Neoplasms

Digestive System Diseases

All Conditions

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Sintilimab combined withTotal Neoadjuvant Treatment

Sintilimab

There have been many high-quality research publications, including the TNT model of short-term radiotherapy combined with consolidation chemotherapy, and the TNT model of three-drug combination with neoadjuvant chemotherapy with higher treatment intensity combined with CRT. All have achieved better tumor regression and tumor regression than the standard CRT model. The higher pCR rate reduces the recurrence and metastasis events, improves the prognosis, and strives for more opportunities for organ function preservation. Can the TNT model combined with immunotherapy further increase the cCR rate? Whether immunotherapy can bring further survival benefits to patients who develop CR after neoadjuvant therapy (especially W\&W after cCR), it is also necessary to carry out corresponding clinical research. We designed this study for patients with mid-to-low and locally advanced rectal cancer who want to be able to preserve the anus. TNT mode combined with PD-1 immunotherapy is given before surgery, and TME surgery is performed on patients who have not reached cCR or who still require surgery. It provides sufficient evidence for the safety and effectiveness of preoperative neoadjuvant therapy for PD-1 in low- and middle-level locally advanced rectal cancer.

Total Neoadjuvant Treatment Plus PD-1 in Mid-Low Locally Advanced Rectal Cancer

Total Neoadjuvant Treatment Plus PD-1 in Mid-Low Locally Advanced Rectal Cancer (STARS-RC03)

Any treatment-related grade 3 or higher non-hematological adverse event determined by CTCAE version v 4.03.

defined as cCR or pCR achieved after neoadjuvant therapy.

NAR score is a continuous scale with 24 possible discrete scores, ranging from 0 to 100. In this patient cohort, low scores were defined as \<8, median values were 8-16, and high scores were\> 16, and the corresponding 5-year OS was 92%, 89%, and 68%, respectively. A higher score is associated with a worse prognosis.

It is defined as the time of death, local recurrence after radical resection, and any form of distant metastasis within 3 years from the date of receiving neoadjuvant therapy. The local regeneration of the tumor that can be rescued after non-surgical treatment is not regarded as a local recurrence, nor is it counted as a positive event.

QLQ-C30（Quality of Life Questionnaire C30）

QLQ-C29(Quality of Life Questionnaire C29）

LARS score（Low Anterior Resection Syndrome Questionnaire）

IPSS score（International Prostate Symptom Score）

CIPE （Chinese Index of sexual Function for premature Evaluation,CIPE）score

IIEF-5(international questionnaire of erectile function-5)score

The First Hospital of Jilin University

A customized tumor-informed ctDNA test that, after receiving the tumor tissue, examines whole exome sequencing of a biopsied tumor to find the somatic tumor-derived mutations. From those mutations, the 16 most clonal mutations are used to create a personal assay

SignateraTM assay

Smitha Krishnamurthi, MD

The purpose of this study is to use the SignateraTm assay created from rectal tumor biopsies to monitor participants' blood for fragments of DNA shed by tumor cells. The tumor DNA fragments are referred to as circulating tumor DNA, or ctDNA for short.

Rectal cancer tissue samples that were collected from participants' previous biopsies will be sent to Natera for Signatera assay creation after enrollment onto the study.

One 6 mL tube of blood will be obtained at baseline prior to initiation of treatment. Blood will also be obtained in two 6 tubes at the following points: 3-4 weeks into chemoradiation therapy (CRT), after CRT, after chemotherapy, after surgery for those who undergo resection, and during surveillance 3 months after surgery or at the end of treatment for one year after completion of TNT (total neoadjuvant therapy).

The primary objective of the study is to estimate the percentage of patients with positive ctDNA at the end of TNT .

The secondary objectives of the study include:

1. Estimating the change in ctDNA after chemoradiation and chemotherapy
2. Characterize the correlation of complete response to TNT with presence or absence of ctDNA
3. Describe the recurrence rate in participants with and without ctDNA after TNT
4. Characterize the correlation of ctDNA at end of TNT with recurrence free survival at 2 years.

Formalin-fixed, paraffin embedded tissue from the patient's colonoscopy or flexible sigmoidoscopy in surgeon's office will be sent to Natera for Signatera assay creation after enrollment onto the study

Blood will be collected in Ethylenediamine tetraacetic acid (EDTA) tubes and sent to Natera via shipping materials provided by Natera.

Circulating Tumor DNA to Monitor the Efficacy of Total Neoadjuvant Therapy for Rectal Cancer

The recurrence rate (local and distant) is the number of participants with positive ctDNA and negative ctDNA after TNT for both participants who undergo watch and wait and those who have surgery. Non operative management (watch and wait) is offered to participants who have a complete clinical response who will comply with required surveillance. Outcomes will be recorded and described for all participants, those who underwent surgery and those who underwent non-operative management.

The presence or absence of ctDNA with relapse-free survival.Time to event variable will be summarized using the Kaplan-Meier method. Outcomes will be recorded and described for all patients, those who underwent surgery and those who underwent non-operative management.

The percentage of participants with detectable ctDNA at the completion of TNT

The change in ctDNA (continuous and categorical positive/negative) during and at the end of neoadjuvant chemoradiation and with chemotherapy will be measured. Continuous measurements will be summarized using medians and ranges. Categorical factors will be summarized using frequencies and percentages. Changes in ctDNA will be analyzed by using the Mann-Whitney U test or the Fisher's exact test for continuous or categorical variables, respectively.

Correlation of complete response to TNT defined by presence or absence of ctDNA.

Case Comprehensive Cancer Center

Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Oxaliplatin

The interventions of experimental group include 1 cycle of CAPOX before radiotherapy; and then start concurrent chemoradiotherapy with CAPOX regimen (capecitabine: 825mg/m2, bid, 5d/w; oxaliplatin, 130mg/m2, D1, q3w) for 2 cycles followed by 3 cycles of CAPOX 2-3 weeks after the completion of radiotherapy. Intensity modulated radiotherapy (IMRT/VMAT) was used for radiotherapy, and the dose was 50-50.4Gy/25-28f, 1.8-2.0Gy/d, 5f/w. The TME operation will be given 3-4 weeks after the end of the total neoadjuvant treatment.

The interventions of control group is standard preoperative concurrent chemoradiotherapy. The radiotherapy target areas and dosage are the same as group TNT. During radiotherapy, only oral capecitabine will be delivered and capecitabine dose was 825mg/m2, bid, 5d/w. The TME surgery will be performed 6-8 weeks after the end of concurrent chemoradiotherapy. Then, patients will receive another 6 cycles of CAPOX.

The interventions of experimental group include 1 cycle of CAPOX before radiotherapy; and then start concurrent chemoradiotherapy with CAPOX regimen (capecitabine: 825mg/m2, bid, 5d/w; oxaliplatin, 130mg/m2, D1, q3w) for 2 cycles followed by 3 cycles of CAPOX 2-3 weeks after the completion of radiotherapy. Intensity modulated radiotherapy (IMRT/VMAT) was used for radiotherapy, and the dose was 50-50.4Gy/25-28f, 1.8-2.0Gy/d, 5f/w.

Total neoadjuvant treatment

concurrent chemoradiotherapy

The TME operation will be given after the end of the neoadjuvant treatment.

Patients will receive another 6 cycles of CAPOX after TME.

Adjuvant chemotherapy

Ziqiang Wang

Xin Wang

Ziqiang Wang, MD

Kefeng Ding, MD

Purpose:To compare the efficacy and the safety of total neoadjuvant chemotherapy + TME with standard neoadjuvant concurrent chemoradiotherapy + TME + adjuvant chemotherapy for locally advanced rectal cancer patients with high risk factors of recurrence.

Evaluation indexes: (1) the primary evaluation index: disease-free survival (disease free survival, DFS); (2) the secondary evaluation indexes: pathological complete remission rate (pCR), the 3 year overall survival (overall survival, OS); R0 dissection rate; distant metastasis free survival (DMFS); local recurrence free survival rate (LRRFS); tumor regression grade (TRG, tumor regression grade) and the adverse reaction rate during the chemotherapy, the operation safety index; quality of life; psychological and cognitive effects, assessment of nutritional status.

Safety evaluation indexes: including all adverse events observed during the experiment.

Number of patients: 458 cases Study design: patients will be randomly assigned into the total neoadjuvant treatment group (experimental group, TNT) and neoadjuvant concurrent chemotherapy group (control group, CRT) in the ratio of 1: 1. The patients of experimental group will be given 1 cycle of induction CAPOX (Oxaliplatin 130mg/m2 d1, Capecitabine 1000mg/m2, bid, d1-14) prior to radiotherapy. Then pelvic IMRT/VMAT (50-50.4Gy/25-28f) and two cycles of concurrent chemotherapy (Oxaliplatin 130mg/m2, d1, d 22, Capecitabine 825mg/m2, bid, 5d/w, 25-28d) are performed. And three cycles of consolidation chemotherapy (CAPOX) are delivered after concurrent chemoradiotherapy. Total mesorectal excision (TME) is performed after completion of the whole neoadjuvant treatment. The patients of control group will receive standard concurrent neoadjuvant chemoradiotherapy with capecitabine (825mg/m2, bid, 5d/w) followed by TME 6-8 weeks after the end of concurrent chemoradiotherapy. Then, patients are treated with another 6 cycles of CAPOX.

Schedule: Investigators plan to finish the study in 4 years and write the related work within 2 years after the completion of this study.

Total Neoadjuvant Treatment vs. Chemoradiotherapy in Local Advanced Rectal Cancer With High Risk Factors

Total Neoadjuvant Treatment Versus Conventional Neo-chemoradiotherapy in Locally Advanced Rectal Cancer With High Risk Factors: a Multicenter Randomized Phase III Clinical Study.

Time from the completion of the treatment to any recurrences or distant metastases

The rate of complete remission patients to all resected patients

The rate of patients alive 3 years after the completion of treatment

The rate of patients who received R0 dissection to all the patients

Time from the completion of the treatment to any distant metastases

The rate of patients without local recurrence to all the patients

The level of tumor regression under pathological examination

The psychological and cognitive changes of patients after treatment

West China Hospital

Professor

Patients will receive 2 CAPOX cycles, followed by short-course radiotherapy and 4 CAPOX cycles.

Approach

Juliana Souza

Isabele Small

Luana Cerva

Juliana O Souza, MD

Short-course radiotherapy followed by consolidation chemotherapy has shown a better response rate when compared to chemoradiotherapy treatment.

In addition, recent studies have shown better tolerance with total neoadjuvant treatment, with induction or consolidation chemotherapy. Induction chemotherapy could reduce the size of the tumor, treat micrometastases early and allow treatment to start immediately (avoiding potential delays in waiting for radiotherapy). While consolidation chemotherapy allows longer waiting times for surgery, with higher response rates.

Methods: This trial aim to evaluate induction treatment with CAPOX, followed by short-course radiotherapy consolidation chemotherapy with CAPOX. After 5-7 weeks, patients will be evaluate by MRI. Patients with incomplete clinical response will be referred to immediate surgery and patients with complete clinical response will be managed with "watch and wait" approach. Patients with progression disease during the treatment phase will be withdrawn from the study and will receive their treatment according to the investigator's judgment.

The sample size was calculated according to Simon's optimal two-stage design. Accordingly, 21 patients must be included in each group during the first stage and 24 during the second stage. Treatment regimen will be considered effective if 9 or more patients show good response (final analysis), reaching 80% power with an alpha of 0.10 level of significance.

Short-course Radiotherapy With Induction and Consolidation Chemotherapy in Patients With Locally Advanced Rectal Cancer

Phase II Study of Short-course Radiotherapy With Induction and Consolidation Chemotherapy in Patients With Locally Advanced High-risk Rectal Cancer

Good response rate is defined as the proportion of patients who reached mrTRG 1 or 2 and the absence of remote disease in the reevaluation period, with the denominator being the total number of patients who started total neoadjuvant treatment.

defined as the time from the date of MRI of the pelvis of the reassessment period to relapse, death or last contact date.

defined as the time from the date of the induction chemotherapy until the death or date of last contact

Incidence of adverse events (AEs), serious AEs, deaths and laboratory abnormalities in participants who received at least one dose of study treatment

Instituto Nacional de Cancer, Brazil

Antimetabolites

Drug: Neoadjuvant chemotherapy Capeox (Capecitabine + Oxaliplatin), 6 cycles; adjuvant chemotherapy, Capecitabine, 2 cycles or physicians' decision.

External beam radiotherapy: Neoadjuvant, 50 Gy, 2 Gy/session; 25 fractions. Procedure: 'Watch and wait strategy' or surgery including local excision, intersphincter resection or total mesorectal excision or other kinds of surgeries.

Capecitabine, Oxaliplatin

External beam radiotherapy to the primary tumor, regional lymph nodes and clinical target volume

External beam radiotherapy

'Local excision' or 'Intersphincter resection' or 'Total mesorectal excision' or other surgeries

Surgery

Watch and wait strategy recommendation and discussion for cCR patients

Watch and wait strategy

WeiWei Xiao

This is a open-label, single-arm study to investigate the safety and efficacy of total neoadjuvant treatment (TNT) in patients with locally advanced resectable rectal cancer.

Standard treatment of rectal cancer is neoadjuvant capecitabine chemotherapy with radiotherapy, followed by total mesorectal excision.

A new concept suggests organ preservation as an alternative to rectal excision in good responders after neoadjuvant radiochemotherapy to decrease surgical morbidity and increase quality of life.

The rational is the fact that 15%-20% of patients have sterilized tumours after chemoradiotherpay for locally advanced rectal cancer. As compared to capecitabine alone, oxaliplatin and more intensified chemotherapy have been shown to increase tumor regression in the neoadjuvant chemoradiation setting. Meanwhile, prolong of time interval from the end of radiotherapy to assessment of tumor response could further increase pathologic complete response rate and complete clinical response rate.

The objective of this trial is to increase the rate of clinical complete response for distal rectal cancer patients by optimizing tumour response. The investigators expect to increase chance of clinical complete response by using total neoadjuvant treatment regimen as compared to conventional chemoradiotherapy alone.

TNT to Increase the Clinical Complete Response Rate for Distal LARC

Total Neoadjuvant trEatment to Increase the Clinical Complete reSponse Rate for diStal Locally Advanced Rectal Cancer (TESS)

Number of patients with sphincter preservation through Watch and wait strategy, or local excision, or intersphincter resection, or low anterior resection, etc.

Rate of pathological complete response and tumor regression grade distribution

Long-term anal function according to Wexner Continence Grading Scale

Long-term toxicity grading according to CTCAE 5.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Total Neoadjuvant Treatment Plus PD-1 in Mid-Low Locally Advanced Rectal Cancer	NCT04906044	Tislelizumab Locally Advance... Total Neoadjuva... PD-1	Sintilimab	18 Years - 80 Years	The First Hospital of Jilin University
Circulating Tumor DNA to Monitor the Efficacy of Total Neoadjuvant Therapy for Rectal Cancer	NCT05356585	Colorectal Canc... Rectal Cancer	SignateraTM ass...	18 Years -	Case Comprehensive Cancer Center
Total Neoadjuvant Treatment vs. Chemoradiotherapy in Local Advanced Rectal Cancer With High Risk Factors	NCT03177382	Total Neoadjuva... Chemoradiothera... Local Advanced ... High Risk Facto...	Total neoadjuva... concurrent chem... TME Adjuvant chemot...	18 Years - 70 Years	West China Hospital
Short-course Radiotherapy With Induction and Consolidation Chemotherapy in Patients With Locally Advanced Rectal Cancer	NCT04674696	Rectal Cancer Total Neoadjuva...	Approach	18 Years - 75 Years	Instituto Nacional de Cancer, Brazil
TNT to Increase the Clinical Complete Response Rate for Distal LARC	NCT03840239	Rectal Cancer Rectal Cancer S... Rectal Cancer S... Chemoradiation	Capecitabine, O... External beam r... Surgery Watch and wait ...	18 Years - 70 Years	Sun Yat-sen University
TNT to Increase the Clinical Complete Response Rate for Distal LARC	NCT03840239	Rectal Cancer Rectal Cancer S... Rectal Cancer S... Chemoradiation	Capecitabine, O... External beam r... Surgery Watch and wait ...	18 Years - 70 Years	Sun Yat-sen University
Short-course Radiotherapy With Induction and Consolidation Chemotherapy in Patients With Locally Advanced Rectal Cancer	NCT04674696	Rectal Cancer Total Neoadjuva...	Approach	18 Years - 75 Years	Instituto Nacional de Cancer, Brazil
Total Neoadjuvant Treatment Plus PD-1 in Mid-Low Locally Advanced Rectal Cancer	NCT04906044	Tislelizumab Locally Advance... Total Neoadjuva... PD-1	Sintilimab	18 Years - 80 Years	The First Hospital of Jilin University

Spots Global Cancer Trial Database for total neoadjuvant treatment