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Trial record 1 of 1 for:    mfolfox | Lebanon
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Short-course Radiation Followed by mFOLFOX-6 Plus COMPOUND 2055269 for Locally-advanced Rectal Adenocarcinoma

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ClinicalTrials.gov Identifier: NCT03503630
Recruitment Status : Active, not recruiting
First Posted : April 20, 2018
Last Update Posted : March 22, 2019
Sponsor:
Collaborators:
Merck KGaA, Darmstadt, Germany
Phoenix Clinical Research
Information provided by (Responsible Party):
Ali Shamseddine, American University of Beirut Medical Center

Brief Summary:
The purpose of this study is to show that the addition of COMPOUND 2055269, an immunotherapeutic drug, to Folfox chemotherapy will improve the pathologic complete response rate in patients with locally advanced rectal cancer.

Condition or disease Intervention/treatment Phase
Locally Advanced Rectal Cancer Drug: COMPOUND 2055269 Radiation: Radiation Therapy Drug: mFOLFOX Procedure: Total Mesorectal Excision Phase 2

Detailed Description:

The purpose of this study is to show that the addition of COMPOUND 2055269, an immunotherapeutic drug, to Folfox chemotherapy will improve the pathologic complete response rate in patients with locally advanced rectal cancer.

COMPOUND 2055269 has demonstrated meaningful clinical activity across various tumor types and treatment settings. No clinical trial is conducted over COMPOUND 2055269 in locally-advanced rectal adenocarcinoma.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Short-course Radiation Followed by mFOLFOX-6 Plus COMPOUND 2055269 for Locally-advanced Rectal Adenocarcinoma
Actual Study Start Date : July 20, 2018
Estimated Primary Completion Date : May 13, 2023
Estimated Study Completion Date : May 13, 2023

Arm Intervention/treatment
Experimental: Locally advanced rectal cancer patients
  1. Week 1: D1-5: radiotherapy 25 Gy in 5 fractions
  2. mFOLFOX-6: Oxaliplatin 85 mg/m2 in a 2-hour infusion Leucovorin 400 mg/m² over 2 hours Bolus fluorouracil 400 mg/m² followed by a 48-hour infusion of fluorouracil 2,400 mg/m² + COMPOUND 2055269 10 mg/kg every 2 weeks (first administration at D15, for a total of 6 cycles)
  3. Week 16 or 17 (2 to 3 weeks after last cycle of chemotherapy + COMPOUND 2055269): Total Mesorectal Excision
Drug: COMPOUND 2055269
COMPOUND 2055269 to be given every 2 weeks with chemotherapy for 6 cycles

Radiation: Radiation Therapy
Radiotherapy 25 Gy to be given on Days 1-5

Drug: mFOLFOX
Given every 2 weeks for 6 cycles

Procedure: Total Mesorectal Excision
Surgery to be done 2-3 weeks after last cycle of chemotherapy and COMPOUND 2055269




Primary Outcome Measures :
  1. The primary objective of the study is to evaluate the pathologic complete response (pCR) rate following short-course radiation then mFOLFOX-6/COMPOUND 2055269 [ Time Frame: After 17 weeks (once surgery is done) ]
    Will be done via pathologic assessment on the surgical specimen


Secondary Outcome Measures :
  1. The proportion of patients who remain progression free at 3 years. [ Time Frame: 3 years ]
    1) Progression free survival is measured by imaging and serial tumor markers during follow up visits

  2. PD-L1 expression and T-cell infiltration changes after treatment [ Time Frame: At day 10 biopsy and after 17 weeks (once surgery is done) ]
    2) PD-L1 & T cell infiltration is measured by a pathology assessment on day 10 and after surgery

  3. Number of participants with treatment- related adverse events as assessed by NCI-CTCAE v4.0 [ Time Frame: 3 years ]
    Treatment- related adverse events are assessed by NCI-CTCAE v4.0 in each visit

  4. Quality of life of the patients in a neoadjuvant setting with COMPOUND 2055269 as assessed by FACT-C questionnaire [ Time Frame: 3 years ]
    Quality of life is measured via FACT-C questionnaire in each visit.



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. Patients aged ≥18 years.
  2. Locally-advanced rectal cancer (cT2 N1-3, cT3 N0-3, evidence of extramural vascular or mesorectal fascia involvement).
  3. <12 cm from anal verge.
  4. Histologically proven rectal adenocarcinoma.
  5. ECOG performance score ≤ 1.
  6. 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).
  7. Negative serum or urine pregnancy test at screening for women of childbearing potential.
  8. Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after last COMPOUND 2055269 treatment administration if the risk of conception exists.

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., intraarticular 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. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
  8. Vaccination within 4 weeks of the first dose of COMPOUND 2055269 and while on trials is prohibited except for administration of inactivated vaccines.
  9. Active infection requiring systemic therapy.
  10. Known history of testing positive for the human immunodeficiency virus or known acquired immunodeficiency syndrome.
  11. 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).
  12. 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).
  13. 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.
  14. 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.
  15. Prior organ transplantation including allogenic stem-cell transplantation.
  16. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  17. Concurrent treatment with a non-permitted drug.
  18. Patients suspected by the physician that he/she will not compliant to the protocol conduct.
  19. Pregnant or breastfeeding patients.
  20. Patient participating in another clinical trial.
  21. Patient who is not willing to sign the consent form.
  22. Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
  23. Legal incapacity or limited legal capacity patients receiving other oncology specific medication not authorized in the protocol.

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): NCT03503630


Locations
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Jordan
King Hussein Cancer Center
Amman, Jordan
Lebanon
American University of Beirut Medical Center
Beirut, Lebanon
Hôtel Dieu de France
Beirut, Lebanon
Sponsors and Collaborators
Ali Shamseddine
Merck KGaA, Darmstadt, Germany
Phoenix Clinical Research
Investigators
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Principal Investigator: Ali I Shamseddine, M.D. American University of Beirut Medical Center

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Responsible Party: Ali Shamseddine, Principal Investigator, American University of Beirut Medical Center
ClinicalTrials.gov Identifier: NCT03503630     History of Changes
Other Study ID Numbers: BIO-2017-0422
MS100070_0021 ISS ( Other Grant/Funding Number: Merck KGaA, Darmstadt, Germany )
First Posted: April 20, 2018    Key Record Dates
Last Update Posted: March 22, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Ali Shamseddine, American University of Beirut Medical Center:
Locally advanced rectal cancer
Immunotherapy
Short course radiation
Folfox
Response rate

Additional relevant MeSH terms:
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Adenocarcinoma
Rectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases