions

  • Extensive Stage Small Cell Lung Carcinoma
  • Limited Stage Small Cell Lung Carcinoma
  • Neuroendocrine Neoplasm

Interventions

DrugSynonymsArms
CarboplatinBlastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, RibocarboPart A (LS-SCLC, pembrolizumab, chemoradiotherapy)
CisplatinAbiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, PlatosinPart A (LS-SCLC, pembrolizumab, chemoradiotherapy)
EtoposideDemethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213Part A (LS-SCLC, pembrolizumab, chemoradiotherapy)
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Part A (LS-SCLC, pembrolizumab, chemoradiotherapy)

Purpose

This phase I trial studies the side effects and best dose of pembrolizumab when given together with chemoradiotherapy or radiation therapy in treating patients with small cell lung cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving chemotherapy with radiation therapy may kill more cancer cells. Giving pembrolizumab with chemoradiotherapy or radiation therapy may be a better treatment for small cell lung cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Safety of pembrolizumab (MK 3475) plus chemotherapy (chemo)/radiation for limited-stage
      small-cell lung cancer (LS-SCLC).

      II. Safety of MK-3475 plus radiation for extensive-stage small-cell lung cancer (ES-SCLC).

      SECONDARY OBJECTIVES:

      I. MK-3475 will improve progression free survival (PFS) compared to historical controls for
      LS-SCLC and ES-SCLC.

      OUTLINE: This is a dose-escalation study of pembrolizumab. Patients are assigned to either
      Part A or Part B based on diagnosis.

      PART A (LS-SCLC): Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1
      and undergo radiation therapy twice daily (BID) 5 days a week for 3 weeks. Patients also
      receive cisplatin IV over 2 hours or carboplatin IV over 30 minutes and etoposide IV over 4
      hours on days 1, 2, and 3. Treatment repeats every 3 weeks for 16 courses (1 course for
      radiation therapy, 4 courses for chemotherapy) in the absence of disease progression or
      unacceptable toxicity. Patients who achieve systemic disease control and do not exhibit
      severe (grade > 3) pembrolizumab related toxicity during/after completion of 16 courses may
      receive 16 additional courses of pembrolizumab in the absence of disease progression or
      unacceptable toxicity.

      PART B (ES-SCLC): Beginning after the completion of chemotherapy, patients receive
      pembrolizumab IV over 30 minutes on day 1 and undergo radiation therapy BID 5 days a week for
      3 weeks. Treatment repeats every 3 weeks for 16 courses (1 course for radiation therapy) in
      the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, all patients are followed up at 30 days and then every
      12 weeks.
    

Trial Arms

NameTypeDescriptionInterventions
Part A (LS-SCLC, pembrolizumab, chemoradiotherapy)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1 and undergo radiation therapy BID 5 days a week for 3 weeks. Patients also receive cisplatin IV over 2 hours or carboplatin IV over 30 minutes and etoposide IV over 4 hours on days 1, 2, and 3. Treatment repeats every 3 weeks for 16 courses (1 course for radiation therapy, 4 courses for chemotherapy) in the absence of disease progression or unacceptable toxicity. Patients who achieve systemic disease control and do not exhibit severe (grade > 3) pembrolizumab related toxicity during/after completion of 16 courses may receive 16 additional courses of pembrolizumab in the absence of disease progression or unacceptable toxicity.
  • Carboplatin
  • Cisplatin
  • Etoposide
  • Pembrolizumab
Part B (ES-SCLC, pembrolizumab, radiation therapy)ExperimentalBeginning after the completion of chemotherapy, patients receive pembrolizumab IV over 30 minutes on day 1 and undergo radiation therapy BID 5 days a week for 3 weeks. Treatment repeats every 3 weeks for 16 courses (1 course for radiation therapy) in the absence of disease progression or unacceptable toxicity.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Be willing and able to provide written informed consent/assent for the trial

          -  Have a performance status of 0 or 1 or 2 on the Eastern Cooperative Oncology Group
             (ECOG) performance scale

          -  Absolute neutrophil count (ANC) >= 1,500/mcL (performed within 10 days of treatment
             initiation)

          -  Platelets >= 100,000/mcL (performed within 10 days of treatment initiation)

          -  Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (performed within 10 days of treatment
             initiation)

          -  Serum creatinine or measured or calculated creatinine clearance (glomerular filtration
             rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) =<
             1.5 X upper limit of normal (ULN) or >= 60 mL/min for subject with creatinine levels >
             1.5 X institutional ULN (creatinine clearance should be calculated per institutional
             standard) (performed within 10 days of treatment initiation)

          -  Serum total bilirubin =< 1.5 X ULN or direct bilirubin =< ULN for subjects with total
             bilirubin levels > 1.5 ULN (performed within 10 days of treatment initiation)

          -  Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and
             alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 2.5 X
             ULN or =< 5 X ULN for subjects with metastatic malignant neoplasm in the liver (liver
             metastases) (performed within 10 days of treatment initiation)

          -  International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless
             subject is receiving anticoagulant therapy as long as PT or partial thromboplastin
             time (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 PT or PTT is within therapeutic range of intended use
             of anticoagulants (performed within 10 days of treatment initiation)

          -  Female subjects of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication; if
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required

          -  Female subjects of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study through 120 days after the last dose of study medication; subjects of
             childbearing potential are those who have not been surgically sterilized or have not
             been free from menses for > 1 year

          -  Male subjects should agree to use an adequate method of contraception starting with
             the first dose of study therapy through 120 days after the last dose of study therapy

          -  Histologic diagnosis of either limited stage SCLC (LS-SCLC), or extensive stage SCLC
             (ES-SCLC) or neuroendocrine tumor

        Exclusion Criteria:

          -  Is currently participating in or has participated in a study of an investigational
             agent (except glutamine) or using an investigational device within 2 weeks of the
             first dose of treatment

          -  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; with the exception of physiologic steroid replacement

          -  Has had a prior monoclonal antibody within 2 weeks prior to study day 1 or who has not
             recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents
             administered more than 4 weeks earlier

          -  Has had prior chemotherapy, targeted small molecule therapy, within 2 weeks prior to
             study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse
             events due to a previously administered agent; prior radiation does not require a
             washout period; note: subjects with =< grade 2 neuropathy are an exception to this
             criterion and may qualify for the study; note: if subject received major surgery, they
             must have recovered adequately from the toxicity and/or complications from the
             intervention prior to starting therapy

          -  Has a known additional malignancy that is progressing or requires active treatment;
             exceptions include skin basal cell carcinoma (basal cell carcinoma of the skin), skin
             squamous cell carcinoma (squamous cell carcinoma of the skin), or in situ cervical
             cancer that has undergone potentially curative therapy

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis; subjects with previously treated brain metastases may participate provided
             they are stable (without evidence of progression by imaging for at least four weeks
             prior to the first dose of trial treatment and any neurologic symptoms have returned
             to baseline), have no evidence of new or enlarging brain metastases, and are not using
             steroids for at least 7 days prior to trial treatment

          -  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; subjects with vitiligo or
             resolved childhood asthma/atopy would be an exception to this rule; subjects that
             require intermittent use of bronchodilators or local steroid injections would not be
             excluded from the study; subjects with hypothyroidism stable on hormone replacement or
             Sjogren's syndrome will not be excluded from the study

          -  Has evidence of interstitial lung disease or active, non-infectious pneumonitis

          -  Has an active infection requiring systemic therapy

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator

          -  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

          -  Has received prior therapy with an anti-programmed cell death-1 (PD-1),
             anti-programmed cell death-ligand 1 (PD-L1), anti-programmed cell death 1 ligand 2
             (PD-L2), anti-cluster of differentiation (CD)137

          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

          -  Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
             hepatitis C (e.g., hepatitis C virus ribonucleic acid [HCV RNA] [qualitative] is
             detected)

          -  Has received a live vaccine within 30 days prior to the first dose of trial treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose of pembrolizumab with concurrent chemoradiation determined by dose limiting toxicities graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Part A)
Time Frame:Up to 22 days after therapy initiation
Safety Issue:
Description:Frequency of adverse events will be tabulated by grade, type, and dose/cohort. Relative frequencies and confidence intervals will also be constructed.

Secondary Outcome Measures

Measure:Response rate
Time Frame:Up to 8 years
Safety Issue:
Description:Will be performed using Global Immune Related Response Criteria that factors all indexed and non-indexed lesions, In-Field Immune Related Response Criteria in which only non-radiation therapy-treated lesions and non-index lesions arising outside the radiation therapy planning target volume will be considered, and Out-Field Immune Related Response Criteria in which only non-radiation therapy-treated lesions and non-index lesions arising outside the radiation therapy planning target volume will be considered.
Measure:Progression free survival
Time Frame:Up to 8 years
Safety Issue:
Description:Time to event distributions for progression free survival will be estimated via Kaplan-Meier analysis.
Measure:Overall survival
Time Frame:Up to 8 years
Safety Issue:
Description:Time to event distributions for overall response will be estimated via Kaplan-Meier analysis.
Measure:Biomarker response
Time Frame:Up to 8 years
Safety Issue:
Description:Descriptive analysis will include a global assessment of patient outcomes for parts A and B separately.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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