Rectal Cancer
Conditions
Brief summary
This is a prospective, multicenter, open-label, single-arm Phase II study designed to evaluate the efficacy and safety of total neoadjuvant mFOLFOX6 combined with suvemcitug and enlonstobart in patients with MRI（Magnetic Resonance Imaging）-defined high-risk, mid-rectal, locally advanced rectal adenocarcinoma with pMMR/MSS status. All enrolled participants will receive 6 cycles of mFOLFOX6 plus suvemcitug and enlonstobart every 2 weeks. After 6 cycles, participants will undergo reassessment with pelvic MRI and systemic imaging. Participants who achieve at least 20% tumor regression on MRI without new high-risk radiologic features will continue with 2 additional cycles of mFOLFOX6 followed by radical total mesorectal excision surgery, without routine pelvic radiotherapy. Participants who do not meet the predefined regression threshold or show disease progression will receive long-course chemoradiotherapy with concurrent capecitabine, followed by 3 cycles of mFOLFOX6 and radical surgery.
Interventions
DRUGmFOLFOX6
Oxaliplatin 85 mg/m2 IV over 2 hours on Day 1; leucovorin calcium 400 mg/m2 IV over 2 hours on Day 1; 5-fluorouracil 400 mg/m2 IV bolus on Day 1; 5-fluorouracil 2400 mg/m2 continuous IV infusion over 46-48 hours;every 2 weeks, for 6 cycles during the initial total neoadjuvant treatment phase. Participants meeting the predefined MRI regression criterion will receive 2 additional cycles of mFOLFOX6 before surgery. Participants requiring chemoradiotherapy will receive 3 additional cycles of mFOLFOX6 after long-course chemoradiotherapy before surgery.
DRUGSuvemcitug
Suvemcitug 2 mg/kg IV infusion on Day 1 of each 14-day cycle, every 2 weeks, for 6 doses during the initial total neoadjuvant treatment phase.
DRUGEnlonstobart
Enlonstobart 240 mg IV infusion on Day 1 of each 14-day cycle, every 2 weeks, for 6 doses during the initial total neoadjuvant treatment phase.
RADIATIONPelvic Chemoradiotherapy
Used selectively for participants who do not achieve the predefined interim MRI regression threshold or who show disease progression. 45-50.4 Gy in 25-28 fractions. Oral capecitabine during radiotherapy.
PROCEDURETotal Mesorectal Excision
For participants omitting radiotherapy: approximately 2-4 weeks after completion of total neoadjuvant systemic therapy. For participants receiving chemoradiotherapy: after long-course chemoradiotherapy and subsequent mFOLFOX6 treatment, according to investigator assessment.
Sponsors
Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 to 75 years, male or female. 2. Histologically confirmed rectal adenocarcinoma. 3. pMMR or MSS status confirmed by genetic testing or immunohistochemistry. 4. Tumor lower margin located 5-12 cm from the anal verge, based on colonoscopy or MRI, consistent with mid-rectal cancer. 5. Pelvic MRI showing high-risk locally advanced rectal cancer, meeting at least one of the following criteria: cT3c/d, defined as tumor extension \>5 mm beyond the muscularis propria; cN2 disease, defined as \>=4 regional metastatic lymph nodes; definite extramural venous invasion positivity. 6. No distant metastasis confirmed by chest and abdominal imaging, including contrast-enhanced CT or MRI. 7. ECOG performance status of 0 or 1. 8. Adequate organ function, including absolute neutrophil count \>=1.5 x 10\^9/L; platelet count \>=100 x 10\^9/L; hemoglobin \>=9 g/dL; ALT and AST \<=2.5 x upper limit of normal; total bilirubin \<=1.5 x upper limit of normal; serum creatinine \<=1.5 x upper limit of normal or creatinine clearance \>=50 mL/min. 9. Not pregnant or breastfeeding. Participants of reproductive potential must agree to use effective contraception during study treatment and for the protocol-specified period after the last dose. 10. Voluntary participation with signed written informed consent.
Exclusion criteria
1. Imaging evidence of cT4 disease, mesorectal fascia positivity, or lateral lymph node metastasis. 2. Prior pelvic radiotherapy or prior systemic antitumor treatment for the current disease, including chemotherapy, targeted therapy, or immunotherapy. 3. Special histologic subtypes, including mucinous adenocarcinoma, signet-ring cell carcinoma, undifferentiated carcinoma, or other special histologic types. 4. Known allergy or contraindication to any component of the study drugs, including oxaliplatin, 5-fluorouracil, suvemcitug, or enlonstobart. 5. Active or previous severe autoimmune disease, including systemic lupus erythematosus or inflammatory bowel disease, or long-term use of systemic immunosuppressive agents. 6. Serious cardiovascular events within 6 months, including acute myocardial infarction or stroke, refractory hypertension, or NYHA class III-IV heart failure. 7. Active infection, including active tuberculosis, uncontrolled hepatitis B or C, or HIV infection with high viral load. 8. Other malignancy within 5 years, except cured localized skin cancer or carcinoma in situ. 9. Pregnancy or breastfeeding. 10. Inability to undergo MRI examination. 11. Multiple primary colorectal cancers. 12. Intestinal obstruction, intestinal perforation, or high risk of obstruction or perforation. 13. Hypertension that cannot be controlled to the normal range with antihypertensive therapy, defined as systolic blood pressure \>150 mmHg or diastolic blood pressure \>90 mmHg. 14. NYHA class III-IV cardiac insufficiency or left ventricular ejection fraction \<50% on echocardiography. 15. Proteinuria, defined as urine protein \>1+ at screening, or urine protein 1+ that does not return to normal on repeat testing within 24 hours. 16. Definite tendency for gastrointestinal bleeding, including active local ulcerative lesions with fecal occult blood positivity of ++; history of melena or hematemesis within 2 months; high risk of bleeding such as grade \>=3 bleeding within 6 months, hemoptysis \>=2.5 mL per episode, imaging evidence of tumor invasion into major blood vessels, or bleeding risk deemed unacceptable by the investigator. 17. High risk of gastrointestinal perforation or fistula, including gastrointestinal perforation or active peptic ulcer within 6 months, or pelvic tumor invasion of the bladder or rectum with potential fistula risk as judged by the investigator. 18. Coagulation abnormality, including INR \>1.5 or APTT \>1.5 x upper limit of normal, with bleeding tendency. 19. Chronic unhealed wound or fracture; major surgery within 4 weeks; or severe traumatic injury, fracture, or ulcer within 4 weeks. 20. Any condition that, in the investigator's judgment, makes the participant unsuitable for enrollment or unlikely to comply with follow-up.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathologic Complete Response Rate | Perioperative : at the time of surgery for pCR（Pathologic Complete Response Rate）. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| R0 Resection Rate | Perioperative : at the time of surgery. | — |
| Circumferential Resection Margin Negative Rate | Perioperative : at the time of surgery. | — |
| Major Pathologic Response Rate | Perioperative : at the time of surgery. | — |
| Proportion of Participants Receiving Pelvic Radiotherapy | At the end of Cycle 6 (each cycle is 14 days)" | — |
| Successful Radiotherapy Omission Rate | From enrollment to surgery. | — |
| Three-Year Disease-Free Survival | Up to 3 years after surgery | — |
| Quality of life will be evaluated using the European O-rganization for Reasearch and Treatment of Cancer Quality of Life Questionnaire-C30（EORTC QLQ-C30） (range 0-100). | Baseline, At the end of Cycle 6 (each cycle is 14 days),Perioperative | It evaluates the quality of life from 30 aspects, including appetite, mental status, sleep quality, fatigue, etc. The higher scores mean a better quality of life. |
Countries
China
Contacts
CONTACTWentao Tang
CONTACTTang
Outcome results
None listed