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Study of Anti-PD-L1 in Combination With Chemo(Radio)Therapy for Oesophageal Cancer

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02735239
Recruitment Status : Active, not recruiting
First Posted : April 12, 2016
Last Update Posted : February 18, 2021
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Ludwig Institute for Cancer Research

Tracking Information
First Submitted Date  ICMJE March 17, 2016
First Posted Date  ICMJE April 12, 2016
Last Update Posted Date February 18, 2021
Actual Study Start Date  ICMJE June 24, 2016
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 11, 2016)
  • Number of subjects reporting Adverse Events [ Time Frame: up to 1 year ]
  • Number of subjects experiencing a dose-limiting toxicity [ Time Frame: up to 10 weeks after the first dose of study medication ]
  • Change from Baseline in laboratory evaluations [ Time Frame: Screening through 3 months after the last dose of study medication ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 11, 2016)
  • Tumor response by irRECIST [ Time Frame: up to 12 months ]
  • Progression Free Survival [ Time Frame: up to 36 months ]
  • Overall Survival [ Time Frame: up to 36 months ]
  • 1 year Survival Rate in subjects with operable oesophageal cancer [ Time Frame: up to 12 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Anti-PD-L1 in Combination With Chemo(Radio)Therapy for Oesophageal Cancer
Official Title  ICMJE Phase 1/2 Study of Anti-PD-L1 in Combination With Chemo(Radio)Therapy for Oesophageal Cancer
Brief Summary This is an open-label, Phase 1/2 study to evaluate the safety of durvalumab (MEDI4736) in combination with oxaliplatin/capecitabine chemotherapy in metastatic/locally advanced oesophageal cancer (OC) and with neoadjuvant chemo(radio)therapy before surgery in operable OC. The immunotherapy will be given for a 4-week period before starting the standard chemo(radio)therapy, continuing durvalumab treatment once the chemotherapy starts. The study will include 2 phases, a safety run-in Phase 1 (Cohorts A1 and A2) and an expansion Phase 2 (Cohorts B, C, C-FLOT, D).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Esophageal Cancer
Intervention  ICMJE
  • Drug: Durvalumab
    Other Names:
    • MEDI4736
    • Imfinzi
  • Drug: Tremelimumab
  • Drug: Oxaliplatin
    IV administered Chemotherapy
    Other Name: Eloxatin
  • Drug: Capecitabine
    orally-administered chemotherapy
    Other Name: Xeloda
  • Radiation: Radiotherapy
    Other Name: Radiation
  • Drug: Paclitaxel
    IV administered Chemotherapy
    Other Name: Taxol
  • Drug: Carboplatin
    IV administered Chemotherapy
    Other Name: Paraplatin
  • Drug: 5-fluorouracil (5-FU)
    IV administered Chemotherapy
  • Drug: Leucovorin
    orally-administered chemo-protective agent
  • Drug: docetaxel
    IV administered Chemotherapy
    Other Name: Taxotere
Study Arms  ICMJE
  • Experimental: Durvalumab and standard of care chemotherapy
    Phase 1 will evaluate the safety of durvalumab alone (Cohort A1) administered before chemotherapy (oxaliplatin + capecitabine) in subjects with metastatic or locally advanced Oesophageal Cancer + Chemotherapy
    Interventions:
    • Drug: Durvalumab
    • Drug: Oxaliplatin
    • Drug: Capecitabine
  • Experimental: Durvalumab + tremelimumab and standard of care chemotherapy
    Dose-escalation for Tremelimumab 37.5mg - 75mg + Durvalumab 750mg + Chemotherapy (Cohort A2).
    Interventions:
    • Drug: Durvalumab
    • Drug: Tremelimumab
    • Drug: Oxaliplatin
    • Drug: Capecitabine
  • Experimental: Recommended combination of doses from Cohort A1 or A2
    Subjects in Cohort B are subjects with metastatic/locally advanced Oesophageal Cancer. Subjects in Cohort B will receive the recommended combination dose from Cohort A1 (durvalumab alone administered before chemotherapy (oxaliplatin + capecitabine)) or A2 (Dose-escalation for Tremelimumab 37.5mg - 75mg + Durvalumab 750mg + Chemotherapy) and Chemotherapy.
    Interventions:
    • Drug: Durvalumab
    • Drug: Tremelimumab
    • Drug: Oxaliplatin
    • Drug: Capecitabine
  • Experimental: Durvalumab, surgery and standard of care chemotherapy
    Durvalumab 750mg + Chemotherapy (Cohort C)
    Interventions:
    • Drug: Durvalumab
    • Drug: Oxaliplatin
    • Drug: Capecitabine
  • Experimental: Durvalumab, surgery, standard of care chemo and radiotherapy
    Durvalumab 750mg + Chemotherapy Radiotherapy (Cohort D)
    Interventions:
    • Drug: Durvalumab
    • Radiation: Radiotherapy
    • Drug: Paclitaxel
    • Drug: Carboplatin
  • Experimental: Durvalumab, surgery, new standard of care chemotherapy C-FLOT
    Durvalumab 750mg + Chemotherapy (Cohort C-FLOT)
    Interventions:
    • Drug: Durvalumab
    • Drug: Oxaliplatin
    • Drug: 5-fluorouracil (5-FU)
    • Drug: Leucovorin
    • Drug: docetaxel
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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 11, 2016)
75
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2023
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histological diagnosis of oesophageal or gastrooesophageal cancer and have not received prior chemotherapy

    • Cohorts A and B - metastatic/locally advanced cancer
    • Cohorts C/C-FLOT and D/D2 - deemed suitable for surgery with curative intent
  2. Anticipated lifespan greater than 4 months
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  4. At the time of day 1 of the study, subjects with brain metastases must be asymptomatic for at least 4 weeks and:

    • at least 8 weeks without tumour progression after any whole brain radiotherapy
    • at least 4 weeks since craniotomy and resection or stereotactic radiosurgery
    • at least 3 weeks without new brain metastases as evidenced by MRI/CT
  5. Adequate normal organ and marrow function. Laboratory parameters for vital functions should be in the normal range. Laboratory abnormalities that are not clinically significant are generally permitted.
  6. Written informed consent obtained from the subject; subject been informed of other treatment options, and able to comply with study requirements
  7. Age 18 years or older.

Exclusion Criteria

  1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). Previous enrollment in the present study.
  2. Participation in another clinical study with an investigational product during the last 4 weeks
  3. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction
  4. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
  5. History of allogeneic organ transplant
  6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C, known immunodeficiency or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
  7. Known history of previous clinical diagnosis of tuberculosis
  8. History of pneumonitis or interstitial lung disease.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02735239
Other Study ID Numbers  ICMJE LUD2015-005
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ludwig Institute for Cancer Research
Study Sponsor  ICMJE Ludwig Institute for Cancer Research
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE
Study Chair: Mark Middleton University of Oxford, UK
PRS Account Ludwig Institute for Cancer Research
Verification Date February 2021

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