Clinical trial NCT04663763: Neoadjuvant Short-course Radiotherapy Followed by the Combination of Immunotherapy and Chemotherapy in Locally Advanced Rectal Cancer
Official title: The Combination of Neoadjuvant Short-course Radiotherapy and Immunotherapy in Locally Advanced Rectal Cancer：A Open-label Single-arm Phase II Trial.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Rectal Cancer
Keywords: Neoadjuvant short-course radiotherapy
Immunotherapy
Locally advanced rectal cancer
Pathological complete response
Lead sponsor: Zhejiang Cancer Hospital
Sponsor class: OTHER
First posted: 2020-12-11
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single arm, open-label, prospective phase II clinical trial to evaluate the combination of neoadjuvant short-course radiotherapy and immunotherapy (PD-1 antibody) for patients with locally advanced rectal cancer (LARC). A total of 40 patients will be enrolled in this trial to receive 5\*5Gy short-course radiotherapy, followed by 4 cycles of CAPOX chemotherapy and PD-1 antibody. Then they will receive the TME surgery and another 4 cycles of CAPOX chemotherapy. There are two cohorts according to the microsatellite instability status: (1) the micro-satellite stable (MSS) cohort（n=32), (2) the MSI-high cohort (n=8). The primary end point is the rate of pathological complete response (pCR). The long-term prognosis and adverse effects will also be evaluated and analyzed.


Eligibility criteria: Inclusion Criteria:

* 1. Pathological confirmed rectal adenocarcinoma and the distance from anal verge less than 12 cm;

  2. Clinical stage T3-4 and/or N+ (AJCC 8th);

  3. No distant metastases;

  4. Age 18-70 years old, female and male;

  5. ECOG 0-1;

  6. No previous chemotherapy, radiotherapy, immunotherapy or other anti-tumor treatment;

  7. Adequate organ function defined at baseline as:
  1. ANC ≥1.5×109 /L，PLt ≥75×109 /L，Hb ≥90 g/L;
  2. TBIL ≤1.5×ULN, ALT ≤2.5ULN, AST ≤2.5ULN, BUN and Cr ≤1×ULN or Ccr ≥50ml/min (Cockcroft-Gault formula);
  3. INR ≤1.5×ULN or PT ≤1.5×ULN (If the patient is receiving anticoagulant therapy, PT should be within the intended use range of the anticoagulant drug);

  8. With good compliance and no serious comorbidity;

  9. Women of childbearing age must have taken reliable contraceptive measures or have a pregnancy test (serum or urine) within 7 days prior to enrollment and the results are negative;

  10. Subject volunteers to join the study, sign the informed consent.

Exclusion Criteria:

* 1. History of other uncured malignancies within 5 years. Cured tumor with good prognosis, such as skin basal cell carcinoma, cervical cancer and superficial bladder cancer, will be excluded;

  2. Have received surgery within 4 weeks before the enrollment;

  3. History of obstruction within 6 months before the enrollment;

  4. History of active autoimmune disease, interstitial lung disease, epilepsy and dysphrenia;

  5. With uncontrolled cardiovascular disease: active coronary heart disease; grade III-IV cardiac insufficiency according to the NYHA criteria; and myocardial infarction within 1 year;

  6. With active infection or fever of \>38.5 ℃ with unknown cause (tumor-induced fever judged could be enrolled);

  7. DPD deficiency;

  8. Allergic to any component of chemotherapy or immunotherapy;

  9. With congenital or acquired immunodeficiency (such as those with HIV infection), active hepatitis B or hepatitis C;

  10. Usage of corticosteroids (prednison dose of \> 10 mg/day) or other immunosuppressors for systemic treatment within the first 14 days of research;

  11. Receive attenuated live vaccine within 4 weeks before the research;

  12. Pregnant women or breast-feeding women;

  13. With other factors that would force to terminate the clinical trial ahead of time, such as the development of other severe comorbidity that required combined treatment, and family or social factors affecting the safety of patients or experimental data collection, as judged by the researchers.

Primary outcomes:
measure: pCR rate
timeFrame: The TME surgery will be recommended at 1 week after the neoadjuvant therapy. The pCR rate is evaluated after surgery. Assessed up to 6 months
Secondary outcomes:
measure: 3-year DFS
timeFrame: Assessed up to 3 years
measure: 3-year local recurrence rate
timeFrame: Assessed up to 3 years
measure: 3-year OS
timeFrame: Assessed up to 3 years
measure: Grade 3-4 adverse effects rate
timeFrame: Assessed up to 3 years
measure: Surgical complications
timeFrame: Assessed up to 3 years from the TME surgery
measure: Quality of Life Scale
timeFrame: Assessed up to 5 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Zhejiang Cancer Hospital
name: Yuping Zhu, MD
role: PRINCIPAL_INVESTIGATOR
References: