Study of Anti-PD-L1 in Combination With Chemo(Radio)Therapy for Oesophageal Cancer
Phase 1/2 Study of Anti-PD-L1 in Combination With Chemo(Radio)Therapy for Oesophageal Cancer
3 other identifiers
interventional
73
1 country
4
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/D2).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2016
Longer than P75 for phase_1
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 17, 2016
CompletedFirst Posted
Study publicly available on registry
April 12, 2016
CompletedStudy Start
First participant enrolled
June 24, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 16, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
June 16, 2022
CompletedResults Posted
Study results publicly available
March 22, 2024
CompletedMarch 22, 2024
September 1, 2023
6 years
March 17, 2016
November 1, 2022
September 12, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs)
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) were reported based on clinical laboratory tests, vital signs, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through 110 days after the last dose of study treatment. Treatment-emergent AEs were those that occurred or worsened after administration of the first dose of study treatment. In Cohorts A1, A2 and B, 12, 5 and 7 subjects, respectively, were monitored for dose limiting toxicities (DLTs) during the first 10 weeks of treatment (DLT evaluation period).
up to 1 year
Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), and in Cycles 1, 3, 5 and 6 in Cohorts A1, A2 and B. In the other cohorts, tumor response was assessed at baseline, post-surgery and 14 days after the last dose. In Cohorts C-FLOT and D, an additional assessment was done prior to surgery and in Cohorts C and D, an additional assessment was done in Cycle 3. Per irRECIST, measurable lesions are categorized as follows: Immune-related Complete Response (irCR): Complete disappearance of all target lesions; Immune-related Partial Response (irPR): ≥ 30% decrease from baseline in the Total Measurable Tumor Burden (TMTB); Immune-related Progressive Disease (irPD): ≥ 20% increase from nadir in TMTB; Immune-related Stable Disease (irSD): not meeting above criteria; irNon-CR/Non-PD: irNon-CR/Non-PD is preferred over SD when no lesions can be measured.
up to 1 year
Secondary Outcomes (5)
Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
Up to 23 weeks
Median Progression-free Survival (PFS) by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method
Up to 3 years
Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method
Up to 3 years
One Year Survival Rate in Subjects With Operable OC
up to 12 months
Overall Response Prior to Surgery in Operable OC (Cohorts C, C-FLOT and D/D2) Using Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST)
Up to 7months
Study Arms (6)
Cohort A1: Metastatic/locally advanced OC, Durva + Chemotherapy (Chemo)
EXPERIMENTALDurvalumab (750 mg IV every two weeks \[Q2W\]) was to be given for up to 11 doses. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
Cohort A2: Metastatic/locally advanced OC, Durva, Treme + Chemo
EXPERIMENTALDurvalumab (750 mg IV Q2W) was to be given for up to 11 doses. One dose of tremelimumab (37.5 mg IV) was given on the same day as the first dose of durvalumab. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
Cohort B: Metastatic/locally advanced OC, Durva, Treme + Chemo
EXPERIMENTALDurvalumab (750 mg IV Q2W) was to be given for up to 11 doses. One dose of tremelimumab (75 mg IV) was given on the same day as the first dose of durvalumab. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
Cohort C: Operable OC; Durva + Chemo
EXPERIMENTALDurvalumab (750 mg IV Q2W) was to be given for up to 5 doses. Two cycles of neoadjuvant oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy were to be administered before surgery. Subjects were to undergo surgery 6 to 8 weeks after completing chemotherapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions) once recovered from surgery, provided that this was within 3 months of surgery.
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy
EXPERIMENTALDurvalumab (750 mg IV Q2W) was to be given for up to 6 doses. Two cycles of neoadjuvant 5-fluorouracil (5-FU) (2600 mg/m\^2 24-hr IV), leucovorin (200 mg/m\^2 IV), oxaliplatin (85 mg/m\^2 IV), and docetaxel (50 mg/m\^2 IV) chemotherapy (FLOT) were to be administered before surgery starting on the day of the third dose of durvalumab. Subjects were to undergo surgery 6 to 8 weeks after completing chemotherapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions), FLOT or durvalumab plus FLOT at the discretion of the Investigator once recovered from surgery, provided that this was within 3 months of surgery.
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(radio)therapy
EXPERIMENTALDurvalumab (750 mg IV Q2W) was to be given for 2 doses. This was followed by five weekly doses of neoadjuvant paclitaxel (50 mg/m\^2 IV) / carboplatin (AUC 2) IV chemotherapy + radiotherapy (41.4 Gy radiotherapy given over 23 fractions) before surgery. Subjects could receive an additional dose of durvalumab after completion of chemoradiation. In Cohort D2, subjects continued durvalumab for 3 additional doses while receiving chemoradiation. Subjects were to undergo surgery 6 to 8 weeks after completing chemo(radio)therapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions) once recovered from surgery, provided that this was within 3 months of surgery.
Interventions
Anti PD-L1 antibody
Anti CTLA-4 antibody
IV administered chemotherapy
orally-administered chemotherapy
IV administered chemotherapy
IV administered Chemotherapy
IV administered chemotherapy
chemo-protective agent
IV administered chemotherapy
Eligibility Criteria
You may qualify if:
- 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
- Anticipated lifespan greater than 4 months.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- 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
- 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.
- Written informed consent obtained from the subject; subject been informed of other treatment options, and able to comply with study requirements.
- Age 18 years or older.
You may not qualify if:
- 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.
- Participation in another clinical study with an investigational product during the last 4 weeks.
- Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction.
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
- History of allogeneic organ transplant.
- 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.
- Known history of previous clinical diagnosis of tuberculosis.
- History of pneumonitis or interstitial lung disease.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Ludwig Institute for Cancer Researchlead
- AstraZenecacollaborator
Study Sites (4)
Research Facility
Dundee, DD1 9SY, United Kingdom
Research Facility
Nottingham, NG5 1PB, United Kingdom
Research Facility
Oxford, OX3 9DU, United Kingdom
Research Facility
Southampton, SO16 6YD, United Kingdom
Related Publications (1)
Bohnsack O, Hoos A, Ludajic K. Adaptation of the immune related response criteria: irRECIST. Ann Oncol. 2014 Sep;25(suppl 4):iv361-iv72 [Abstract 4958]. doi: 10.1093/annonc/mdu342.23.
BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Jonathan Skipper
- Organization
- Ludwig Institute for Cancer Research
Study Officials
- STUDY CHAIR
Mark Middleton
University of Oxford, UK
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 17, 2016
First Posted
April 12, 2016
Study Start
June 24, 2016
Primary Completion
June 16, 2022
Study Completion
June 16, 2022
Last Updated
March 22, 2024
Results First Posted
March 22, 2024
Record last verified: 2023-09
Data Sharing
- IPD Sharing
- Will not share