The Combination of Hypofractionated Radiotherapy and Immunotherapy in Locally Recurrent Rectal Cancer

NCT05628038 | Recruiting Phase 2

• 1 other identifier: FDRT-2022-289-3006
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a prospective, single-center, single-arm, two-cohort, phase II clinical trial. Patients aged 18 years or older who had pelvic recurrence rectal cancer with or without resectable distant metastasis, with treatment naive disease (cohort A) or progressive disease after first-line chemotherapy (cohort B), Eastern Cooperative Oncology Group performance status of 0-1, will receive 25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation (pelvic radiation history), 18 weeks toripalimab and investigator's choice of chemotherapy +/- target therapy, and stereotactic ablative radiotherapy (SABR) for all metastatic lesions between chemoimmunotherapy cycles, followed by multidisciplinary team (MDT) for decision:follow-up of complete response (CR), radical surgery, sustained treatment of non resection, or exit. The primary endpoint was local objective response rate. Secondary endpoints were extrapelvic objective response rate, R0 resection rate, duration of response, progression-free survival, overall survival, and safety and tolerability of the treatment. Shanghai Junshi Biomedical Technology Co., Ltd. Provides the first three cycles of toripalimab for free and has purchased liability insurance for clinical trial subjects.

Conditions

Recurrent Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Local objective response rate

  the proportion of patients with the best pelvic response of confirmed complete or partial response according to RECIST 1.1, as assessed by the investigator.

  up to 1 year

Secondary Outcomes (6)

• Extrapelvic objective response rate

  up to 1 year

• R0 resection rate

  up to 1 year

• Duration of response (DOR)

  up to 1 year

• Progression-Free Survival

  up to 3 year

• Overall Survival

  up to 3 year

Study Arms (1)

Treatment arm

EXPERIMENTAL

The enrolled patients will receive 25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation (pelvic radiation history) for pelvic recurrence. Cohort A patients will receive CAPOX, FOLFIRI or mFOLFOX6 chemotherapy andcohort B patients will receive CAPOX, FOLFIRI, mFOLFOX6, mXELIRI, irinotecan and raltitrexed, or oxaliplatin and raltitrexed chemotherapy, based on previous chemotherapy and adverse reactions to chemotherapy agents or at the discretion of the oncologist. All metastasis sites will receive stereotactic ablative radiotherapy (SABR) between chemoimmunotherapy cycles. Five-fraction regimens (25-50Gy/5Fx) are delivered daily. Dose Constraints are based on SABR-COMET 10 trial. Besides, according to the medical oncologist recommendation, patients with unresectable pelvic recurrence or distant metastasis will receive target therapy based on the KRAS/NRAS/BRAF mutation station.

Drug: PD-1 antibody; Drug: Capecitabine; Drug: 5FU; Drug: folinic acid; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Raltitrexed; Drug: Cetuximab; Drug: Bevacizumab; Radiation: Radiation

Interventions

PD-1 antibody DRUG

PD-1 antibody (Toripalimab): 240mg q3w or 160mg q2w

Also known as: Toripalimab

Treatment arm

Capecitabine DRUG

Capecitabine: 1000mg/m2 d1-14 q3w

Also known as: Xeloda

Treatment arm

5FU DRUG

400 mg/m2 (bolus) and 2400 mg/m2 (continuous infusion for 48hr)

Treatment arm

folinic acid DRUG

400 mg/m2 q2w

Treatment arm

Oxaliplatin DRUG

130 mg/m² q3w or 85 mg/m² q2w

Treatment arm

Irinotecan DRUG

180 mg/m² q2w and 200 mg/m² q3w

Treatment arm

Raltitrexed DRUG

2 mg/m² q2w and 3 mg/m² q3w

Treatment arm

Cetuximab DRUG

400 mg/m² q2w

Treatment arm

Bevacizumab DRUG

5 mg/kg q2w or 7.5mg/kg q3w

Treatment arm

Radiation RADIATION

25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation (pelvic radiation history) for pelvic recurrence tumor. 35-60Gy/5-8Fx irradiation for distance metastasis tumor.

Treatment arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is 18-75 years old at the time of signing the informed consent form.
• ECOG performance status 0-1.
• MRI/enhanced CT confirmed pelvic recurrence. According to RECIST 1.1, there is at least one measurable pelvic lesion.
• Distant metastasis lesions are no more than 5 and metastatic organ are no more than 3.
• No prior radiotherapy within 6 month.
• Previous system therapy. Patients Group Cohort A: participants with pelvic recurrence who have not previously been treated with first-line chemotherapy. Cohort B: Patients with disease progression or new lesions after first-line chemotherapy.
• Has an investigator determined life expectancy of at least 24 weeks.
• Demonstrate adequate organ function (bone marrow, liver, kidney and clotting function) within 7 days before the first administration without using blood products or hematopoietic stimulating factors.
• Non pregnant or lactating patients. Effective contraceptive methods should be used during the study and within 6 months of the last administration.
• Fully informed and willing to provide written informed consent for the trial.

You may not qualify if:

• Neutrophil \< 1.5×10\^9/L, PLT \< 100×10\^9/L (PLT \< 80×10\^9/L in patients with liver metastasis), or Hb \< 90g/L; blood transfusion within 2 weeks before enrollment is not allowed to meet the enrollment criteria.
• TBIL \> 1.5 ULN, or TBIL \> 2.5 ULN in patients with liver metastasis.
• AST or ALT \> 2.5 ULN, or ALT and / or AST \> 5 ULN in patients with liver metastasis.
• Cr \> 1.5 ULN, or creatinine clearance \< 50ml / min (calculated according to Cockcroft Gault formula).
• APTT \> 1.5 ULN, PT \> 1.5 ULN (subject to the normal value of the clinical trial research center).
• Serious electrolyte abnormalities.
• Urinary protein ≥ 2+, or 24-hour urine protein ≥1.0g/24h.
• Uncontrolled hypertension: SBP \>140mmHg or DBP \> 90mmHg.
• The presence of gastrointestinal diseases such as gastric or duodenal active ulcers, ulcerative colitis or unresected tumours with active bleeding; or other conditions likely to cause gastrointestinal bleeding or perforation; or unhealed gastrointestinal perforation or gastrointestinal fistula after surgical treatment.
• A history of arterial thrombosis or deep vein thrombosis within 6 months; a history of bleeding or evidence of bleeding tendency within 2 months.
• A history of heart disease within 6 months (including congestive heart failure, acute myocardial infarction, severe/unstable angina, coronary artery bypass grafting, cardiac insufficiency ≥ NYHA grade 2 and LVEF\<50%).
• Uncontrolled malignant pleural effusion, ascites, or pericardial effusion.
• History of anti-PD-1, PD-L1, PD-L2, CTLA-4 or any other specific T cell co-stimulation or checkpoint pathway targeted therapy.
• The presence of a clinically detectable second primary malignancy, or history of other malignancies within 5 years excluding adequately treated non-melanoma skin cancer, carcinoma in situ of cervix and superficial bladder tumour (non-invasive tumour, or carcinoma in situ, or T1).
• A history of liver disease including, but not limited to HBV infection or HBV DNA positive(≥1×10\^4/ml), HCV infection or HCV DNA positive(≥1×10\^3/ml) and liver cirrhosis.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Related Publications (1)

• Wan J, Wu R, Fu M, Shen L, Zhang H, Wang Y, Wang Y, Zhou S, Chen Y, Xia F, Zhang Z. TORCH-R trial protocol: hypofractionated radiotherapy combined with chemotherapy and toripalimab for locally recurrent rectal cancer: a prospective, single-arm, two-cohort, phase II trial. Front Oncol. 2023 Nov 20;13:1304767. doi: 10.3389/fonc.2023.1304767. eCollection 2023.

  PMID: 38053659 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

spartalizumab; toripalimab; Capecitabine; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan; raltitrexed; Cetuximab; Bevacizumab; Radiation

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Physical Phenomena

Study Officials

• Zhen Zhang, MD PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhen Zhang, MD PhD

CONTACT

18801735029; zhen_zhang@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 17, 2022
• First Posted: November 28, 2022
• Study Start: November 30, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: October 1, 2024

Record last verified: 2024-09

Locations

CN (1)