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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

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).

Condition or disease Intervention/treatment Phase
Esophageal Cancer Drug: Durvalumab Drug: Tremelimumab Drug: Oxaliplatin Drug: Capecitabine Radiation: Radiotherapy Drug: Paclitaxel Drug: Carboplatin Drug: 5-fluorouracil (5-FU) Drug: Leucovorin Drug: docetaxel Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2 Study of Anti-PD-L1 in Combination With Chemo(Radio)Therapy for Oesophageal Cancer
Actual Study Start Date : June 24, 2016
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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
Drug: Durvalumab
Other Names:
  • MEDI4736
  • Imfinzi

Drug: Oxaliplatin
IV administered Chemotherapy
Other Name: Eloxatin

Drug: Capecitabine
orally-administered chemotherapy
Other Name: Xeloda

Experimental: Durvalumab + tremelimumab and standard of care chemotherapy
Dose-escalation for Tremelimumab 37.5mg - 75mg + Durvalumab 750mg + Chemotherapy (Cohort A2).
Drug: Durvalumab
Other Names:
  • MEDI4736
  • Imfinzi

Drug: Tremelimumab
Drug: Oxaliplatin
IV administered Chemotherapy
Other Name: Eloxatin

Drug: Capecitabine
orally-administered chemotherapy
Other Name: Xeloda

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.
Drug: Durvalumab
Other Names:
  • MEDI4736
  • Imfinzi

Drug: Tremelimumab
Drug: Oxaliplatin
IV administered Chemotherapy
Other Name: Eloxatin

Drug: Capecitabine
orally-administered chemotherapy
Other Name: Xeloda

Experimental: Durvalumab, surgery and standard of care chemotherapy
Durvalumab 750mg + Chemotherapy (Cohort C)
Drug: Durvalumab
Other Names:
  • MEDI4736
  • Imfinzi

Drug: Oxaliplatin
IV administered Chemotherapy
Other Name: Eloxatin

Drug: Capecitabine
orally-administered chemotherapy
Other Name: Xeloda

Experimental: Durvalumab, surgery, standard of care chemo and radiotherapy
Durvalumab 750mg + Chemotherapy Radiotherapy (Cohort D)
Drug: Durvalumab
Other Names:
  • MEDI4736
  • Imfinzi

Radiation: Radiotherapy
Other Name: Radiation

Drug: Paclitaxel
IV administered Chemotherapy
Other Name: Taxol

Drug: Carboplatin
IV administered Chemotherapy
Other Name: Paraplatin

Experimental: Durvalumab, surgery, new standard of care chemotherapy C-FLOT
Durvalumab 750mg + Chemotherapy (Cohort C-FLOT)
Drug: Durvalumab
Other Names:
  • MEDI4736
  • Imfinzi

Drug: Oxaliplatin
IV administered Chemotherapy
Other Name: Eloxatin

Drug: 5-fluorouracil (5-FU)
IV administered Chemotherapy

Drug: Leucovorin
orally-administered chemo-protective agent

Drug: docetaxel
IV administered Chemotherapy
Other Name: Taxotere




Primary Outcome Measures :
  1. Number of subjects reporting Adverse Events [ Time Frame: up to 1 year ]
  2. Number of subjects experiencing a dose-limiting toxicity [ Time Frame: up to 10 weeks after the first dose of study medication ]
  3. Change from Baseline in laboratory evaluations [ Time Frame: Screening through 3 months after the last dose of study medication ]

Secondary Outcome Measures :
  1. Tumor response by irRECIST [ Time Frame: up to 12 months ]
  2. Progression Free Survival [ Time Frame: up to 36 months ]
  3. Overall Survival [ Time Frame: up to 36 months ]
  4. 1 year Survival Rate in subjects with operable oesophageal cancer [ Time Frame: up to 12 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02735239


Locations
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United Kingdom
Research Facility
Dundee, United Kingdom, DD1 9SY
Research Facility
Nottingham, United Kingdom, NG5 1PB
Research Facility
Oxford, United Kingdom, OX3 9DU
Research Facility
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
Ludwig Institute for Cancer Research
AstraZeneca
Investigators
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Study Chair: Mark Middleton University of Oxford, UK
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Responsible Party: Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier: NCT02735239    
Other Study ID Numbers: LUD2015-005
First Posted: April 12, 2016    Key Record Dates
Last Update Posted: February 18, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ludwig Institute for Cancer Research:
Oesophageal Cancer
Oesophageal adenocarcinoma
Oesophageal squamous cell carcinoma
Immunotherapy
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
Programmed cell death protein 1 (PD-1)
Programmed death ligand 1 (PD-L1)
Additional relevant MeSH terms:
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Leucovorin
Paclitaxel
Docetaxel
Carboplatin
Fluorouracil
Capecitabine
Oxaliplatin
Durvalumab
Tremelimumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances
Antineoplastic Agents, Immunological