Neoadjuvant Short-course Radiotherapy Followed by the Combination of Immunotherapy and Chemotherapy in Locally Advanced Rectal Cancer

Locally Advanced Rectal Cancer Clinical Trial

Official title:

The Combination of Neoadjuvant Short-course Radiotherapy and Immunotherapy in Locally Advanced Rectal Cancer：A Open-label Single-arm Phase II Trial.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04663763
• Other study ID #: IRB-2020-336
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 1, 2020
• Est. completion date: December 1, 2025

Study information

• Verified date: December 2020
• Source: Zhejiang Cancer Hospital
• Contact: Yuping Zhu, MD
• Phone: 86-0571-88128011
• Email: drzyp[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: December 1, 2025
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Locally Advanced Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• PD-1 antibody
Sintilimab is a humanized IgG4 monoclonal antibody against the programmed death-1 (PD-1) receptor. Usage: 200mg ivgtt d1 q3w.
• Capecitabine
Usage: 1000mg/m2 d1-14 q3w
• Oxaliplatin
Usage: 130mg/m2 d1 q3w

Locations

Country	Name	City	State
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang Cancer Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	pCR rate	Pathologic complete response rate	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	3-year DFS	3-year disease free survival rate	Assessed up to 3 years
Secondary	3-year local recurrence rate	3-year local recurrence rate	Assessed up to 3 years
Secondary	3-year OS	3-year overall survival rate	Assessed up to 3 years
Secondary	Grade 3-4 adverse effects rate	Radiotherapy, immunotherapy and chemotherapy related grade 3-4 adverse events rate	Assessed up to 3 years
Secondary	Surgical complications	Type and Rate of surgical complications	Assessed up to 3 years from the TME surgery
Secondary	Quality of Life Scale	The Quality of Life Scale (QoLS, range 0-60) will be used to evaluate the quality of life. Higher scores mean the better quality of life	Assessed up to 5 years