Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Perioperative mFOLFOX Plus Pembrolizumab in Gastroesophageal Junction (GEJ) and Stomach Adenocarcinoma

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.
 
ClinicalTrials.gov Identifier: NCT03488667
Recruitment Status : Recruiting
First Posted : April 5, 2018
Last Update Posted : July 15, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of Kansas Medical Center

Tracking Information
First Submitted Date  ICMJE March 28, 2018
First Posted Date  ICMJE April 5, 2018
Last Update Posted Date July 15, 2019
Actual Study Start Date  ICMJE June 27, 2018
Estimated Primary Completion Date April 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 28, 2018)
  • Pathological response rate (ypRR) [ Time Frame: 10-14 weeks ]
    Number of participants with ypRR after neoadjuvant therapy. Will be assessed on the surgical resection specimen after neoadjuvant therapy, using Haemotoxylin and Eosin (H&E) staining and evaluated using Tumor Regression Score.
  • Number of Adverse Events related to toxicity. [ Time Frame: up to 14 months ]
    Number of participants with adverse events related to toxicity. Evaluated using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Participants will be followed for adverse event monitoring through the final safety follow up visit or until study discontinuation/disease progression, whichever occurs first.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03488667 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 5, 2018)
  • Objective response rate (ORR) [ Time Frame: 12 months ]
    Number of participants with ORR (partial response and complete response) at 12 months. Evaluated using RECIST v1.1
  • Disease Free Survivial (DFS) [ Time Frame: 12 months ]
    Number of participants with DFS. Evaluated using computed tomography (CT).
  • Overall Survival (OS) [ Time Frame: 12 months ]
    Number of participants with OS.
  • PET response rate after completion of neo-adjuvant therapy. [ Time Frame: 10 weeks ]
    Evaluated using Positron emission tomography scan & computed tomography (PET-CT)
  • Programmed cell death ligand 1 (PD-L1) expression in tumor cells [ Time Frame: baseline and between 16-21 weeks ]
    Change in PD-L1 expression on the surface and in the nucleus of the tumor cells over treatment will be related to complete pathological response (ypCR) by means of logistic regression. Evaluated by immunohistochemistry (IHC). Participants will be evaluated at baseline and reevaluated 2-4 weeks after surgery (for those participants who develop complications from surgery, the revaluation time frame may be extended to 7 weeks).
Original Secondary Outcome Measures  ICMJE
 (submitted: March 28, 2018)
  • Objective response rate (ORR) [ Time Frame: 12 months ]
    Number of participants with ORR (partial response and complete response) at 12 months. Evaluated using RECIST v1.1
  • Disease Free Survivial (DFS) [ Time Frame: 12 months ]
    Number of participants with DFS. Evaluated using computed tomography (CT).
  • Overall Survival (OS) [ Time Frame: 12 months ]
    Number of participants with OS.
  • PET response rate after completion of neo-adjuvant therapy. [ Time Frame: 10 weeks ]
    Evaluated using Positron emission tomography scan & computed tomography (PET-CT)
  • Programmed cell death ligand 1 (PD-L1) expression in tumor cells [ Time Frame: baseline and between 16-21 weeks ]
    Change in PD-L1 expression on the surface and in the nucleus of the tumor cells over treatment will be related to ypCR by means of logistic regression. Evaluated by immunohistochemistry (IHC). Participants will be evaluated at baseline and reevaluated 2-4 weeks after surgery (for those participants who develop complications from surgery, the revaluation time frame may be extended to 7 weeks).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Perioperative mFOLFOX Plus Pembrolizumab in Gastroesophageal Junction (GEJ) and Stomach Adenocarcinoma
Official Title  ICMJE A Phase II Study of Perioperative mFOLFOX (Fluorouracil, Leucovorin, and Oxaliplatin) Chemotherapy Plus Pembrolizumab(MK-3475) Combination in Patients With Potentially Resectable Adenocarcinoma of the Gastroesophageal Junction (GEJ) and Stomach (MISP #52216)
Brief Summary To evaluate the antitumor activity and safety/tolerability of the combination (mFOLFOX + Pembrolizumab) in patients with potentially resectable adenocarcinoma of the Gastroesophageal Junction (GEJ) and stomach.
Detailed Description

This study will evaluate the efficacy and safety of perioperative mFOLFOX plus Pembrolizumab combination regimen in participants with potentially resectable adenocarcinoma of the GEJ and stomach.

  • The study is a non-randomized, open-label, single-arm phase II study.
  • The enrolled participants will receive neoadjuvant combination of mFOLFOX every 2 weeks for 4 doses (on Days 1, 15, 29, 43) and Pembrolizumab every 3 weeks for 3 doses (on Days 1, 22, 43).
  • Serious adverse events (SAEs) will be assessed on an ongoing basis using CTCAE v4.0, and the Thall, Simon, and Estey's design to monitor the efficacy and toxicity continuously together.
  • Repeat PET-CT will be obtained approximately 2-3 weeks after completion of neoadjuvant combination therapy.
  • If no evidence of metastatic disease on PET-CT, participants will undergo potentially curative surgical resection 4-6 weeks after completion of neoadjuvant combination therapy. This will be followed by adjuvant combination therapy (to be started 6-8 weeks after surgery) consisting of mFOLFOX every 2 weeks for additional 4 doses (total 4 months of therapy) plus Pembrolizumab every 3 weeks for additional 12 doses (total 1 year of therapy). If there is evidence of metastatic disease on PET-CT, participant will come off the study (i.e., will not undergo surgical resection and adjuvant therapy).
  • Participants will continue to receive treatment until either one of the following occurs: completion of adjuvant therapy, development of radiographically confirmed progression, participant withdraws consent, intercurrent illness that prevents further administration of treatment, or sponsor-investigator decides to withdraw the participant.
  • Efficacy outcomes during the adjuvant chemotherapy phase will be determined by radiologic measurements by CT using RECIST v1.1. Assessment of response will be performed every 3 months for the first year and as per the standard institutional guidelines thereafter.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Gastro Esophageal Junction Cancer
  • Stomach Cancer
  • Adenocarcinoma
Intervention  ICMJE
  • Drug: Neoadjuvant Treatment - mFOLFOX6 & Pembrolizumab
    Pembrolizumab, mFOLFOX Chemotherapy
  • Drug: Adjuvant Treatment - mFOLFOX & Pembrolizumab
    Pembrolizumab, mFOLFOX Chemotherapy
Study Arms  ICMJE Experimental: mFOLFOX6 (Leucovorin-Fluorouracil-Oxaliplatin) + Pembrolizumab

Drug: Pembrolizumab Dose: 200 mg Dose Frequency: Every three weeks (Q3W) Route: Intravenous (IV) infusion

Drug: Oxaliplatin Dose: 85 milligrams per meter squared (mg/m2) Dose Frequency: Every 2 weeks (Q2W) Route: IV infusion

Drug: Leucovorin Dose: 400 mg/m2 Dose Frequency: Q2W Route: IV infusion

Drug: Fluorouracil Dose: 400 mg/m2 Dose Frequency: Q2W Route: IV bolus

Drug: Fluorouracil Dose: 2,400 mg/m2 Dose Frequency: Q2W Route: IV continuous 46-hour infusion

Pembrolizumab will be administered at a fixed dose of 200 mg IV over 30 minutes every 3 weeks. Participants will receive 3 doses of the drug on Days 1, 22, 43 during the neoadjuvant phase of the study, and 12 doses of the drug on Days 1, 22, 43 during the adjuvant phase of the study (total 15 doses). Participants will receive 4 doses of mFOLFOX6 regimen on Days 1, 15, 29, 43 during the neoadjuvant phase of the study, and 4 doses during the adjuvant phase of the study (total 8 doses).

Interventions:
  • Drug: Neoadjuvant Treatment - mFOLFOX6 & Pembrolizumab
  • Drug: Adjuvant Treatment - mFOLFOX & Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 28, 2018)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 30, 2021
Estimated Primary Completion Date April 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male/female participants who are 18 - 75 years of age on the day of signing informed consent with histologically or cytologically confirmed diagnosis of adenocarcinoma of the gastroesophegeal junction (GEJ) or stomach will be enrolled in this study.
  2. Have newly diagnosed localized or locally advanced, potentially resectable disease without any prior systemic chemotherapy.
  3. Have no evidence of distant metastases.
  4. Be eligible and reasonably fit to undergo potentially curative resection

    Male participants:

  5. A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.

    Female participants:

  6. Female participants of childbearing potential must have a negative serum pregnancy within 72 hours prior to enrollment.
  7. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

    1. Not a woman of childbearing potential (WOCBP) OR
    2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at 120 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.
  8. The participant (or legally authorized representative, if applicable) must be willing and able to provide written informed consent for the trial.
  9. Have evaluable disease . Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  10. Have pre-resection tissue available.
  11. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion.
  12. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  13. Have adequate organ function.
  14. Be willing to provide blood and tissue samples for research purposes.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

  1. A WOCBP who has a positive serum pregnancy test within 72 hours prior to enrollment on study.
  2. Has received prior therapy with an anti-PD-1 (Programmed death-1), anti-PD-L1 (programmed death ligand-1), or anti PD L2 (programmed death ligand-2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.
  3. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study enrollment.
  4. Has received prior chemotherapy (including investigational agents) for any malignant disorder, thoracic radiation therapy or prior surgical resection of an esophagogastric tumor.

    a. Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.

  5. Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
  6. Has biopsy-proven invasion of tracheobronchial tree or tracheo-esophageal fistula.
  7. Has distant metastatic disease on imaging or staging laparoscopy at the time of study entry.
  8. Has a known history of active TB (tuberculosis)
  9. Hypersensitivity to pembrolizumab or any of its excipients.
  10. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier.
  11. Clinically significant peripheral neuropathy at the time of study entry.
  12. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed.
  13. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.

    a. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.

  14. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
  15. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  16. Has active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically serious autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Participants with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Participants that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Participants with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study.
  17. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  18. Has an active infection requiring systemic therapy.
  19. Has a known history of Human Immunodeficiency Virus (HIV).
  20. Has a known history of Hepatitis B or known active Hepatitis C virus infection. Note: testing for Hepatitis B and Hepatitis C is required only if mandated by local health authority.
  21. Inoperable on the basis of co-existent medical problems.
  22. Non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude any of the study drugs.
  23. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  24. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  25. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kerry Hepler, RN 913-945-7552 ctnursenav@kumc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03488667
Other Study ID Numbers  ICMJE IIT-2017-PeriopmFOLFOXPem
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party University of Kansas Medical Center
Study Sponsor  ICMJE University of Kansas Medical Center
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Weijing Sun, MD, FACP The University of Kansas - Cancer Center
PRS Account University of Kansas Medical Center
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP