Clinical Trials /

Guadecitabine and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

NCT02901899

Description:

The purpose of this study is to look at how patients respond to treatment with guadecitabine and pembrolizumab. The researchers will also be looking at the amount of time it takes for cancer to get worse when participants take the study drugs. All participants will be treated with guadecitabine and pembrolizumab. Guadecitabine interferes with the cancer cells' DNA and can increase the production of certain proteins, making cancer cells more recognizable by the immune system. Pembrolizumab helps your immune system to kill cancer cells. Thus the combination of guadecitabine and pembrolizumab may increase the ability of the immune system to eliminate cancer cells. Researchers want to find out whether the combination of guadecitabine and pembrolizumab is effective in treating ovarian cancer that has not responded to traditional chemotherapy. Participants will keep receiving treatment until their cancer gets worse, they have side effects, or they decide they don't want to receive the treatment anymore. After stopping treatment, the study doctor will watch participants for side effects and follow their condition every 6-12 weeks. The study aims to keep track of participants' medical conditions for the rest of their lives. This helps us look at the long-term effects of the study drugs.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Guadecitabine and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
  • Official Title: An Open Label Phase II Trial of Guadecitabine and Pembrolizumab in Platinum Resistant Recurrent Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: NU 16G03
  • SECONDARY ID: STU00203494
  • SECONDARY ID: NU 16G03
  • SECONDARY ID: P30CA060553
  • SECONDARY ID: NCI-2016-01296
  • NCT ID: NCT02901899

Conditions

  • Recurrent Fallopian Tube Carcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma

Interventions

DrugSynonymsArms
GuadecitabineDNMT inhibitor SGI-110, S110, SGI-110Treatment (guadecitabine, pembrolizumab)
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (guadecitabine, pembrolizumab)

Purpose

The purpose of this study is to look at how patients respond to treatment with guadecitabine and pembrolizumab. The researchers will also be looking at the amount of time it takes for cancer to get worse when participants take the study drugs. All participants will be treated with guadecitabine and pembrolizumab. Guadecitabine interferes with the cancer cells' DNA and can increase the production of certain proteins, making cancer cells more recognizable by the immune system. Pembrolizumab helps your immune system to kill cancer cells. Thus the combination of guadecitabine and pembrolizumab may increase the ability of the immune system to eliminate cancer cells. Researchers want to find out whether the combination of guadecitabine and pembrolizumab is effective in treating ovarian cancer that has not responded to traditional chemotherapy. Participants will keep receiving treatment until their cancer gets worse, they have side effects, or they decide they don't want to receive the treatment anymore. After stopping treatment, the study doctor will watch participants for side effects and follow their condition every 6-12 weeks. The study aims to keep track of participants' medical conditions for the rest of their lives. This helps us look at the long-term effects of the study drugs.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Measure objective response rate (RR) to guadecitabine and pembrolizumab in subjects with
      recurrent platinum resistant ovarian cancer (OC).

      SECONDARY OBJECTIVES:

      I. Measure progression free survival (PFS) for the combination of guadecitabine and
      pembrolizumab.

      II. Progression free survival (PFS). III. Measure clinical benefit rate (CBR) for the
      combination of guadecitabine and pembrolizumab.

      IV. Measure toxicity profiles to the combination of guadecitabine and pembrolizumab.

      TERTIARY OBJECTIVES:

      I. NY-ESO-1 and MAGE antigens' promoter methylation (pyrosequencing) and messenger
      ribonucleic acid (mRNA) expression levels (quantitative reverse transcriptase-polymerase
      chain reaction [RT-PCR]) will be measured before and after treatment in deoxyribonucleic
      acid (DNA) (plasma and/or tumor biopsies) and ribonucleic acid (RNA) (tumor biopsies),
      respectively.

      II. Cytokine response (IFN gamma IL2, IL6, IL10, TNF alpha) will be measured in plasma by
      enzyme-linked immunosorbent assay (ELISA).

      III. Measure LINE 1 methylation in DNA extracted from peripheral blood mononuclear cells
      (PBMCs) (measured on days 1 and 5 of cycles 1 and 2).

      IV. Expression of the PD-L1 ligand will be measured by immunohistochemistry (IHC) in
      archival tumors.

      V. Tumor infiltrating lymphocytes (TILs) will be quantified in tumor biopsies before and
      after treatment (IHC).

      OUTLINE:

      Patients receive guadecitabine subcutaneously (SC) on days 1-4 and pembrolizumab
      intravenously (IV) over 30 minutes on day 5. Courses repeat every 21 days in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days, every 6 weeks for
      1 year, and then every 9 weeks and, once a subject experiences confirmed disease progression
      or starts a new anticancer therapy, every 3 months thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (guadecitabine, pembrolizumab)ExperimentalPatients receive guadecitabine SC on days 1-4 and pembrolizumab IV over 30 minutes on day 5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Guadecitabine

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have a histological or cytological evidence/confirmation of recurrent
             epithelial ovarian cancer, primary peritoneal carcinomatosis, or fallopian tube
             cancer

          -  Patients must have measurable disease according to Response Evaluation Criteria in
             Solid Tumors (RECIST) 1.1 within 28 days prior to registration

          -  Prior therapy allowed:

               -  At least one and no more than 3 platinum based chemotherapy regimens

               -  Up to 2 non-platinum, cytotoxic regimen

               -  There is no limit on use of prior biological therapies (hormonal or targeted
                  therapy)

               -  NOTE: Prior immunotherapy is not allowed

          -  Patients must exhibit an Eastern Cooperative Oncology Group (ECOG), performance
             status of 0-1 within 14 days prior to registration

          -  Demonstrate adequate organ function as defined below; all screening labs to be
             obtained within 14 days prior to treatment initiation:

          -  Absolute neutrophil count (ANC) >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (without transfusion or growth factor
             support/erythropoietin [EPO] dependency)

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

          -  Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total
             bilirubin levels > 1.5 ULN

          -  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 liver metastases

          -  Albumin >= 2.5 mg/dL

          -  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

          -  Be willing to allow the use of archival formalin-fixed paraffin-embedded tumor tissue
             for correlative analyses

               -  Note: The archived tumor tissue specimens may be from prior surgery or from
                  prior diagnostic biopsy of primary or metastatic tumor specimen; unavailability
                  of archived tissue will not render subject ineligible for study

          -  Be willing and able to undergo a core or excisional tumor biopsy according to
             institutional standards (guided visually or by computed tomography [CT] or
             ultrasound), paracentesis, or thoracentesis for tumor cells

               -  Note: This is to be done prior to treatment at cycle 1 day 1 (C1D1) and
                  post-treatment (cycle 2 day 8), if this is clinically and safely feasible to do
                  so; this will allow the use of this freshly obtained tissue for correlative
                  analyses in the study

          -  Females of child-bearing potential (FOCBP) must agree to use adequate contraception
             prior to registration, for the duration of study participation, and for 120 days
             following completion of therapy; should a female patient become pregnant or suspect
             she is pregnant while participating in this study, she should inform her treating
             physician immediately

               -  NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a
                  tubal ligation, or remaining celibate by choice) who meets the following
                  criteria:

                    -  Has not undergone a hysterectomy or bilateral oophorectomy

                    -  Has had menses at any time in the preceding 12 consecutive months (and
                       therefore has not been naturally postmenopausal for > 12 months)

          -  FOCBP must have a negative pregnancy test within 7 days prior to registration on
             study

          -  Patients must have the ability to understand and the willingness to sign a written
             informed consent prior to registration on study

        Exclusion Criteria:

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 14 days prior to registration or who has not recovered (i.e., =< grade 1 or at
             baseline) from adverse events due to a previously administered agent

               -  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 had a prior anti-cancer monoclonal antibody (mAb) within 28 days prior to
             registration or who has not recovered (i.e., =< grade 1 or at baseline) from adverse
             events due to agents administered more than 4 weeks earlier

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 28 days registration

          -  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 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; subjects with previously treated brain metastases may participate
             provided they are stable (without evidence of progression by imaging for at least 28
             days prior to registration 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; this exception does not include
             carcinomatous meningitis which is excluded regardless of clinical stability

          -  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 (e.g. thyroxine, insulin, or
             physiologic corticosteroid replacement therapy for adrenal or pituitary
             insufficiency, etc.) is not considered a form of systemic treatment

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent; please
             contact the principal investigator for further clarification if needed

          -  Hypersensitivity to pembrolizumab or any of its excipients

          -  Has a known history of active TB (Bacillus tuberculosis)

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

          -  Has a known history of hepatitis B and/or hepatitis C infection

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

          -  Has an active infection requiring systemic therapy within 3 days of registration
             (NOTE: except for uncomplicated urinary tract infection [UTI])

          -  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

          -  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

          -  Female patients who are pregnant or nursing, or expecting to conceive 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; subjects should not breast
             feed within 120 days of completing the trial

          -  Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or
             child) who is investigational site or sponsor staff directly involved with this
             trial, unless prospective Institutional Review Board (IRB) approval (by chair or
             designee) is given allowing exception to this criterion for a specific subject
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to 3 years
Safety Issue:
Description:Imaging scans will be assessed using the Immune Related Response Criteria (irRC) to measure ORR to guadecitabine and pembrolizumab in patients with recurrent platinum resistant Ovarian Cancer.

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:Up to 3 years
Safety Issue:
Description:Measure PFS for the combination of guadecitabine and pembrolizumab as evaluated by RECIST v 1.1 assessed from first dose of study treatment until disease progression or death from any cause, assessed for up to 3 years.
Measure:Clinical Benefit Rate (CBR)
Time Frame:Up to 3 years
Safety Issue:
Description:CBR for the combination of guadecitabine and pembrolizumab will be defined according to response assessment criteria that evaluates imaging scans.
Measure:Incidence of Adverse Events
Time Frame:Up to 3 years
Safety Issue:
Description:Assess the toxicity of guadecitabine and pembrolizumab by measuring the number, type, grade, severity, and frequency of adverse events according to the National Cancer Institute Common Terminology Criteria Adverse events (CTCAE) v 4.03.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Northwestern University

Last Updated

April 5, 2017