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Trial record 3 of 4 for:    miksad

Pembrolizumab in Refractory Advanced Esophageal Cancer

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified December 2016 by Dana-Farber Cancer Institute
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Peter C. Enzinger, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT02971956
First received: November 21, 2016
Last updated: December 7, 2016
Last verified: December 2016
  Purpose

This research study is studying a targeted therapy as a possible treatment for advanced esophageal cancer.

The study intervention involved in this study is:

-Pembrolizumab


Condition Intervention Phase
Esophageal Cancer
Squamous Cell Esophagus Cancer
Adenocarcinoma Esophagus
Drug: Pembrolizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Pembrolizumab in Refractory Advanced Esophageal Cancer

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Major Response Rate (CR + PR) Of Patients With Refractory Esophageal Adenocarcinoma To Pembrolizumab [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Evaluate the response rate, by irRECIST, of pembrolizumab in refractory, advanced esophageal adenocarcinoma patients.


Secondary Outcome Measures:
  • Complete Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Evaluate the response rate, by irRECIST, of pembrolizumab in refractory, advanced esophageal adenocarcinoma patients.

  • Partial Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Evaluate the response rate, by irRECIST, of pembrolizumab in refractory, advanced esophageal adenocarcinoma patients.

  • Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Overall Survival (OS) is defined as the time from registration to death due to any cause, or censored at date last known alive. OS will be measured by the Method of Kaplan and Meier.

  • Progression-Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Progression-Free Survival (PFS) is defined as the time from registration to the earlier of progression or death due to any cause. PFS will be measured by the Method of Kaplan and Meier.

  • Evaluate The Durability Of Pembrolizumab Response In Advanced Esophageal Cancer Patients [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Evaluate the durability of pembrolizumab response in advanced esophageal cancer patients by measuring median overall survival and median progression free survival.Progression-free Survival (PFS) and Overall Survival (OS) as measured by the Method of Kaplan and Meier.

  • Evaluate The Safety And Tolerability Of Pembrolizumab 200 Mg, Administered Every Three Weeks, In Advanced Esophageal Cancer. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Evaluate the safety and tolerability of pembrolizumab 200 mg, administered every three weeks, in advanced esophageal cancer. A full physical exam will be performed before the start of each cycle. Adverse events, ECOG performance status, and laboratory assessments will be performed regularly.


Estimated Enrollment: 50
Study Start Date: December 2016
Estimated Study Completion Date: June 2024
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pembrolizumab
  • Pembrolizumab administered every three weeks
  • Pembrolizumab will be given intravenously
Drug: Pembrolizumab
Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
Other Name: Keytruda

Detailed Description:

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved Pembrolizumab for the participant specific disease but it has been approved for other uses.

Pembrolizumab, also known as KEYTRUDA or MK-3475, is approved in the USA and several other countries to treat other types of diseases.

The goal of this research study is to

-Evaluate the safety and efficacy of pembrolizumab in participants with advanced esophageal cancer that have not responded to standard treatment.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed, measurable, unresectable adenocarcinoma or squamous cell carcinoma of the esophagus. For the purposes of this study, undifferentiated carcinomas or adenosquamous carcinomas will be categorized as adenocarcinomas.
  • The primary tumor must originate in the esophagus. Tumors that involve the GE junction must meet Sievert Type 1 criteria: "Adenocarcinoma of the distal oesophagus which usually arises from an area with specialized intestinal metaplasia of the oesophagus (i.e. Barrett's oesophagus) and which may infiltrate the oesophagogastric junction from above." For the purposes of this protocol, this will be interpreted as: greater than 50% of the tumor must be above the GE junction or, alternatively, the tumor must involve the GE junction and arise in the setting of biopsy-documented Barrett's esophagus (specialized intestinal metaplasia).
  • Patients must have received at least one prior therapy for unresectable disease. Patients with recurrence within 6 months of completion of neoadjuvant or adjuvant therapy may be considered as having received one prior therapy for unresectable disease.
  • Be 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 irRECIST.
  • Be willing to provide tissue from a newly obtained biopsy of a tumor lesion, most commonly an EGD biopsy from the esophagus. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor. Please note, patients may not initiate therapy until the biopsy specimen is received at the Dana-Farber Cancer Institute.
  • The first 15 patients with adenocarcinoma will be offered an optional tumor biopsy (typically EGD biopsy) at 8 weeks. Starting with adenocarcinoma patient #16, patients must have an accessible tumor and must agree to tumor biopsy at 8 weeks; this will continue to be mandatory until a total of 20 patients have undergone biopsy at 8 weeks.
  • Have a performance status of 0 or 1 on the ECOG Performance Scale (Appendix A).
  • Female subject of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Female subjects of childbearing potential must 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 (Reference Section 6.3.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • Demonstrate adequate organ function as defined below, all screening labs should be performed within 10 days of treatment initiation.

Hematological

  • Absolute neutrophil count (ANC) ≥1,500 /mcL
  • Platelets ≥80,000 / mcL
  • Hemoglobin ≥8.5 g/dL or ≥5.6 mmol/L

    -Renal

  • Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured creatinine clearance ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCL) Creatinine clearance should be calculated per institutional standard.

    -Hepatic

  • Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
  • AST (SGOT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
  • ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
  • Albumin > 2.8 mg/dL

    -Coagulation

  • International Normalized Ratio (INR) OR Prothrombin Time (PT) ≤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
  • 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

Exclusion Criteria:

  • 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. Subjects requiring systemic steroids are excluded from the trial. The use of physiologic doses of corticosteroids may be approved after discussion with the sponsor.
  • Has a known history of active TB (Bacillus Tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • 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, 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: Subjects with ≤ Grade 2 neuropathy and alopecia are an exception to this criterion and may qualify for the study.
    • Note: If subject received major surgery, they must wait ≥ 3 weeks prior to starting study treatment. 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. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has an active infection requiring systemic therapy.
  • Patients that require supplemental oxygen are excluded.
  • 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 prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02971956

Contacts
Contact: Peter C. Enzinger, MD 617-632-6855 Peter_Enzinger@dfci.harvard.edu

Locations
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Justin Gainor, MD    617-724-4000      
Principal Investigator: Justin Gainor, MD         
Beth Israel Deaconess Medical Center Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Rebecca Miksad, MD    617-667-4827      
Principal Investigator: Rebecca Miksad, MD         
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Peter C. Enzinger, MD    617-632-6855    Peter_Enzinger@dfci.harvard.edu   
Principal Investigator: Peter C. Enzinger, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Peter C. Enzinger, MD Dana-Farber Cancer Institute
  More Information

Responsible Party: Peter C. Enzinger, MD, Peter C. Enzinger MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02971956     History of Changes
Other Study ID Numbers: 16-293 
Study First Received: November 21, 2016
Last Updated: December 7, 2016
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Dana-Farber Cancer Institute:
Esophageal Cancer

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Neoplasms, Squamous Cell
Pembrolizumab
Antineoplastic Agents

ClinicalTrials.gov processed this record on December 08, 2016