Short-course Radiation Followed by mFOLFOX-6 Plus COMPOUND 2055269 for Locally-advanced Rectal Adenocarcinoma

NCT03503630 | Unknown Phase 2 DMC

• 2 other identifiers: BIO-2017-0422MS100070_0021 ISS
• Study Type: interventional
• Target: 44
• Locations: 2 countries
• Sites: 3

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.

Conditions

Locally Advanced Rectal Cancer

Keywords

Locally advanced rectal cancer; Immunotherapy; Short course radiation; Folfox; Response rate

Outcome Measures

Primary Outcomes (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

  Will be done via pathologic assessment on the surgical specimen

  After 17 weeks (once surgery is done)

Secondary Outcomes (4)

• The proportion of patients who remain progression free at 3 years.

  3 years

• PD-L1 expression and T-cell infiltration changes after treatment

  At day 10 biopsy and after 17 weeks (once surgery is done)

• Number of participants with treatment- related adverse events as assessed by NCI-CTCAE v4.0

  3 years

• Quality of life of the patients in a neoadjuvant setting with COMPOUND 2055269 as assessed by FACT-C questionnaire

  3 years

Study Arms (1)

Locally advanced rectal cancer patients

EXPERIMENTAL

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; Radiation: Radiation Therapy; Drug: mFOLFOX; Procedure: Total Mesorectal Excision

Interventions

COMPOUND 2055269 DRUG

COMPOUND 2055269 to be given every 2 weeks with chemotherapy for 6 cycles

Locally advanced rectal cancer patients

Radiation Therapy RADIATION

Radiotherapy 25 Gy to be given on Days 1-5

Locally advanced rectal cancer patients

mFOLFOX DRUG

Given every 2 weeks for 6 cycles

Locally advanced rectal cancer patients

Total Mesorectal Excision PROCEDURE

Surgery to be done 2-3 weeks after last cycle of chemotherapy and COMPOUND 2055269

Locally advanced rectal cancer patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged ≥18 years.
• Locally-advanced rectal cancer (cT2 N1-3, cT3 N0-3, evidence of extramural vascular or mesorectal fascia involvement).
• \<12 cm from anal verge.
• Histologically proven rectal adenocarcinoma.
• ECOG performance score ≤ 1.
• 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).
• Negative serum or urine pregnancy test at screening for women of childbearing potential.
• 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.

You may not qualify if:

• Distant metastasis (M1).
• Patients with T2 N0 or T4.
• Recurrent rectal cancer.
• Symptoms or history of peripheral neuropathy.
• Prior radiotherapy or chemotherapy.
• 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).
• 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.
• Vaccination within 4 weeks of the first dose of COMPOUND 2055269 and while on trials is prohibited except for administration of inactivated vaccines.
• Active infection requiring systemic therapy.
• Known history of testing positive for the human immunodeficiency virus or known acquired immunodeficiency syndrome.
• 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).
• 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).

Sponsors & Collaborators

• Ali Shamseddine: lead
• Merck KGaA, Darmstadt, Germany: collaborator
• Phoenix Clinical Research: collaborator

Study Sites (3)

King Hussein Cancer Center

Amman, Jordan

Location

American University of Beirut Medical Center

Beirut, Lebanon

Location

Hôtel Dieu de France

Beirut, Lebanon

Location

Related Publications (2)

• Shamseddine A, Zeidan YH, El Husseini Z, Kreidieh M, Al Darazi M, Turfa R, Kattan J, Khalifeh I, Mukherji D, Temraz S, Alqasem K, Amarin R, Al Awabdeh T, Deeba S, Jamali F, Mohamad I, Elkhaldi M, Daoud F, Al Masri M, Dabous A, Hushki A, Jaber O, Charafeddine M, Geara F. Efficacy and safety-in analysis of short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced rectal adenocarcinoma. Radiat Oncol. 2020 Oct 7;15(1):233. doi: 10.1186/s13014-020-01673-6.

  PMID: 33028346 DERIVED

• Shamseddine A, Zeidan YH, Kreidieh M, Khalifeh I, Turfa R, Kattan J, Mukherji D, Temraz S, Alqasem K, Amarin R, Al Awabdeh T, Deeba S, Jamali F, Mohamad I, Elkhaldi M, Daoud F, Al Masri M, Dabous A, Hushki A, Jaber O, Khoury C, El Husseini Z, Charafeddine M, Al Darazi M, Geara F. Short-course radiation followed by mFOLFOX-6 plus avelumab for locally-advanced rectal adenocarcinoma. BMC Cancer. 2020 Sep 1;20(1):831. doi: 10.1186/s12885-020-07333-y.

  PMID: 32873251 DERIVED

MeSH Terms

Interventions

Radiotherapy

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Ali I Shamseddine, M.D.

  American University of Beirut Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 29, 2018
• First Posted: April 20, 2018
• Study Start: July 20, 2018
• Primary Completion: March 15, 2021
• Study Completion: July 2, 2024
• Last Updated: January 31, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

JO (1); LE (2)