Neoplasms

Digestive System Diseases

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Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Niraparib

Dostarlimab

Immunoglobulins

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

niraparib, 100 mg orally once daily for up to 12 weeks dostarlimab, 500 mg infused (IV) once every 3 weeks for up to 12 weeks radiation therapy, 5 Gray (Gy) per day for 5 consecutive days

niraparib, 200 mg orally once daily for up to 12 weeks dostarlimab, 500 mg infused (IV) once every 3 weeks for up to 12 weeks radiation therapy, 5 Gray (Gy) per day for 5 consecutive days

Niraparib is a drug FDA-approved for use in maintenance treatment of adults with advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.

Dostarlimab, sold under the brand name Jemperli, is a monoclonal antibody medication used for the treatment of endometrial cancer.

Participants will be treated with intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) to minimize mean dose to femoral, pelvic, and lumbar bone marrow. The entire mesorectum will be treated to a total dose of 25 Gy.

Short course radiation

Joseph M. Caster, M.D., Ph.D.

Saima Sharif, M.D.

Sandy Vollstedt, RN, BSN, OCN

Heather Brown, RN, BAN, OCN

Joseph M Caster, MD, PhD

Saima Sharif, MD

Joseph Cullen, MD, FACS

This clinical trial is designed to determine the maximum tolerated dose of niraparib when combined with dostarlimab and hypofractionated radiation for locally advanced rectal cancer. Once this is determined, this dose will be tested to identify what impact it has on the tumor as well as patient reported outcome measures.

Standard of care therapy for resectable locally advanced rectal cancer includes pelvic radiation (short or long course), chemotherapy, and (if indicated) surgery.

In this study, participants will:

* Take niraparib by mouth once daily for up to 12 weeks.
* Receive radiation therapy once daily for five days (Monday through Friday).
* Receive intravenous (IV) dostarlimab once every three weeks for up to 12 weeks.
* Provide feedback about how they feel and their quality of life. This is done through short surveys as well as discussing with the study team.
* Undergo a sigmoidoscopy (i.e. scope of the tumor) and biopsy about halfway through treatment
* Provide tumor tissue and blood samples for analysis

A Safety Study Adding Niraparib and Dostarlimab to Radiation Therapy for Rectal Cancers

A Phase 1b/2 Trial of Preoperative Niraparib, Dostarlimab, and Hypofractionated Radiotherapy for the Treatment of Locally-advanced Rectal Cancers.

Data will be released publicly as per participant consent and IRB approval. Individual researchers should contact the research team for data sharing.

The recommended dose will be determined by incidence of dose limiting toxicities.

Clinical evaluation of the tumor by both flexible sigmoidoscopy and pelvic MRI

Time from treatment day 1 to death from any cause

Time (measured in days) to documented disease progression in imaging as described by the RECIST criteria.

Time (measured in days) to documented disease progression outside of the pelvis or death from any cause.

Time (measured in days) to disease progression within the pelvis or death from any cause.

Time (measured in days) to receipt of permanent ostomy or death from any cause.

Objective response rate, measured using the standardized RECIST criteria, is a reflection of complete tumor response and partial tumor response. The

Absence of viable tumor in the primary tumor bed and all regional nodes in patients recommended to undergo surgical resection regardless of response to neoadjuvant therapy.

Organ perservation defined as day 1 therapy to receipt of rectal resection for any reason

GlaxoSmithKline

Joseph Caster, Ph.D., M.D.

Assistant Professor

Symptoms and General Pathology

Neoplasm Metastasis

Total Mesorectal Excision plus Lateral Lymph Node Dissection for low rectal cancer with regional lymph node metastasis.

Total Mesorectal Excision After Neoadjuvant Chemo-radiotherapy for low rectal cancer with regional lymph node metastasis.

patients in TME+LLND group receive Lateral Lymph Node Dissection (LLND) after Total Mesorectal Excision(TME)

TME+LLND

patients in TME+nCRT group receive Neoadjuvant Chemo-radiotherapy (nCRT) before Total Mesorectal Excision(TME)

TME+nCRT

Yanxin Luo

Shaoyong Peng

Yanxin Luo, PhD,MD

Shaoyong Peng, MD

Treatment for Low rectal cancer, especially in patients with regional lymph node metastasis are quite different between Japanese guideline (JSCCR) and western countries' guideline (NCCN, ESMO). While Japanese scholars advocate total mesorectal excision (TME) plus lateral lymph node dissection (LLND), European and American scholars advocate TME alone after Neoadjuvant Chemo-radiotherapy (nCRT), without the need of LLND. Accordingly, this clinical trial is designed to directly compare the efficacy and safety of these two treatment strategies for low rectal cancer with regional lymph node metastasis. It will provide high-level clinical evidence for the treatment of low rectal cancer with suspected local lymph node metastasis

There are significant differences between Japanese guidelines (JSCCR) and Western guidelines (NCCN, ESMO) in the treatment of low rectal cancer, especially in patients with regional lymph node metastasis. Japanese scholars advocated total meso rectal resection (TME) + Lateral lymph node dissection (LLND), However, European and American scholars advocate that only TME is used after new adjuvant chemo-radiation (nCRT), without LLND. Therefore, the purpose of this clinical trial was to directly compare the efficacy and safety of these two treatment strategies for low rectal cancer with regional lymph node metastasis. This will provide a high level of clinical evidence for the treatment of low rectal cancer with suspected local lymph node metastasis

Total Mesorectal Excision(TME) With Lateral Lymph Node Dissection Versus TME After Neoadjuvant Chemo-radiotherapy

Total Mesorectal Excision(TME) With Lateral Lymph Node Dissection Versus TME After Neoadjuvant Chemo-radiotherapy of Lower Rectal Cancer With Suspected Local Lymph Node Metastasis

From the date of operation until the date of complication,assessed up to 3 years

From the date of operation until the date of complication,assessed up to 3 months

The study investigate the quality of life using the WHOQOL Scale

Sixth Affiliated Hospital, Sun Yat-sen University

Micronutrients

Capecitabine

Leucovorin

Fluorouracil

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Neoadjuvant Capecitabine concomitant to external beam radiotherapy

Capecitabine Oral Product

Neoadjuvant bolus 5-Fluorouracil concomitante to external beam radiotherapy

5Fluorouracil

A randomized two-arm study comparing preoperative CRT using oral capecitabine versus bolus 5-FU/LV concomitant to external beam radiation (50.5 Gy/28 fractions) for locally advanced rectal cancer. Main outcome was clinical response assessed using MRI and endorectal US 6-8 weeks after CRT. Secondary endpoints were pathological response, adverse effects, sphyncter preservation, quality of life, OS and DFS.

Patients harbouring rectal adenocarcinoma T3-4 or N\>0 M0 within 10 cm to anal verge were randomized in two treatment arms: (1) capecitabina orally 825mg/m2 bid. 5 days a week for 5 weeks and (2) bolus intravenous 5-FU/LV 350mg/m2/20 mg/m2 D1-D5 on the first and fifth weeks, both combined to pelvic radiotherapy, total dose 50.4 Gy in 28 fractions. Clinical stage before and after CRT was determined using pelvic Magnetic Resonance Imaging (MRI), endorectal ultrasonography (ERUS) and chest, abdominal and pelvic Computer Tomography. Surgery was planned 6 to 8 weeks after CRT. Sphincter preservation was always considered when negative margins were possible. Pathological assessment included stage (TNM 7th Ed.) and Mandard's Tumor Regression Grade (TRG). QOL questionnaires QLQ-C30 and CR38 were completed by patients before and after CRT, after surgery and during follow-up.

Capecitabine Versus Bolus 5-Fu Associated to Radiotherapy as Neoadjuvant Treatment for Rectal Cancer.

Estudo Randomizado de Fase II Com Capecitabina Versus 5-Fluorouracil/Leucovorin em Bolus Associados à Radioterapia no Tratamento Neoadjuvante de câncer de Reto Localmente avançado: INCAGI004.

IPD could be shared if requested after IRB approval.

Clinical downstaging after neoadjuvant treatment

Patholgical downstaging after neoadjuvant treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Safety Study Adding Niraparib and Dostarlimab to Radiation Therapy for Rectal Cancers	NCT04926324	Rectal Neoplasm... Rectal Neoplasm...	Niraparib Dostarlimab Short course ra...	18 Years -	University of Iowa
Total Mesorectal Excision(TME) With Lateral Lymph Node Dissection Versus TME After Neoadjuvant Chemo-radiotherapy	NCT03587480	Rectal Neoplasm...	TME+LLND TME+nCRT	18 Years - 75 Years	Sixth Affiliated Hospital, Sun Yat-sen University
Capecitabine Versus Bolus 5-Fu Associated to Radiotherapy as Neoadjuvant Treatment for Rectal Cancer.	NCT03428529	Rectal Neoplasm...	Capecitabine Or... 5Fluorouracil	18 Years - 80 Years	Instituto Nacional de Cancer, Brazil
Capecitabine Versus Bolus 5-Fu Associated to Radiotherapy as Neoadjuvant Treatment for Rectal Cancer.	NCT03428529	Rectal Neoplasm...	Capecitabine Or... 5Fluorouracil	18 Years - 80 Years	Instituto Nacional de Cancer, Brazil
Capecitabine Versus Bolus 5-Fu Associated to Radiotherapy as Neoadjuvant Treatment for Rectal Cancer.	NCT03428529	Rectal Neoplasm...	Capecitabine Or... 5Fluorouracil	18 Years - 80 Years	Instituto Nacional de Cancer, Brazil

Spots Global Cancer Trial Database for rectal neoplasm malignant