Clinical Trials /

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

NCT03220477

Description:

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.

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab (Immunotherapy Drug) in Combination With Guadecitabine and Mocetinostat (Epigenetic Drugs) for Patients With Advanced Lung Cancer.
  • Official Title: Phase I/Ib Study of Combined Pembrolizumab Plus Guadecitabine and Mocetinostat for Patients With Advanced NSCLC (DOSE SELECTION)

Clinical Trial IDs

  • ORG STUDY ID: 17-241
  • NCT ID: NCT03220477

Conditions

  • Lung Cancer

Interventions

DrugSynonymsArms
Pembrolizumabpembrolizumab plus guadecitabine and mocetinostat
Guadecitabinepembrolizumab plus guadecitabine and mocetinostat
Mocetinostatpembrolizumab plus guadecitabine and mocetinostat

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.

Trial Arms

NameTypeDescriptionInterventions
pembrolizumab plus guadecitabine and mocetinostatExperimentalPembrolizumab given IV; guadecitabine given SQ, mocetinostat given PO.
  • Pembrolizumab
  • Guadecitabine
  • Mocetinostat

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:number of patients with adverse events
Time Frame:1 year
Safety Issue:
Description: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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Pembrolizumab
  • guadecitabine
  • mocetinostat
  • 17-241

Last Updated

August 8, 2017