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

Ali Shamseddine

Status and phase: Active, not recruiting; Phase 2

Conditions: Locally Advanced Rectal Cancer

Treatments: Procedure: Total Mesorectal Excision; Drug: COMPOUND 2055269; Drug: mFOLFOX; Radiation: Radiation Therapy

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03503630

MS100070_0021 ISS (Other Grant/Funding Number)

BIO-2017-0422

Details and patient eligibility

About

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.

Full 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.

Enrollment: 44 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

44 participants in 1 patient group

Locally advanced rectal cancer patients

Experimental group

Description:

Week 1: D1-5: radiotherapy 25 Gy in 5 fractions 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) Week 16 or 17 (2 to 3 weeks after last cycle of chemotherapy + COMPOUND 2055269): Total Mesorectal Excision

Treatment:

Radiation: Radiation Therapy

Drug: mFOLFOX

Drug: COMPOUND 2055269

Procedure: Total Mesorectal Excision