Clinical Trials /

Pembro and Vorinostat for Patients With Stage IV Non-small Cell Lung Cancer (NSCLC)

NCT02638090

Description:

The main purpose of this study is to see whether the combination of two drugs called pembrolizumab and vorinostat can help people with advanced lung cancer. Researchers also want to find out if the combination of pembrolizumab and vorinostat is safe and tolerable. This study will compare the effects of the combination of two drugs called pembrolizumab and vorinostat with the effects of pembrolizumab alone. The U.S. Food and Drug Administration (FDA) has approved pembrolizumab for use to treat a deadly skin cancer called melanoma and lung cancer and vorinostat to treat some forms of blood and lymph node cancers.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembro and Vorinostat for Patients With Stage IV Non-small Cell Lung Cancer (NSCLC)
  • Official Title: A Phase I/II Study of Pembrolizumab and Vorinostat in Patients With Immune Therapy Naïve and Immune Therapy Pretreated Stage IV NSCLC

Clinical Trial IDs

  • ORG STUDY ID: MCC-18494
  • NCT ID: NCT02638090

Conditions

  • Lung Cancer
  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
VorinostatZolinzaPhase I Dose Escalation
PembrolizumabKEYTRUDAPhase I Dose Escalation

Purpose

The main purpose of this study is to see whether the combination of two drugs called pembrolizumab and vorinostat can help people with advanced lung cancer. Researchers also want to find out if the combination of pembrolizumab and vorinostat is safe and tolerable. This study will compare the effects of the combination of two drugs called pembrolizumab and vorinostat with the effects of pembrolizumab alone. The U.S. Food and Drug Administration (FDA) has approved pembrolizumab for use to treat a deadly skin cancer called melanoma and lung cancer and vorinostat to treat some forms of blood and lymph node cancers.

Detailed Description

      A Phase I/Randomized Phase II clinical trial of pembrolizumab and vorinostat in Eastern
      Cooperative Oncology Group (ECOG) 0-1 patients with immune therapy naïve and immune therapy
      pretreated locally advanced or metastatic NSCLC who have progressed through one prior line
      of therapy.

      The begins with a phase I dose escalation utilizing the modified continuous reassessment
      method (O'Quigley, Pepe, & Fisher, 1990). This would be followed by a phase I expansion at
      the maximum tolerated dose (MTD) in 18 NSCLC patients who have been previously treated with
      anti-PD-1 or anti-PD-L1 therapy. In parallel, a separate phase II arm will randomize 70
      patients to a pembrolizumab alone group and a pembrolizumab plus vorinostat group.
    

Trial Arms

NameTypeDescriptionInterventions
Phase I Dose EscalationExperimentalLevel 1: Vorinostat 200mg by mouth (PO) Daily; Pembrolizumab 200 mg intravenously (IV) every (Q) 3 weeks. Level 2: Vorinostat 400 mg PO Daily; Pembrolizumab 200 mg IV Q3 weeks
  • Vorinostat
  • Pembrolizumab
Phase Ib ExpansionExperimentalPembrolizumab plus Vorinostat. Level 1: Maximum Tolerated Dose (MTD)
  • Vorinostat
  • Pembrolizumab
Arm A: PembrolizumabActive ComparatorPembrolizumab treatment only. Level 1: Pembrolizumab 200 mg Q3 wks
  • Pembrolizumab
Arm B: Pembrolizumab plus VorinostatActive ComparatorPembrolizumab plus Vorinostat treatment. Level 1: MTD
  • Vorinostat
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Willing and able to provide written informed consent/assent for the trial.

          -  Be ≥ 18 years of age on day of signing informed consent.

          -  Have measurable disease based on Response Evaluation Criteria in Solid Tumors
             (RECIST) 1.1.

          -  Have archival tissue where available. Those participants enrolled on the phase 1
             escalation trial where archival tissue is not available will undergo a fresh biopsy
             where clinically feasible after discussion with the sponsor.

          -  In addition, participants enrolled on the phase 1 dose escalation, phase 1 expansion
             or Phase II trial must be willing and able to provide tissue from a newly obtained
             core or excisional biopsy of a tumor lesion.

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale.

          -  Demonstrate adequate organ function.

          -  Have a histologic or cytologic diagnosis of Stage IV non-small cell lung cancer
             (NSCLC).

          -  Have progression from at least one prior line of therapy, with progression occurring
             no more than 6 months after the end of therapy.

          -  Females of childbearing potential should have a negative urine or serum pregnancy
             within 72 hours prior to receiving the first dose of study medication.

          -  Females 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.

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

        Exclusion Criteria:

          -  Is currently participating in and receiving study therapy or has participated in a
             study of an investigational agent and received study therapy or used an
             investigational device within 4 weeks of the first dose of treatment.

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at doses
             ≥ 10 mg prednisone or any other form of systemic immunosuppressive therapy within 7
             days prior to the first dose of trial treatment. Participants are permitted to use
             topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with
             minimal systemic absorption). Physiologic replacement doses of systemic
             corticosteroids are permitted, even if >= 10 mg/day prednisone equivalents. A brief
             course (≤28 days) of corticosteroids for prophylaxis (e.g., contrast dye allergy) or
             for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity
             reaction caused by contact allergen) is permitted.

          -  Has a known history of tuberculosis (TB) Disease (Mycobacterium tuberculosis).

          -  Hypersensitivity to pembrolizumab, vorinostat or any of its excipients.

          -  Participants enrolled on the phase II randomized trial, who have had prior treatment
             with a PD1 or PDL1 inhibitor, anti-CTLA 4 antibody or any other antibody or drug that
             specifically targets immune checkpoint pathway (i.e. not "immune therapy naïve").
             -Note: For those enrolled in the phase I dose escalation, prior use of a PD1 or PDL1,
             anti-CTLA4 antibody or any other antibody or drug that specifically targets immune
             checkpoint pathway is allowed. For all participants in all phases, prior use of a
             vaccine for treatment of cancer is allowed.

          -  Participants enrolled in the phase Ib expansion who have never previously been
             treated with a PD1 or PDL1 inhibitor, anti-CTLA 4 antibody or any other antibody or
             drug that specifically targets immune checkpoint pathway in the past (i.e. not
             "pre-treated").

          -  Participants who have received thoracic radiation >30Gy within 6 months of the first
             dose of pembrolizumab.

          -  Patients taking any HDACi other than vorinostat.

          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 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 with 3 weeks, or targeted small molecule therapy or
             radiation 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.
             Note: Patients with ≤ Grade 2 neuropathy are an exception to this criterion and may
             qualify for the study. Note: Patients with any grade alopecia are an exception to
             this criterion and may qualify for the study.

          -  If participant 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 basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy, or in situ cervical cancer.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Previously treated brain metastases may be an exception if stable and
             specific other criteria are met.

          -  Has active autoimmune disease that has required systemic treatment in the past 2
             years. Replacement therapy is not considered a form of systemic treatment. Subjects
             are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual
             hypothyroidism due to autoimmune condition only requiring hormone replacement,
             psoriasis not requiring systemic treatment, or conditions not expected to recur in
             the absence of an external trigger.

          -  Has known history of, or any evidence of active, non-infectious pneumonitis.

          -  Has an active infection requiring systemic therapy.

          -  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 a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

          -  Has received a live vaccine within 30 days of planned start of study therapy. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis.

          -  Has evidence of interstitial lung disease
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I: Maximum Tolerated Dose (MTD)
Time Frame:Up to 12 months
Safety Issue:
Description:The maximum tolerated dose (MTD) corresponding to a risk of dose limiting toxicity (DLT) occurring in 30% of patients. DLTs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03). A DLT will be defined as any Grade 3 or higher toxicity that occurs during the DLT evaluation period. Toxicity that is clearly and directly related to the primary disease or to another etiology is excluded from this definition.

Secondary Outcome Measures

Measure:Phase II: Progression Free Survival (PFS) per Treatment Arm
Time Frame:Up to 2 years
Safety Issue:
Description:PFS will be measured from the start of treatment with pembrolizumab and vorinostat until the documentation of disease progression or death due to any cause, whichever occurs first. Progression: One or more of the following must occur: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • advanced lung cancer
  • immune therapy naive
  • immune therapy pre-treated
  • NSCLC
  • Stage IV lung cancer
  • pembrolizumab
  • vorinostat
  • immunogenicity

Last Updated

December 12, 2016