An Open-Label Multicenter Phase 1b Study of E7046 in Combination With Radiotherapy/Chemoradiotherapy (RT/CRT) in Preoperative Treatment of Subjects With Rectum Cancer

Status: Completed
Location: See all (5) locations...
Intervention Type: Radiation, Drug
Study Type: Interventional
Study Phase: Phase 1
SUMMARY

This is a multicenter, open-label, Phase 1b study in participants with locally advanced rectum cancer where primary resection without chemoradiotherapy is unlikely to achieve clear margins as defined by magnetic resonance imaging (MRI). It is conducted to assess the safety, to assess the tolerability, and to determine the recommended Phase 2 dose (RP2D) of E7046 in combination with pre-operative chemoradiotherapy. The study will also assess the efficacy of the combination in the expansion part at RP2D.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Diagnosis of histologically confirmed invasive primary rectal carcinoma

• Age ≥18 years at the time of informed consent

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

• Participants must have locally advanced rectum cancer where primary resection without chemoradiotherapy (CRT) is unlikely to achieve clear margins as defined by magnetic resonance imaging (MRI), with no metastatic disease, as assessed by independent review.

• Disease that can be encompassed within a radical radiotherapy treatment volume

• Participant must consent to repeated biopsy to allow the acquisition of fresh and/or formalin-fixed paraffin-embedded (FFPE) material. Available archived tumor material may be submitted as the pretreatment biopsy provided that minimum requirements are met by local pathology review as defined in the laboratory manual. If archived tumor material is not available or does not meet minimum requirements, then a fresh tumor biopsy must be obtained in accordance with local institutional practice.

• Adequate renal function defined as serum creatinine \<1.5 × upper limit of normal (ULN) (or use System of Units \[SI\] units or calculated creatinine clearance ≥50 milliliter per minute \[mL/min\] per the Cockcroft and Gault formula)

• Adequate bone marrow function:

‣ Absolute neutrophil count (ANC) ≥1500/millimeters cubed (mm\^3) (≥1.5 × 10\^3/microliters \[µL\])

⁃ Platelets ≥100,000/mm\^3 (≥100 × 10\^9/Liters \[L\])

⁃ Hemoglobin ≥9.0 grams per deciliter (g/dL)

• Adequate liver function:

‣ Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) ≤1.5

⁃ Total bilirubin ≤1.5 × ULN except for unconjugated hyperbilirubinemia or Gilbert's syndrome

⁃ Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤2.5 × ULN

• No prior pelvic radiotherapy, chemotherapy, immunotherapy, or other anti-cancer treatment for rectal cancer

• No prior exposure to colony stimulating factor 1 receptor (CSF1R) antagonists such as but not limited to emactuzumab (RG7155) (Roche), PLX3397 (Plexicon), JNJ40346627 (Johnson \& Johnson), including both anti-CSF1R and small molecule inhibitors and prostaglandin E2 receptor 4 (EP4) antagonists

• No preexisting condition that would deter radiotherapy, eg, fistulas, severe ulcerative colitis (particularly participants currently taking sulphasalazine), Crohn's disease, prior adhesions

• Willing and able to give informed consent and comply with all aspects of the protocol

Locations
United States
Massachusetts
Massachusetts General Hospital
Boston
New York
Weill Cornell
New York
Other Locations
Poland
Marie-Skodowska Curie Cancer Centre
Warsaw
United Kingdom
The Christie
Manchester
Mount Vernon Hospital
Northwood
Time Frame
Start Date: 2017-05-17
Completion Date: 2021-09-30
Participants
Target number of participants: 29
Treatments
Experimental: E7046 in combination with Long Course Chemoradiotherapy (LCRT)
Participants will receive once daily (QD) doses of E7046 (recommended Phase 2 dose \[RP2D\] determined in the Dose-Escalation part of the study) for 10 weeks, starting on Day 1, 14 days prior to initiation of the radiotherapy. LCRT will be initiated on Day 15 and will consist of a total of 45 Grays (GY) radiation administered in 1.8 GY daily doses delivered for 5 days (Monday to Friday) every week for 5 weeks. Capecitabine (825 milligrams per meters squared \[mg/m\^2\]) will be administered twice daily on the days of radiotherapy. Surgery will be performed 14 to 16 weeks from the first day of E7046 treatment.
Experimental: E7046 in combination with SCRT followed by chemotherapy
Participants will receive QD doses of E7046 (RP2D determined in the Dose-Escalation part of the study) for 10 weeks, starting on Day 1, 14 days prior to initiation of the radiotherapy. Short course radiotherapy (SCRT) will be initiated on Day 15 and will consist of a total of 25 Gy radiation administered in 5 Gy daily doses for 5 days (Monday to Friday) for 1 week. Ten days after the end of radiotherapy, 3 cycles of the modified folinic acid/5-FU/oxaliplatin (mFOLFOX-6) regimen will be administered every 2 weeks for 2 consecutive days. Surgery will be performed 14 to 16 weeks from the first day of E7046 treatment.
Related Therapeutic Areas
Sponsors
Leads: Adlai Nortye Biopharma Co., Ltd.

This content was sourced from clinicaltrials.gov

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