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Pembrolizumab (Immunotherapy Drug) in Combination With Guadecitabine and Mocetinostat (Epigenetic Drugs) for Patients With Advanced Lung Cancer.

This study is currently recruiting participants.
Verified November 2017 by Memorial Sloan Kettering Cancer Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT03220477
First Posted: July 18, 2017
Last Update Posted: November 17, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Merck Sharp & Dohme Corp.
Astex Pharmaceuticals
Mirati Therapeutics Inc.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center
  Purpose
The purpose of this study is to test the safety of a combination of three drugs, pembrolizumab, guadecitabine and mocetinostat. Pembrolizumab is a drug given by vein and all patients will receive the same dose. Guadecitabine and mocetinostat will be given at different doses to find out what effects, if any, they have on treating your cancer and side effects.

Condition Intervention Phase
Lung Cancer Drug: Pembrolizumab Drug: Guadecitabine Drug: Mocetinostat Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Intervention Model Description:
Single-arm, open-label, multi-center, therapeutic study. All patients will be assigned to receive all three study therapies. The phase 1 portion of the study will proceed as a 3+3 dose-escalation with escalating doses of guadecitabine and mocetinostat, along with fixed dose of pembrolizumab.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/Ib Study of Combined Pembrolizumab Plus Guadecitabine and Mocetinostat for Patients With Advanced NSCLC (DOSE SELECTION)

Resource links provided by NLM:


Further study details as provided by Memorial Sloan Kettering Cancer Center:

Primary Outcome Measures:
  • number of patients with adverse events [ Time Frame: 1 year ]
    events occurring on or after treatment on the first day of any study therapy will be summarized by dose cohort, toxicity term, CTCAE v4.0 grade

  • response rate (Phase Ib) [ Time Frame: within 6 months of treatment ]
    Tumor response will be assessed using RECIST 1.1. All responses must be confirmed on subsequent scan to be considered a true response.


Estimated Enrollment: 57
Actual Study Start Date: August 4, 2017
Estimated Study Completion Date: July 2020
Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: pembrolizumab plus guadecitabine and mocetinostat
Pembrolizumab given IV; guadecitabine given SQ, mocetinostat given PO.
Drug: Pembrolizumab
Pembrolizumab will be administered at 200mg IV on day 1 of each 21 day cycle.
Drug: Guadecitabine
Guadecitabine will be administered subcutaneously given daily on days 1-5 of each cycle with escalating doses by cohort.
Drug: Mocetinostat
Mocetinostat will be administered orally with escalating doses on days 8, 10, 13, 15, 17 and 20 of each cycle with escalating doses by cohort.

  Eligibility

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient must be capable, willing, and able to provide written, informed consent
  • Age ≥ 18 years old
  • Histologically-confirmed stage IIIb or IV NSCLC by the enrolling institution

    a. Patients who are highly suspected to have stage IIIb or IV NSCLC and who are planned for a standard-of-care diagnostic biopsy/resection may also be enrolled. Patients who are confirmed to have stage IIIb or IV NSCLC will be eligible to continue with screening procedures. Those who are found after surgery/biopsy to not have stage IIIb or IV NSCLC will not be eligible continue with screening procedures and may not receive study therapy.

  • Previously treated with no more than one line of prior systemic therapy for stage IIIb or IV lung cancer.

    1. For patients who have previously treated one line of prior systemic therapy for stage IIIb or IV lung cancer, they must have exhibited evidence of disease progression clinically and/or radiographically on or after that treatment.
    2. Patients who previously received neoadjuvant, concurrent, or adjuvant chemotherapy for localized NSCLC and then recurred within 6 months of completing chemotherapy will be considered as having received one line of prior therapy. Patients who relapse > 6 months after completing chemotherapy as part of neoadjuvant/concurrent/adjuvant therapy for localized disease, and thereafter receive additional one line of chemotherapy at the time of metastatic disease will be eligible.
    3. Maintenance therapy does not count as a separate line of therapy
  • Measurable by RECIST v1.1 (those undergoing pre-treatment resection must have imaging assessment after resection to determine measurability)

    a. Previously irradiated sites of tumor may be considered measurable if there is radiographic progression at that site subsequent to the time of completing radiation.

  • Have a safely biopsiable tumor lesion and be willing to undergo a pre-treatment and ontreatment core biopsy a. Pretreatment tissue should be collected via core biopsy, ideally of a non-target lesion. b. Patients may not have intervening systemic anti-cancer therapy between the time of pre-treatment biopsy/resection and initiating study treatment.
  • ECOG performance status of 0-1.
  • Adequate hematologic, renal, and/or hepatic function (following criteria must be met within 28 days of C1D1):

    1. ANC ≥ 1,500/mm3 (≥ 1. 5 × 10^9/L)
    2. Hemoglobin ≥ 9.0 g/dL
    3. Platelet count ≥ 100,000/ul (≥ 100,000 per mm3)
    4. Serum creatinine ≤ 1.5 x ULN OR, for subjects with creatinine levels >1.5 x ULN, an estimated creatinine clearance of ≥ 40 mL/min calculated using the Cockcroft and Gault formula ((140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female)
    5. Total bilirubin ≤ 1.5 x ULN OR, for subjected with total bilirubin levels >1.5 x ULN, a direct bilirubin ≤ ULN
    6. AST and ALT ≤ 3 x UNL (unless elevated transaminases are felt to be directly related to metastatic disease involving the liver, in which case AST and ALT must be ≤ 5x ULN)
  • Women of childbearing potential (WOCBP) † must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 28 days of C1D1.

    † A woman of childbearing potential is a sexually mature female who: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e. has had menses at any time in the preceding 24 consecutive months).

  • Effective contraception:

    1. Women of childbearing potential must agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 120 days after the last dose of study therapy, or agree to completely abstain from heterosexual intercourse.
    2. Male subjects, even if surgically sterilized (i.e., status post vasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study therapy, or agree to completely abstain from heterosexual intercourse.
  • Willing to comply with clinical trial instructions and requirements, including mandatory biopsies.

Exclusion Criteria:

  • Presence of targetable EGFR mutations or ALK re-arrangements.

    a. All patients with adenocarcinoma histology must be tested for EGFR and ALK status, unless a KRAS mutation is detected in which case EGFR/ALK testing is not required.

  • History of allergy to study drug components or history of severe hypersensitivity reaction of any monoclonal antibody.
  • History of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
  • Prior treatment with immune checkpoint inhibitor, including (but not limited to) those targeting PD-1, PD-L1, PD-L2, CTLA-4, CD137, GITR, TIM3, LAG3, or OX40.
  • Any systemic anti-cancer therapy within 3 weeks prior to C1D1 of study therapy, with the following exception:

    a. Any prior investigational anti-cancer therapy and/or monoclonal antibody is not permitted within 4 weeks of C1D1.

  • Ongoing adverse event from previously administered systemic anti-cancer therapy unless has recovered to ≤ grade 1 or at baseline prior to C1D1.

    a. Subjects with any grade alopecia or ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.

  • Patients who have not previously been treated with platinum-based based doublet chemotherapy and who, in the judgment of the investigator, have rapidly progressive disease such that serious complications may arise from disease progression within the next 12 weeks will be excluded.
  • Non-CNS radiotherapy within 1 week prior to C1D1 of study therapy
  • Active infection requiring systemic therapy
  • Known history of previous clinical diagnosis of tuberculosis.
  • Prior or current systemic immunosuppressive therapy (> 10 mg/day prednisone equivalents) within 7 days prior to C1D1 of study therapy. Inhaled, ocular, intra-articular, intranasal, and topical corticosteroids are permitted in absence of active autoimmune disease.

    a. Adrenal replacement doses are permitted in the absence of active autoimmune disease.

  • Has diagnosis of immunodeficiency
  • History of allogeneic organ transplant.
  • Patients with known or suspected history of autoimmune disease.

    a. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, resolved childhood asthma/atopy, patients with asthma requiring intermittent bronchodilator therapy, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. i. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

  • Other active malignancy that is progressing, requires concurrent intervention, and/or could be mistaken for the malignancy under study during disease assessments.
  • Patients with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless definitive therapy has been completed at least 1 year prior to study entry and the patient is now without evidence of disease from that malignancy and no additional therapy is required or anticipated to be required during the study period.
  • Known untreated brain or leptomeningeal metastasis.

    a. Patients with brain metastases are eligible if metastases have been adequately treated and neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least two weeks prior to C1D1 and meet requirements related to steroids noted in above Exclusions Criteria 6.2.10.

  • History of stroke or transient ischemic attack within the previous 6 months.
  • Any of the following cardiac abnormalities:

    1. Unstable angina pectoris
    2. Congestive heart failure ≥ NYHA Class 3
    3. QTc ≥470 milliseconds calculated using Frediricia's Correction
    4. Current or history of pericardial effusion causing hemodynamic compromise
  • History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
  • Any positive test for HIV 1/2 antibodies and/or RNA.
  • Any positive test for hepatitis B virus(HBV) using HBV surface antigen (HBV sAG) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection.
  • 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 a live vaccine within 30 days of planned start of study therapy. a. 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.
  Contacts and Locations
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): NCT03220477


Contacts
Contact: Matthew Hellmann, MD 646-888-4863 hellmanm@mskcc.org
Contact: Charles Rudin, MD, PhD 646-888-4527

Locations
United States, Maryland
John Hopkins Medical Center Not yet recruiting
Baltimore, Maryland, United States, 21287
Contact: Jarushka Naidoo, M.B.B.Ch.    410-955-8933    jnaidoo1@jhmi.edu   
Principal Investigator: Stephen Baylin, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Matthew Hellmann, MD    646-888-4863      
Contact: Charles Rudin, MD, PhD    646-888-4527      
Principal Investigator: Matthew Hellmann, MD         
United States, Pennsylvania
Fox Chase Cancer Center Not yet recruiting
Philadelphia, Pennsylvania, United States, 19111-2497
Contact: Hossein Borghaei, MS, DO    888-369-2427      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Merck Sharp & Dohme Corp.
Astex Pharmaceuticals
Mirati Therapeutics Inc.
Investigators
Principal Investigator: Matthew Hellmann, MD Memorial Sloan Kettering Cancer Center
  More Information

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03220477     History of Changes
Other Study ID Numbers: 17-241
First Submitted: July 14, 2017
First Posted: July 18, 2017
Last Update Posted: November 17, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Memorial Sloan Kettering Cancer Center:
Pembrolizumab
guadecitabine
mocetinostat
17-241

Additional relevant MeSH terms:
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pembrolizumab
Azacitidine
Mocetinostat
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Histone Deacetylase Inhibitors