SCRT Followed by Camrelizumab Combined With Fluzoparib and Chemotherapy as Neoadjuvant Therapy for LARC

NCT06516445 | Recruiting Phase 2

• 1 other identifier: MA-CRC-II-007
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

To explore the safety and efficacy of neoadjuvant therapy for locally advanced rectal cancer with short course radiotherapy followed by camrelizumab combined with fluzoparib and chemotherapy

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Adverse events

  Incidence and grade according to NCI-CTCAE 5.0(including serious adverse events and immune-related adverse events); Surgical safety: surgical complications, 30 - and 90-day postoperative mortality, length of stay, and reoperation rate

  up to 36 months

• pCR (Pathological Complete Response)

  The proportion of subjects with no residual viable tumor cells(ypT0N0) in the primary tumor and lymph nodes, also defined as the proportion of subjects with grade 0 in the AJCC Tumor Regression Grading (TRG) scoring system(version 8.0).

  up to 6 months

Secondary Outcomes (6)

• 3-year Event-Free Survival(EFS) rate

  up to 36 months

• Overall Survival(OS)

  up to 36 months

• R0 resection rate

  up to 6 months

• Completion rate of neoadjuvant therapy

  up to 6 months

• Tumor Regression grade (TRG)

  up to 6 months

Other Outcomes (1)

• biomark

  up to 36 months

Study Arms (1)

SCRT followed by camrelizumab combined with fluzoparib and chemotherapy

EXPERIMENTAL

Radiation: SCRT; Drug: Camrelizumab; Drug: Fluzoparib; Drug: CAPEOX

Interventions

SCRT RADIATION

5×5Gy，5Gy/d，QD，D1-D5

SCRT followed by camrelizumab combined with fluzoparib and chemotherapy

Camrelizumab DRUG

200mg, D1, ivgtt, Q3W, C1-4

SCRT followed by camrelizumab combined with fluzoparib and chemotherapy

Fluzoparib DRUG

100mg, BID, PO, Q3W, C1-4

SCRT followed by camrelizumab combined with fluzoparib and chemotherapy

CAPEOX DRUG

Capecitabine: 1000 mg/m2, BID, PO，D1-14, Q3W, C1-C4； Oxaliplatin: 130mg/m2, D1, ivgtt, 0-2h，Q3W，C1-4

SCRT followed by camrelizumab combined with fluzoparib and chemotherapy

Eligibility Criteria

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

You may qualify if:

• Patients who provided written informed consent form for participation in this study;
• Aged 18-75 years old, male or female;
• Histologically confirmed pathological diagnosis of proficient mismatch repair/microsatellite stable(pMMR/MSS) rectal adenocarcinoma;
• The lower margin of the tumor is ≤10cm from the anal verge;
• Clinical Stage (according to the 8th edition of AJCC) T3NanyM0 and confirmed on imaging to fulfil at least any of the following: （1）MRF (+)，（2）EMVI（+），（3）LPLN（+）；or T4NanyM0 with or without one of the above three;
• Those who are expected to achieve R0 resection;
• Able to swallow tablets normally;
• Patients with the ECOG performance status of 0 or 1 at the time of enrollment;
• Patients have not received any previous anti-tumor therapy for rectal cancer;
• Planning to undergo surgery after completion of neoadjuvant therapy;
• Have no contraindications to surgery;
• Normal function of major organs, including:
• Routine blood tests (no blood components, cell growth factors, leukocyte boosters, platelet boosters, or anaemia-correcting drugs will be allowed within 14 days prior to the first dose of study drug):White blood cell count ≥ 4.0 x 109/L; Neutrophil count ≥ 1.5 x 109/L; Platelet count ≥100×109/L; Hemoglobin ≥90 g/L
• Blood biochemistry: Total bilirubin ≤ 1.5 x ULN; ALT ≤ 2.5×ULN, AST ≤ 2.5×ULN; Serum creatinine ≤ 1.5 x ULN, or creatinine clearance ≥ 50 mL/min (Cocheroft-Gault formula)
• Coagulation: International normalised ratio (INR) ≤ 1.5 x ULN; Activated partial thromboplastin time (APTT) ≤ 1.5×ULN

You may not qualify if:

• A pre-existing history of allergy to monoclonal antibodies, any component of camrelizumab, fluzoparib, capecitabine, oxaliplatin, or other platinum-based drugs;
• Has received, or is receiving, any of the following prior treatments：a) Any radiotherapy, chemotherapy, or other antineoplastic drug directed against the tumor; b) Treatment with immunosuppressive drugs, or systemic hormonal drugs for immunosuppression (doses \> 10 mg/day prednisone or equivalent) within 2 weeks prior to first use of study drug; inhaled or topical steroids and adrenocorticotropic hormone replacement at doses \> 10 mg/day prednisone or equivalent are permissible in the absence of active autoimmune disease; c) Received a live attenuated vaccine within 4 weeks prior to first use of study drug; d) Major surgery or severe trauma within 4 weeks prior to first use of study drug;
• A history of immunodeficiency, including a positive HIV test, or other acquired or congenital immunodeficiency disease, or a history of organ transplantation or allogeneic bone marrow transplantation;
• Presence of cardiac clinical conditions or diseases that are not well controlled, including, but not limited to, such as (1) NYHA Class II or higher heart failure, (2) unstable angina pectoris, (3) myocardial infarction within 1 year, and (4) clinically significant supraventricular or ventricular arrhythmia that is not clinically intervened with or that remains poorly controlled after clinical intervention;
• A serious infection (CTCAE \> grade 2) within 4 weeks prior to first use of study drug, such as severe pneumonia, bacteremia, or infectious co-morbidities requiring hospitalisation; except for prophylactic antibiotics if baseline chest imaging suggests active lung inflammation, signs and symptoms of infection within 14 days prior to first use of study drug, or if oral or intravenous antibiotic therapy is required ;
• The presence of active tuberculosis infection by history or CT scan, or a history of active tuberculosis infection within 1 year prior to enrolment, or a history of active tuberculosis infection more than 1 year ago without regular treatment
• Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (hepatitis C antibody positive and HCV RNA above the lower detection limit of the analytical method);
• Other malignancies diagnosed within 5 years prior to the first use of study drug, unless malignancies with a low risk of metastasis or risk of death (5-year survival \>90%), such as adequately treated basal cell carcinoma of the skin or squamous cell skin carcinoma or carcinoma in situ of the uterine cervix, may be considered for enrolment;
• Women during pregnancy or lactation;
• In the judgement of the investigator, the presence of other factors that may lead to forced termination of the study in the middle of the study, such as the presence of other serious illnesses (including psychiatric illnesses) that require comorbid treatment, alcoholism, drug abuse, family or social factors that may affect the safety of or compliance with the subject.

Sponsors & Collaborators

• Huazhong University of Science and Technology: lead

Study Sites (1)

Tongji hospital, Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, 430079, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

camrelizumab; fluzoparib

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Xianglin Yuan

CONTACT

13667241722; xlyuan1020@163.com

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: Huazhong University of Science and Technology

Study Record Dates

• First Submitted: July 9, 2024
• First Posted: July 24, 2024
• Study Start: June 28, 2023
• Primary Completion: June 28, 2025
• Study Completion (Estimated): June 28, 2026
• Last Updated: July 24, 2024

Record last verified: 2024-07

Locations

CN (1)