Neoplasms

Digestive System Diseases

All Conditions

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Capecitabine

Immunomodulating Agents

Oxaliplatin

Immunoglobulins

Antimetabolites

Participants will receive 5\*5Gy node-sparing short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with total neoadjuvant CAPOX and sintilimab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and sintilimab, 200mg intravenous infusion d1 of each cycle. CAPOX and sintilimab are repeated every 3 weeks for 8 cycles. Patients with cCR will be managed with a WW strategy, and patients who did not achieve cCR will receive TME surgery.

Interventions:

* Radiation: node-sparing short-course radiation
* Drug: PD-1 antibody (Sintilimab)
* Drug: Capecitabine
* Drug: Oxaliplatin

5Gy\*5d, radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes

node-sparing short-course radiotherapy

200mg intravenous infusion d1 of each cycle\*8cycles

Sintilimab

1000mg/m2, PO, BID, d1-14 of each cycle\*8cycles

130mg/m2, intravenous infusion,d1 of each cycle\*8cycles

laparoscopic or robotic TME surgery for non-cCR patients

TME surgery

watch and wait

jinlin du, master

cheng cai, master

Cheng Cai, master

Jinlin Du, master

phase II clinical trial to evaluate node-sparing short-course radiation combined with total neoadjuvant CAPOX and Sintilimab for MSS locally advanced rectal cancers.

This is an open-label, prospective, single-center phase II clinical trial to evaluate node-sparing short-course radiation (Radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) combined with total neoadjuvant CAPOX and PD-1 Inhibitor (Sintilimab) for patients with MSS locally advanced of middle and low rectal cancer. A total of 47 patients will be enrolled in this trial. The primary endpoint is the complete response(CR) rate, which includes cCR and pCR. The organ preservation rate, tumor regression grade, 3-year DFS, 3-year OS, and adverse effects will also be analyzed.

Radiation: node-sparing short-course radiotherapy (5Gy\*5d) Drug: PD-1 antibody (Sintilimab) Drug: Capecitabine Drug: Oxaliplatin

Node-sparing Radiotherapy Combined With Total Neoadjuvant CAPOX and Sintilimab for MSS Middle and Low Rectal Cancer

Total Neoadjuvant CAPOX And PD-1 Inhibitor（Sintilimab） Combined With Node-sparing Short-course Radiotherapy For MSS Locally Advanced Of Middle And Low Rectal Cancer(CASINOs): An Open Label, Single-arm, Prospective Clinical Trial

JinhuaCH will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.

Pathological complete response (pCR) ：absence of residual tumour on resected specimen. Clinical complete response（cCR）: no residual tumour visible on imaging or colonoscopy and biopsy.

TRG is evaluated according to the AJCC system. TRG0-1 is defined as good response, TRG2 as moderate response, and TRG3 as poor response.

Presence of adenocarcinoma within the rectal wall or within the mesorectum confirmed by pathology.

the time from randomization to recurrence of tumor or death

Rate of radiotherapy, chemotherapy and immunotherapy related adverse events

Rectal specific quality of life according to European Organization for Research and Treatment of Cancer ( EORTC) Quality of life questionnaire QLQ-CR29. scale from 0 to 100, A higher scale represents better function and a higher quality of life.

Quality of life according to EORTC Quality of life Questionnaire QLQ-C30 version 3.0. Score range from 0 to 100 points. A higher score represents better function and a higher quality of life.

The change of severity of fecal incontinence assessment according to Wexner score. a score from 0-20, where 0 is perfect continence and 20 is complete incontinence.

Jinhua Central Hospital

Clinical Professor

Rare Diseases

Stomach Neoplasms

Stomach Diseases

Stomach Cancer

Tegafur

Apatinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Sintilimab Plus Apatinib and Chemotherapy in Patients with Previously Untreated HER-2 negative MSS Advanced or Metastatic GC or GEJ Cancer

for 2-6 cycles followed by Sindilizumab plus Tegafur gimeracil oteracil potassium capsules.

Sintilimab 200 mg, intravenously (IV) every 3 weeks(Q3W)

Zhao Jiuda, MD

Zhao Jiuda

To evaluate the efficacy and safety of Sintilimab combined with apatinib and chemotherapy as First-line or second-line Therapy in Treatment of HER-2 negative MSS Advanced or Metastatic GC or GEJ Cancer. At the same time, the correlation between tissue programmed death ligand-1(PD-L1) expression and blood circulating tumor cell(CTC) counts and the efficacy of immune combination therapy was also explored.

Participants receive Sintilizumab 200 mg, intravenously (IV) every 3 weeks(Q3W);plus Apatinib 250 mg twice daily (BID) by continous oral adminstration for 14 days, followed by a recovery period of 7 days; plus Tegafur gimeracil oteracil potassium capsules (40mg for body surface area \< 1.25/m\^2, 50mg/m\^2 for body surface area 1.25-1.5m\^2, 60mg for body surface area \> 1.5/m\^2) BID by continous oral adminstration for 14 days, followed by a recovery period of 7 days, plus Oxaliplatin 85 mg/m\^2, IV Q3W; for 4-6 cycles followed by Cindilizumab plus Tegafur gimeracil oteracil potassium capsules.

Patients who meet the inclusion criteria will receive with sintilimab combined with apatinib and chemotherapy(Oxaliplatin plus Tegafur gimeracil oteracil potassium capsules). At the same time, tumor samples were collected for tissue PD-L1 detection and blood samples for CTC detection according to the wishes of patients.

Patients underwent contrast-enhanced thoracoabdominal and pelvic Computer Tomography(CT) at baseline and every 6 weeks after enrollment. Patients with stable or remission after 2 to 6 cycles of combined treatment can reduce the evaluation frequency to once every 12 weeks during the maintenance treatment period.

A Study to Evaluate the Efficacy and Safety of Sintilimab Plus Apatinib and Chemotherapy in Patients With HER-2 Negative Microsatellite Stability (MSS) Advanced or Metastatic Gastric (GC) or Gastroesophageal Junction (GEJ) Cancer

An Open-Label, Multi-Center, Phase II Study to Evaluate the Efficacy and Safety of PD-1 Antibody Sintilimab Plus Apatinib and Chemotherapy in Patients With HER-2 Negative MSS Advanced or Metastatic GC or GEJ Cancer

per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Number of Subjects with treatment-related adverse events

The Second Hospital of Lanzhou University

Jiuda Zhao

Professor

Colonic Diseases

Antibodies, Monoclonal

recombinant humanized anti-PD-1 monoclonal antibody for injection (JS001) in combination with regorafenib tablet

JS001

regorafenib tablet

Rui-hua Xu, PhD

Colorectal cancer is one of the most common malignancies in China. Regorafenib is the standard multi-kinase inhibitor for refractory advanced colorectal cancer. In mice, regorafenib combined with anti-PD-1 was shown superior to regorafenib, which has not yet been verified in humans. JS001 is the Chinese anti-PD-1 monoclonal antibody for injection which has been approved for melanoma. This study is the first multi-center, open-label, phase I/II clinical trial to evaluate tolerability, safety and efficacy of JS001 in combination with regorafenib tablet in patients with MSS/MSI-L/pMMR, relapsed or metastatic colorectal cancer who have failed or can not tolerate fluorouracil, oxaliplatin and irinotecan based systemic treatment. The phase I clinical trial is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of regorafenib tablet in this regimen, and select an acceptable safe dose for the phase II clinical trial to further determine safety and efficacy of this combination regimen in patients with metastatic colorectal cancer.

Colorectal cancer is one of the most common malignancies in China, with incidence and mortality ranking the 3rd and 4th among malignancies in China. Regorafenib is the standard multi-kinase inhibitor for refractory metastatic colorectal cancer, with multiple anti-tumor effects by inhibiting targets related to tumor cell proliferation, tumor metastasis, tumor angiogenesis and tumor immune escape, howerver, its efficacy is limited. Immunotherapy has become standard treatment for mCRC patients with MSI-H/dMMR. Combination of anti-angiogenesis treatment and immunotherapy may have a better anti-tumor effect. In mice, regorafenib combined with anti-PD-1 was shown superior to regorafenib, which has not yet been verified in humans. JS001 is the Chinese anti-PD-1 monoclonal antibody for injection which has been approved for melanoma. This study is the first multi-center, open-label, phase I/II clinical trial to evaluate tolerability, safety and efficacy of JS001 in combination with regorafenib tablet in patients with MSS/MSI-L/pMMR, relapsed or metastatic colorectal cancer who have failed or can not tolerate fluorouracil, oxaliplatin and irinotecan based systemic treatment. The phase I clinical trial is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of regorafenib tablet in this regimen, and select an acceptable safe dose for the phase II clinical trial to further determine safety and efficacy of this combination regimen in patients with metastatic colorectal cancer.

JS001 Combined With Regorafenib in Patients With Advanced Colorectal Cancer

A Multi-center, Open-label, Phase I/II Clinical Trial of Tolerability, Safety and Efficacy of Recombinant Humanized Anti-PD-1 Monoclonal Antibody for Injection (JS001) Combined With Regorafenib in Patients With Advanced Colorectal Cancer

The maximum dose that patients enrolled can tolerate during dose escalation of phase I clinical trial according to mTPI method

Severe toxicity that may be related to JS001 or regorafenib during dose escalation of phase I clinical trial according to mTPI method

The ratio of patients who are evaluated as CR or PR

The Kaplan-Meier survival from the initiation date of first cycle until the date of first documented progression or date of death

The Kaplan-Meier survival from the initiation date of first cycle until death from any cause or the last follow-up date.

Defined as the proportion of patients whose tumors shrink or remain stable for a certain period of time, including CR, PR and SD.

defined as the time between the first assessment of a tumor as PR or CR and the first assessment as PD or any cause of death

The dynamic variation of circulating free DNA or cell free DNA (cfDNA) in immunotherapy efficacy and safety assessment

The composition of intestinal microorganism pre- and post-treatment tested by intestinal microorganism, the relationship between intestinal flora alpha diversity and beta diversity and immunotherapy response as well as between intestinal microorganism alpha diversity and beta diversity and treatment toxicity and tolerance.

Shanghai Junshi Bioscience Co., Ltd.

Sun Yat-sen University

Professor, Principal Investigator, President

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Herbal and Botanical

Nivolumab

Relatlimab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Cola

480mg/ 960mg or 480mg/480mg (sequential administration)

Patients will receive treatment every 28 days for up to 2 years. Nivolumab will be administered IV on day 1 (28 day cycle).

Patients will receive treatment every 28 days up to 2 years. Relatlimab will be administered IV on day 1 (28 day cycle).

Dung Le, MD

The purpose of this study is to evaluate the safety and clinical activity of nivolumab and relatlimab in patients with metastatic or locally advanced microsatellite stable (MSS) colorectal cancer.

Study of Nivolumab and Relatlimab in Patients With Microsatellite Stable (MSS) Advanced Colorectal Cancer

Phase A Phase 2 Study Evaluating Response and Biomarkers in Patients With Microsatellite Stable (MSS) Advanced Colorectal Cancer Treated With Nivolumab in Combination With Relatlimab

The proportion of subjects with partial response (PR) or complete response (CR) according to RECIST 1.1.

Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Node-sparing Radiotherapy Combined With Total Neoadjuvant CAPOX and Sintilimab for MSS Middle and Low Rectal Cancer	NCT06204094	Locally Advance...	node-sparing sh... Sintilimab Capecitabine Oxaliplatin TME surgery watch and wait	18 Years - 75 Years	Jinhua Central Hospital
A Study to Evaluate the Efficacy and Safety of Sintilimab Plus Apatinib and Chemotherapy in Patients With HER-2 Negative Microsatellite Stability (MSS) Advanced or Metastatic Gastric (GC) or Gastroesophageal Junction (GEJ) Cancer	NCT05216237	Gastric Cancer Chemotherapy Immunotherapy	Sintilimab 200 ...	18 Years - 75 Years	Affiliated Hospital of Qinghai University
JS001 Combined With Regorafenib in Patients With Advanced Colorectal Cancer	NCT03946917	Colorectal Canc...	JS001 regorafenib tab...	18 Years -	Sun Yat-sen University
Study of Nivolumab and Relatlimab in Patients With Microsatellite Stable (MSS) Advanced Colorectal Cancer	NCT03642067	Microsatellite ... Colorectal Aden...	Nivolumab Relatlimab Nivolumab Relatlimab	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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