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Trial details
Short-Course Radiation Followed by mFOLFOX-6 Plus COMPOUND 2055269 for Locally-Advanced Rectal Adenocarcinoma
Current status:
Approved
|
Date registered:
29/12/2018
|
Date last updated:
28/12/2018
Trial version(s)
Current: 28/11/2018
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Main Information
Primary registry identifying number
LBCTR2018120174
Protocol number
BIO-2017-0422
MOH registration number
20796/2018
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Retrospective
Type of registration: Justify
This is because the trial was initiated prior to the activation of this registry
Date of registration in national regulatory agency
16/05/2018
Primary sponsor
American University of Beirut
Primary sponsor: Country of origin
Lebanon
Public title
Short-Course Radiation Followed by mFOLFOX-6 Plus COMPOUND 2055269 for Locally-Advanced Rectal Adenocarcinoma
Acronym
NA
Scientific title
Short-Course Radiation Followed by mFOLFOX-6 Plus COMPOUND 2055269 for Locally-advanced Rectal Adenocarcinoma
Acronym
NA
Brief summary of the study: English
The purpose of this research trial is to investigate a new drug, COMPOUND 2055269, in the treatment of locally advanced rectal adenocarcinoma. COMPOUND 2055269 is a fully human antibody directed against programmed death ligand-1 (PD-L1) blocking antibody that results in the restoration of anti-tumor immune responses. COMPOUND 2055269 is already available in the market for treatment of bladder cancer and Merkel-Cell carcinoma, an aggressive type of skin cancer. COMPOUND 2055269is still being tested for safety and effectiveness in different types of cancer, including rectal cancer. The standard treatment for participants' condition involves radiation to the rectum followed by chemotherapy then surgery. In this clinical trial, we will be adding COMPOUND 2055269 to the chemotherapy treatment for 6 doses for all patients before surgery.
Brief summary of the study: Arabic
تهدف هذه الدراسة البحثية إلى التحقق من مفعول دواء جديد، COMPOUND 2055269، في علاج سرطان المستقيم المتقدم محلياً. الأفيلوماب مضادّ مناعيّ بشريّ يستهدف خلايا الموت المبرمج-1 (بي دي أل 1) فيعمل على تعطيل آلية تستخدمها الأورام للاختباء من جهاز المناعة. لعلاج سرطان المثانة وسرطان خليّة مركل، وهو نوع شرس من أنواع سرطانات الجلد. ولا تزال الاختبارات جارية على هذا الدواء للتحقق من مدى سلامته وفعاليته في علاج أنواع مختلفة من السرطان، بما في ذلك سرطان المستقيم. يتمثل العلاج النموذجي المناسب لحالتك الصحية بالخضوع لعلاج إشعاعي للمستقيم، يتبعه علاج كيميائي، وتأتي الجراحة في المرحلة النهائية. في هذه التجربة السريرية، سنقوم بإضافة الأفيلوماب على العلاج الكيميائي ل6 جرعات لجميع المرضى قبل خضوعهم للجراحة.
Health conditions/problem studied: Specify
Locally-Advanced Rectal Adenocarcinoma
Interventions: Specify
Visit 1 1. Informed consent 2. Baseline laboratory tests including free T4, TSH, Hepatitis B virus surface antigen, and Hepatitis C virus antibodies 3. Tissue blocks or at least 7 slides of the baseline biopsy specimen upon which diagnosis was based 4. PD-L1 expression on tumor cells and TILs will be assessed by the pathologist at AUBMC. Also, CD4+, CD8+ and CD3+ T cell infiltration will be quantified in mm2 in the most abundant tumor-infiltrating area in both, the stroma and the tumor, of the baseline biopsy. Microsatellite instability, MSI or MMR status, will be evaluated once on either the baseline biopsy or day 10 (D10) biopsy, and the predictive markers to be assessed are: MLH-1, MSH-2, MSH-6, and PMS-2. VISITS 2-6 (Week 1 ± 3 days; Day 1-5) 1. SCRT will be administered for 5 days from day 1 (D1) to D5 during week 1 (Either 3D conformal or in intensity-modulated radiotherapy (IMRT) treatment planning may be used. The daily dose will be 5 Gy to a total dose of 25 Gy.) VISIT 7 (Week 2 ± 3 days; Day 10) 2. Sigmoidoscopy will be performed and a biopsy taken 3. Slides of the corresponding specimen will be provided 4. PD-L1 expression on tumor cells and TILs will be assessed by the pathologist at AUBMC. Also, CD4+, CD8+ and CD3+ T cell infiltration will be quantified in mm2 in the most abundant tumor-infiltrating area in both, the stroma and the tumor, of the baseline biopsy. Microsatellite instability, MSI or MMR status, will be evaluated once on either the baseline biopsy or day 10 (D10) biopsy, and the predictive markers to be assessed are: MLH-1, MSH-2, MSH-6, and PMS-2. VISITS 8-13 (Week 3 ± 3 days to week 13 ± 3 days; Day 15+) 1. mFOLFOX-6 chemotherapy plus avelumab will be administered every 2 weeks for 6 cycles. 2. Avelumab at a dose of 10mg/kg is administered, followed 30 minutes later by mFOLFOX as follows: 85 mg/m2 of oxaliplatin in a 2-hour infusion, 400 mg/m2 of leucovorin over 2 hours, followed by a 48-hour infusion of fluorouracil 2,400 mg/m2. 3. Hematologic and biochemical laboratory tests are ordered prior to every cycle. D 4. Visit 13 is the end of treatment visit which includes, in addition to the procedures mentioned above, an assessment of tumor markers (CEA and CA 19-9). Visit 14 (Week 16 or 17 ± 3 days) 1. 2 to 3 weeks after last cycle of mFOLFOX-6 plus avelumab, an open, laparoscopic, or robotic TME is performed at the corresponding site. 2. An optional pelvic MRI might be ordered prior to surgery to evaluate the patient’s disease status. 3. All TME procedures will be video recorded and the corresponding videotapes and images of the resected specimens are to be provided to AUBMC. 4. All specimens are to be processed and graded using the recommendations of the College of American Pathologists 5. PD-L1 expression on tumor cells and TILs will be assessed. 6. CD4+, CD8+ and CD3+ T-cell infiltration will be quantified in mm2 in the most abundant tumor-infiltrating area in both, the stroma and the tumor, of the tumor excision specimen. Follow-up Visits 1. Follow-up laboratory tests including tumor markers (CEA, Ca19-9) are to be performed every 3 months for 3 years after the surgical procedure.
Key inclusion and exclusion criteria: Inclusion criteria
Inclusion Criteria 1) Signed informed consent form. 2) Patients aged ≥18 years. 3) Locally-advanced rectal cancer cT2 N1-3, cT3 N0-3 4) < 12 cm from anal verge. 5) Histologically proven rectal adenocarcinoma. 6) ECOG performance score ≤ 1. 7) Have adequate organ function by meeting the following: • Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; • Platelet count ≥ 100 × 109/L; • Hemoglobin ≥ 9 g/dL; • Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range; • AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver); • Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method). 8) Negative serum or urine pregnancy test at screening for women of childbearing potential.
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
100
Key inclusion and exclusion criteria: Exclusion criteria
Exclusion Criteria 1) Distant metastasis (M1). 2) Patients with T2 N0 or T4. 3) Recurrent rectal cancer. 4) Symptoms or history of peripheral neuropathy. 5) Prior radiotherapy or chemotherapy. 6) Current use of immunosuppressive medication except for the following: - Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); - Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; - Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). 7) Concurrent treatment with a non-permitted drug. 8) Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. 9) Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines. 10) Active infection requiring systemic therapy. 11) Known history of testing positive for the human immunodeficiency virus or known acquired immunodeficiency syndrome. 12) Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive). 13) Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3). 14) Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication. 15) Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator’s judgment are acceptable. 16) Prior organ transplantation including allogenic stem-cell transplantation. 17) Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
N/A: Single arm study
Study design: Masking
N/A
Study design: Control
Uncontrolled
Study phase
2
Study design: Purpose
Treatment
Study design: Assignment
Single
IMP has market authorization
Yes, Lebanon and Worldwide
IMP has market authorization: Specify the countries
Lebanon and Worldwide
Name of IMP
Avelumab
Year of authorization
2017
Month of authorization
3
Type of IMP
Immunological
Pharmaceutical class
Immunotherapy: COMPOUND 2055269 is a fully human antibody directed against programmed death ligand-1 (PD-L1) blocking antibody that results in the restoration of anti-tumor immune responses.
Therapeutic indication
The standard treatment for locally advanced rectal adenocarcinoma involves radiation to the rectum followed by chemotherapy then surgery. In this clinical trial, we will be adding COMPOUND 2055269 to the chemotherapy treatment for 6 doses for all patients before surgery. Reasoning: COMPOUND 2055269 10 mg/kg once every 2 weeks has demonstrated meaningful clinical activity across various treatment settings and tumor types, including melanoma and lung cancer.
Therapeutic benefit
There is no guarantee that patients will receive any direct benefits from this study. Information from this study may help doctors learn more about COMPOUND 2055269 and the treatment of locally advanced rectal cancer. This information may benefit other patients with cancer of the rectal cancer. In this trial, we hope many participants will attain pathologic complete response (pCR) by the end of treatment.
Biospecimen retention
Samples with DNA**
Biospecimen description
1. Slides or Tissue Blocks prepared from the Baseline Biopsy from the rectal mass (taken during diagnostic colonoscopy) 2. Slides or Tissue Blocks prepared from the Biopsy taken from the rectal mass during sigmoidoscopy at Day 10 3. Slides or Tissue Blocks encompassing the entire tumor bed prepared from the gross specimen from the total mesorectal excision procedure.
Target sample size
44
Actual enrollment target size
Date of first enrollment: Type
Actual
Date of first enrollment: Date
20/07/2018
Date of study closure: Type
Actual
Date of study closure: Date
20/10/2023
Recruitment status
Recruiting
Date of completion
IPD sharing statement plan
No
IPD sharing statement description
Not Applicable
Additional data URL
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
Sources of Monetary or Material Support
Name
Secondary Sponsors
Name
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Ali
Shamseddine
Department of Internal Medicine Division of Hematology/Oncology American University of Beirut Medical Center Beirut P.O. Box 11-0236, Lebanon
Lebanon
Phone: +961 1 350 000 (Ext.: 5390)
Email: as04@aub.edu.lb
American University of Beirut Medical Center
Scientific
Ali
Shamseddine
Department of Internal Medicine Division of Hematology/Oncology American University of Beirut Medical Center Beirut P.O. Box 11-0236, Lebanon
Lebanon
Phone: +961 1 350 000 (Ext.: 5390)
Email: as04@aub.edu.lb
American University of Beirut Medical Center
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
American University of Beirut Medical Center
Ali Shamseddine, MD, FRCP
Oncologist
Approved
Hotel Dieu de France
Joseph Kattan, MD
Oncologist
Approved
King Hussein Cancer Center
Rim Turfa, MD
Oncologist
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
American University of Beirut Medical Center
04/06/2018
Fuad Ziyadeh (Chairperson of the IRB at AUBMC)
fz05@aub.edu.lb
Phone:01350000 Ext: 5353
Countries of Recruitment
Name
Lebanon
Jordan
Health Conditions or Problems Studied
Condition
Code
Keyword
Locally Advanced Rectal Cancer
Malignant neoplasm of rectum (C20)
Locally Advanced Rectal Cancer
Interventions
Intervention
Description
Keyword
Visit 1- Baseline laboratory tests including free T4, TSH, Hepatitis B virus surface antigen, and Hepatitis C virus antibodies
Visit 1
Visit 1
Visit 1- Tissue blocks or at least 7 slides of the baseline biopsy specimen upon which diagnosis was based
Visit 1
Visit 1
Visit 1- PD-L1 expression on tumor cells and Tumor infiltrating lymphocytes will be assessed by the pathologist at AUBMC. Also, CD4+, CD8+ and CD3+ T cell infiltration will be quantified in mm2 in the most abundant tumor-infiltrating area in both, the stroma and the tumor, of the baseline biopsy. Microsatellite instability, MSI or MMR status, will be evaluated once on either the baseline biopsy or day 10 (D10) biopsy, and the predictive markers to be assessed are: MLH-1, MSH-2, MSH-6, and PMS-2.
Visit 1
Visit 1
Visits 2-6 - Short Course Radiation Therapy will be administered for 5 days from day 1 (D1) to D5 during week 1 (Either 3D conformal or in intensity-modulated radiotherapy (IMRT) treatment planning may be used. The daily dose will be 5 Gy to a total dose of 25 Gy.)
Visits 2-6
Visits 2-6
Visit 7- Sigmoidoscopy will be performed and a biopsy taken
Visit 7
Visit 7
Visit 7- Slides of the corresponding specimen will be provided
Visit 7
Visit 7
Visit 7- PD-L1 expression on tumor cells and TILs will be assessed by the pathologist at AUBMC. Also, CD4+, CD8+ and CD3+ T cell infiltration will be quantified in mm2 in the most abundant tumor-infiltrating area in both, the stroma and the tumor, of the baseline biopsy. Microsatellite instability, MSI or MMR status, will be evaluated once on either the baseline biopsy or day 10 (D10) biopsy, and the predictive markers to be assessed are: MLH-1, MSH-2, MSH-6, and PMS-2.
Visit 7
Visit 7
Visits 8-13- mFOLFOX-6 chemotherapy plus COMPOUND 2055269 will be administered every 2 weeks for 6 cycles.
Visits 8-13
Visits 8-13
Visits 8-13- COMPOUND 2055269 at a dose of 10mg/kg is administered, followed 30 minutes later by mFOLFOX as follows: 85 mg/m2 of oxaliplatin in a 2-hour infusion, 400 mg/m2 of leucovorin over 2 hours, followed by a 48-hour infusion of fluorouracil 2,400 mg/m2.
Visits 8-13
Visits 8-13
Visits 8-13- Hematologic and biochemical laboratory tests are ordered prior to every cycle
Visits 8-13
Visits 8-13
Visit 13- This is the end of treatment visit which includes, in addition to the procedures mentioned above, an assessment of tumor markers (CEA and CA 19-9).
Visit 13
Visit 13
Visit 14- 2 to 3 weeks after last cycle of mFOLFOX-6 plus avelumab, an open, laparoscopic, or robotic TME is performed at the corresponding site. All TME procedures will be video recorded and the corresponding videotapes and images of the resected specimens are to be provided to AUBMC.
Visit 14
Visit 14
Visit 14- An optional pelvic MRI might be ordered prior to surgery to evaluate the patient’s disease status.
Visit 14
Visit 14
Visit 14- All specimens are to be processed and graded using the recommendations of the College of American Pathologists PD-L1 expression on tumor cells and TILs will be assessed. CD4+, CD8+ and CD3+ T-cell infiltration will be quantified in mm2 in the most abundant tumor-infiltrating area in both, the stroma and the tumor, of the tumor excision specimen.
Visit 14
Visit 14
Follow-up Visits- Follow-up laboratory tests including tumor markers (CEA, Ca19-9) are to be performed every 3 months for 3 years after the surgical procedure.
Follow-up Visits
Follow-up Visits
Primary Outcomes
Name
Time points
Measure
The primary efficacy endpoint is the proportion of patients who achieve a pathological complete response, defined as no viable tumor cells on the resected specimen.
The primary efficacy endpoint is the proportion of patients who achieve a pathological complete response, defined as no viable tumor cells on the resected specimen.
The primary efficacy endpoint is the proportion of patients who achieve a pathological complete response, defined as no viable tumor cells on the resected specimen.
Key Secondary Outcomes
Name
Time points
Measure
The secondary efficacy endpoints are: 1) PFS at 3 years will be estimated with the Kaplan-Meier method and presented with the 95% CI. 2) Evaluation of response by obtaining TRG just after surgery (week 16 or 17 ± 3 days).
The secondary efficacy endpoints are: 1) PFS at 3 years will be estimated with the Kaplan-Meier method and presented with the 95% CI. 2) Evaluation of response by obtaining TRG just after surgery (week 16 or 17 ± 3 days).
The secondary efficacy endpoints are: 1) PFS at 3 years will be estimated with the Kaplan-Meier method and presented with the 95% CI. 2) Evaluation of response by obtaining TRG just after surgery (week 16 or 17 ± 3 days).
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Download as PDF
Save a PDF copy of the summary of the trial