Clinical Trials /

Abemaciclib and Pembrolizumab in Locally Advanced Unresectable or Metastatic Gastroesophageal Adenocarcinoma: Big Ten Cancer Research Consortium BTCRC-GI18-149

NCT03997448

Description:

This study will test the combination of abemaciclib with pembrolizumab in patients with gastric, gastroesophageal junction, or esophageal adenocarcinoma that is metastatic or cannot be surgically removed, and who have progressed on, or were unable to tolerate, at least 2 earlier courses of treatment for their advanced disease.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Adenocarcinoma
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Abemaciclib and Pembrolizumab in Locally Advanced Unresectable or Metastatic Gastroesophageal Adenocarcinoma: Big Ten Cancer Research Consortium BTCRC-GI18-149
  • Official Title: Phase II Study of the Combination of Abemaciclib and Pembrolizumab in Locally Advanced Unresectable or Metastatic Gastroesophageal Adenocarcinoma: Big Ten Cancer Research Consortium BTCRC-GI18-149

Clinical Trial IDs

  • ORG STUDY ID: BTCRC-GI18-149
  • NCT ID: NCT03997448

Conditions

  • Gastroesophageal Cancer
  • Adenocarcinoma

Interventions

DrugSynonymsArms
PembrolizumabAbemaciclib and Pembrolizumab
AbemaciclibAbemaciclib and Pembrolizumab

Purpose

This study will test the combination of abemaciclib with pembrolizumab in patients with gastric, gastroesophageal junction, or esophageal adenocarcinoma that is metastatic or cannot be surgically removed, and who have progressed on, or were unable to tolerate, at least 2 earlier courses of treatment for their advanced disease.

Detailed Description

      This is a Phase II non-randomized, single arm, open label study of abemaciclib in combination
      with pembrolizumab in patients with unresectable or metastatic gastric, gastroesophageal
      junction, or esophageal adenocarcinoma who have received at least two lines of prior therapy.
      Treatment will be administered in 21-day cycles. Pembrolizumab will be administered
      intravenously (IV) at a dose of 200 mg on day 1 of each cycle. Abemaciclib will be taken
      orally twice a day on each day of the cycle, 150 mg per dose. Treatment will continue until
      disease progression or development of unacceptable toxicities.
    

Trial Arms

NameTypeDescriptionInterventions
Abemaciclib and PembrolizumabExperimentalAbemaciclib 150mg days 1-21, and Pembrolizumab 200mg IV, Day 1
  • Pembrolizumab
  • Abemaciclib

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with histologically confirmed metastatic or locally advanced unresectable
             gastric, gastroesophageal junction or esophageal adenocarcinoma.

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

          -  Age >= 18 years at the time of consent.

          -  Prior treatment with at least two lines of systemic therapy for advanced disease.
             Patients who have received neoadjuvant or adjuvant therapy or definitive
             chemoradiation and had recurrence during or within 6 months of completion of all
             treatments may count adjuvant therapy as one chemotherapy line.

          -  Presence of measurable disease based on RECIST 1.1 as determined by local site
             investigator/radiology assessment.

          -  ECOG PS 0-1.

          -  Patients must have discontinued all previous treatments for cancer (including
             cytotoxic chemotherapy, molecularly targeted therapy, radiotherapy, and
             investigational therapy).

          -  Patients who received chemotherapy must have recovered (CTCAE Grade ≤1) from the acute
             effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy.
             A washout period of at least 21 days is required between last systemic therapy dose
             and treatment initiation per protocol.

          -  A washout period of at least 14 days is required between end of radiotherapy and
             treatment initiation.

          -  The patient is able to swallow oral medications.

          -  Demonstrate adequate organ function as defined in the table in the protocol.

          -  Females of childbearing potential must have a negative serum pregnancy test within 7
             days prior to registration. NOTE: Females are considered of child bearing potential
             unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal
             ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least
             12 consecutive months.

          -  Females of childbearing potential must be willing to abstain from heterosexual
             activity or to use 2 forms of effective methods of contraception from the time of
             informed consent until 60 days after treatment discontinuation. The two contraception
             methods can be comprised of two barrier methods, or a barrier method plus a hormonal
             method.

          -  Men who are not surgically sterile (vasectomy) must agree to use an acceptable method
             of contraception. Male subjects with female sexual partners who are pregnant, possibly
             pregnant, or who could become pregnant during the study must agree to use condoms from
             the first dose of study drug through at least 60 days after the last dose of study
             drug. Total abstinence for the same time period is an acceptable alternative.

          -  As determined by the enrolling physician or protocol designee, ability of the subject
             to understand and comply with study procedures for the entire length of the study.

          -  Provided written informed consent and HIPAA authorization for release of personal
             health information, approved by an Institutional Review Board (IRB). NOTE: HIPAA
             authorization may be included in the informed consent or obtained separately.

        Exclusion Criteria:

          -  Active autoimmune disease that has required systemic treatment in 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.

          -  History of prior therapy with CDK4 or CDK6 inhibitors or prior immune checkpoint
             inhibitors.

          -  Patients with known microsatellite instability will be excluded.

          -  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. The use of physiologic doses of corticosteroids may be approved after
             consultation with the study PI.

          -  Serious preexisting medical condition(s) that would preclude participation in this
             study (for example, interstitial lung disease, severe dyspnea at rest or requiring
             oxygen therapy, history of major surgical resection involving the stomach or small
             bowel, or a preexisting chronic condition resulting in baseline Grade 2 or higher
             diarrhea).

          -  Symptomatic central nervous system metastasis. Screening of asymptomatic patients is
             not required for enrollment.

          -  Personal history of any of the following conditions: syncope of cardiovascular
             etiology, ventricular arrhythmia of pathological origin (including, but not limited
             to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.

          -  Known additional malignancy that progressed or required active treatment within the
             last 2 years. Exceptions include curatively treated basal cell and squamous cell
             carcinoma of the skin, curatively resected in situ cervical and/or breast cancers, in
             situ or intramucosal pharyngeal cancer, and Gleason 6 prostate cancer with PSA <10.

          -  Patients who have received a live vaccine within 30 days of planned start of
             pembrolizumab.

        Note: The killed virus vaccines used for seasonal influenza vaccines for injection are
        allowed; however intranasal influenza vaccines (e.g., FluMist®) are live attenuated
        vaccines, and are not allowed.

          -  History of (non-infectious) pneumonitis that required steroids or current pneumonitis.

          -  Active infection requiring systemic therapy.

          -  Patients who are pregnant or breastfeeding or expecting to conceive or father children
             within the projected duration of the trial, starting with the screening visit through
             60 days after the last dose of pembrolizumab or abemaciclib. (NOTE: breast milk cannot
             be stored for future use while the mother is being treated on study.)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival
Time Frame:24 months
Safety Issue:
Description:PFS is defined as the time of treatment initiation until the criteria for disease progression per RECIST1.1 are met or until the date of a death event (any cause).

Secondary Outcome Measures

Measure:Progression-Free Survival Rate at 6 Months
Time Frame:6 Months
Safety Issue:
Description:PFS is defined as the percent of patients without a progression (or death event) at month 6 after treatment initiation.
Measure:Disease Control Rate
Time Frame:24 Months
Safety Issue:
Description:DCR is defined as percent of patients with stable disease, partial response and complete response after treatment initiation per RECIST 1.1 and irRECIST.
Measure:Overall Survival
Time Frame:24 Months
Safety Issue:
Description:OS is defined as the time of treatment initiation until death from any cause.
Measure:Objective Response Rate
Time Frame:24 Months
Safety Issue:
Description:ORR as measured as percent of patients who achieved objective response per RECIST 1.1 and irRECIST criteria while on treatment
Measure:Summarize Adverse Events
Time Frame:24 Months
Safety Issue:
Description:All adverse events summarized and assessed by NCI CTCAE version 5

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Nataliya Uboha

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