Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Rectal Neoplasms

Gastrointestinal Neoplasms

Intestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Oxaliplatin

Irinotecan

Capecitabine

The standard-of-care group receives short-course radiation therapy (5 × 5 Gy) followed by six cycles of CAPOX (capecitabine 1000 mg/m2 orally twice daily on days 1-14, oxaliplatin 130 mg/m2 intravenously on day 1, q3wks).

SCRT

Six cycles of CAPOX capecitabine 1000 mg/m2 orally twice daily on days 1-14, oxaliplatin 130 mg/m2 intravenously on day 1, every 3 weeks

CAPOX

Six cycles of CAPOX capecitabine 800 mg/m2 orally twice daily on days 1-14, oxaliplatin 130 mg/m2 intravenously on day 1 and irinotecan 200 mg/m2 intravenously on day 1, every 3 weeks)

CAPOXIRI

Yoshinori Kagawa, MD., PhD

Jun Watanabe, MD., PhD

Takayuki Yoshino, Dr.

Eiji Oki, Dr.

Masahiko Sugiyama, Dr.

Tetsuya Kusumoto, Dr.

Nobuhisa Matsuhashi, Dr.

Miura Takuya, Dr.

Hideki Ohdan, Dr.

Naoki Izawa, Dr.

Keiji Hirata, Dr.

Goro Nakayama, Dr.

Mitsuru Yokota, Dr.

Junichiro Kawamura, Dr.

Takesh Kato, Dr.

Yoshinori Kagawa, Dr.

Mamoru Uemura, Dr.

Takeshi Naito, Dr.

Ichiro Takemasa, Dr.

Takashi Akiyoshi, Dr.

Takeshi Okabayashi, Dr.

Yukihide Kanemitsu, Dr.

Takeshi Yamada, Dr.

Kazushige Kawai, Dr.

Manabu Shiozawa, Dr.

Atsushi Ishibe, Dr.

Jun Watanabe, Dr.

Hirokazu Suwa, Dr.

This trial is a multicenter randomized Phase III study to verify the superiority of short-course preoperative radiation (SCRT) and CAPOXIRI over SCRT and CAPOX as preoperative treatments for locally advanced rectal cancer.

Total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC) has the promise, which means non-operative management (NOM) enable more patients (pts) with a complete clinical response (cCR) or near-complete clinical responses (nCR) after TNT to avoid subsequent radical surgery, with potentially maintaining anorectal function and quality of life (QoL). Recently, PRODIGE-23 trial demonstrated that triplet regimen (Irinotecan, oxaliplatin and fluoropyrimidine) before preoperative chemoradiotherapy (CRT) significantly improved outcomes compared with CRT. However, there has been no prospective study comparing consolidation triplet with doublet regimens following short course radiotherapy (SCRT). The aim of this randomized phase III trial is to test superiority of consolidation irinotecan, capecitabine and oxaliplatin (CAPOXIRI) vs. capecitabine and oxaliplatin (CAPOX) following SCRT as TNT in pts with LARC.

Pts in both groups will be re-staged after completing TNT before radical surgery according to the Memorial Sloan Kettering Regression Schema; pts with incomplete response (iCR) will undergo total mesorectal excision (TME), cCR pts will receive NOM, and nCR pts will undergo TME or NOM by a physician discretion under the recommendation of blind assessment by the designated NOM central committee. Pts will be followed by CT, MRI, colonoscopy and liquid biopsy every 4 months for 2 years, and every 6 months thereafter up to 5 years.

To detect a decrease in 3-year cumulative probability of organ preservation-adapted Disease free survival (DFS) from 75.0% to 81.7%, corresponding to a target hazard ratio of 0·70, a total of 608 pts (196 events) would achieve 70% power at a two-sided α significance level of 0.05.

standard arm: 5x5Gy -\> 12 wks CAPOX -\> restating -\> surgery or non-operative management experimental arm: 5x5Gy -\> 12 wks CAPOXIRI -\> restating -\> surgery or non-operative management

Total Neoadjuvant Therapy of SCRT+CAPOX vs SCRT+CAPOXIRI for Locally Advanced Rectal Cancer (ENSEMBLE)

A Multicenter Randomized Phase III Study of Short-term Radiotherapy Plus CAPOX and Short-term Radiotherapy Plus CAPOXIRI as Preoperative Treatment for Locally Advanced Rectal Cancer

A part of the omics analysis data obtained in the analysis of this study may be disclosed through public databases such as the "Human Database" operated by National Bioscience Database Center (NBDC) in Japan Science and Technology Agency (JST). When registering data, re-anonymization will be provided to strengthen the protections of personal information. At the time of NBDC registration, we will comply with the "NBDC Guidelines for Human Data Sharing" and "NBDC Security Guidelines for Human Data(for Data Providers)" .

Analysis using liquid biopsy will be performed to identify biomarkers that predict therapeutic effects by performing blood genome profiling.

Using multiple algorithms, in addition to colonoscopy and pelvic MRI images at each point, clinicopathological features, various biomarkers, and QOL will be utilized to estimate the optimal treatment method for individual research subjects

The investigators use the definition of organ-preservation adopted DFS proposed in the international consensus statement for preoperative treatment (75). It is defined as the period from the date of allocation to the earliest of the following events.

1. Surgery difficult due to local progression or study subject unfit for surgery
2. R2 resection of primary tumor ( not including Circumferential resection margin (CRM) positive )
3. Local recurrence after R0/1 resection of primary tumor
4. Local regrowth for which Salvage surgery is not possible during NOM
5. Appearance of distant metastases
6. Occurrence of second primary colorectal cancer
7. Development of second primary other cancers
8. Death (treatment-related death, death from the same cancer, death from a different type of cancer, non-cancer-related death)

The investigators will use the Memorial Sloan Kettering Regression Schema, which is the cCR standard for TNT clinical trials conducted mainly in the United States.

For judgment, a gastrointestinal endoscopist, a pathological diagnostician, and a gastrointestinal surgeon discuss and comprehensively judge.

The proportion of the number of research subjects for whom NOM was selected at the time of re-evaluation to the analysis population as the numerator. Study subjects who died of any cause before the re-evaluation decision date will be treated as "no complete resection" and included in the denominator but not the numerator.

The recurrence site is classified into local recurrence, distant recurrence, and unknown, and is defined as "recurrence type". Select multiple categories if recurrence is observed at multiple sites at the time of the first recurrence.

The period from the date of allocation to the date of determination of distant metastasis or the date of death due to any cause, whichever is earlier. An event that corresponds to any of the following is defined as a DMFS event.

1. Distant metastasis
2. Death (treatment-related death, death from the same cancer, death from a different type of cancer, non-cancer-related death)

The period from the date of allocation to the date of local recurrence or the date of death due to any cause, whichever is earlier. An event that corresponds to any of the following is defined as an LRFS event.

1. Local recurrence
2. Death (treatment-related death, death from the same cancer, death from a different type of cancer, non-cancer-related death)

From the date of allocation to the date of death due to any cause. Based on " Protocol 8.2.17 Confirmation of outcome and confirmation of recurrence after protocol treatment", the confirmation of survival should be recorded in the medical record, etc.). Patients with no follow-up will be censored on the date of final confirmation of survival.

As the earliest of the date of definitive TME at reevaluation, the date of TME at local recurrence (excluding local excision), and the date of death from any cause. An event corresponding to any of the following is defined as a TME free survival event.

1. TME when electing surgery at reevaluation
2. TME with salvageable local regrowth in NOM
3. Death (treatment-related death, death from the same cancer, death from a different type of cancer, non-cancer-related death)

With the date of assignment as the starting date, the date on which radical TME was performed at reevaluation, the date on which TME was performed at the time of local recurrence (excluding local excision), and Organ-preservation adopted DFS defined in Protocol 12.2.1. The period up to the earliest of the event occurrence dates. An event that corresponds to any of the following is defined as an event of TME-free disease-free survival.

1. TME when electing surgery at reevaluation
2. TME with salvageable local regrowth in NOM
3. Organ preservation - adopted DFS defined in Protocol 12.2.1. is not applicable because TME is implemented)

The analysis population who completed protocol treatment.

RDI is calculated for each case, each cycle, and each drug (capecitabine, oxaliplatin, irinotecan) in the analysis target population. The actual number of cycle days refers to the number of days from the start of the corresponding course to the start date of the next course, but the actual number of cycle days in the final course is the number of days from the start date of the last course to the actual day of administration of capecitabine + 6 days. defined as RDI (%) = (Actual Dose/Prescribed Dose) x (21/Actual Cycle Days) x 100

Using a quality of life questionnaire to assess the following items: LARS score, EORTC QLQ-C30, SF-36

Incidence of preoperative treatment-related adverse events determined by CTCAE ver5.0

Pathological response evaluation will be performed on the surgical specimens of the subgroup that underwent surgical resection in the protocol treatment.

Histopathological evaluation of antitumor efficacy is based on the American Joint Committee on Cancer (AJCC) evaluation method. pCR is defined as no viable tumor cells not only in the primary tumor but also in the regional lymph nodes (ypT0N0).

Percentage of study subjects judged to be pCR in the analysis population.

Proportion of study participants who underwent a complete resection (confirmed postoperative pathological R0) in the analyzed population in the surgical resection subgroup in protocol treatment. Study subjects who died of any cause prior to the date of surgery were treated as "no complete resection" and included in the denominator but not the numerator.

In the subgroup that underwent surgical resection in protocol treatment, the period from the date of surgery to the date of local recurrence or the date of death from any cause, whichever comes first.

For early (within 30 days) and late (31-90 days) postoperative adverse events after the end of surgical therapy, the worst grade according to the Clavien-Dindo classification v2.0 is calculated.

Proportion of study subjects with local regrowth in the analysis population in the subgroups that underwent NOM.

In the subgroup that underwent NOM, the date of NOM determination is the starting date, and the period from the date of local regrowth to the date of death from any cause, whichever is earlier.

In the NOM subgroup, the proportion of study subjects with local regrowth and salvage surgery in the analysis population.

In the NOM subgroup, the time to the date of salvage surgery at the time of local regrowth or the date of death from any cause, whichever is earliest.

In the subgroup that underwent NOM, among the population to be analyzed, in cases where local regrowth was performed and salvage surgery was performed, early (within 30 days) and late (31-90 days) postoperative adverse events after the end of surgical therapy , find the worst grade by Clavien-Dindo classification v2.0.

Proportion of study subjects with local regrowth and radical salvage surgery in the analyzed population in the NOM subgroup.

Japan Agency for Medical Research and Development

National Cancer Center Hospital East

MD., PhD Head of Department of Gastroenterology and Gastrointestinal Oncology

Colonic Diseases

Micronutrients

Bone Density Conservation Agents

Hematinics

Vitamins

Bevacizumab

Leucovorin

Fluorouracil

Levoleucovorin

Calcium

Calcium, Dietary

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Hormones

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folinic Acid

Folate

Vitamin B9

Induction therapy is followed by the maintenance therapy.

\[Induction treatment: CAPOXIRI+BEV\] Administered for 6 cycles (a maximum of 8 cycles). BEV: 7.5mg/kg (d.i.v.) oxaliplatin (OX): 100/130 mg/sq.m (d.i.v.) irinotecan (IRI):150/180/200mg/sq.m (d.i.v.) CAP 1,600 mg/sq.m /day (p.o. day1-15) Administered every 3 weeks. OX/IRI dose is applied according to the progress of Step 1.

\[Maintenance treatment: 5-fluorouracil (FU)/Levofolinate calcium (LV)+BEV or CAP+BEV\] The following 5-FU/LV+BEV therapy will be repeated in 2-week cycles, or the following CAP+BEV therapy will be repeated in 3-week cycles (Physician's choice). No change in treatment regimen will be permitted after the selection of maintenance therapy (5-FU/LV+BEV or CAP+ BEV).

5-FU/LV+BEV: BEV:5mg/kg (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks.

CAP+BEV: BEV: 7.5mg/kg (d.i.v.) CAP 1,600 mg/sq.m /day (po. day1-15) Administered every 3 weeks.

Induction therapy is followed by the maintenance therapy.

\[Induction treatment: FOLFOXIRI+BEV\] Administered for 8 cycles (a maximum of 12 cycles). BEV: 5mg/kg (d.i.v.) OX: 85 mg/sq.m (d.i.v.) IRI:165mg/sq.m (d.i.v.) LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks.

\[Maintenance treatment: 5-FU/LV+BEV or CAP+BEV\] The following 5-FU/LV+BEV therapy will be repeated in 2-week cycles, or the following CAP+BEV therapy will be repeated in 3-week cycles (Physician's choice). No change in treatment regimen will be permitted after the selection of maintenance therapy (5-FU/LV+BEV or CAP+ BEV).

5-FU/LV+BEV: BEV:5mg/kg (d.i.v.) LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks.

CAP+BEV: BEV: 7.5mg/kg (d.i.v.) CAP 1,600 mg/sq.m /day (po. Day1-15) Administered every 3 weeks.

Induction therapy is followed by the maintenance therapy.

\[Induction treatment: CAPOXIRI+BEV\] Administered for 6 cycles (a maximum of 8 cycles). BEV: 7.5mg/kg (d.i.v.) OX: 100/130 mg/sq.m (d.i.v.) IRI:150/180/200mg/sq.m (d.i.v.) CAP 1,600 mg/sq.m /day (p.o. day1-15) Administered every 3 weeks. Regarding to OX/IRI dose, RD will be confirmed at Step 1.

\[Maintenance treatment: 5-FU/LV+BEV or CAP+BEV\] The following 5-FU/LV+BEV therapy will be repeated in 2-week cycles, or the following CAP+BEV therapy will be repeated in 3-week cycles (Physician's choice). No change in treatment regimen will be permitted after the selection of maintenance therapy (5-FU/LV+BEV or CAP+ BEV).

5-FU/LV+BEV: BEV:5mg/kg (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks.

CAP+BEV: BEV: 7.5mg/kg (d.i.v.) CAP 1,600 mg/sq.m /day (po. day1-15) Administered every 3 weeks.

5-fluorouracil

Leucovorin calcium

Irinotecan hydrochloride

Tsunehiko Tateuchi

Takeshi Kato, M.D.,Ph.D.

Akihito Tsuji, M.D.,Ph.D.

Takayuki Yoshino, M.D.,Ph.D.

Eiji Oki, M.D.,Ph.D.

Masahito Kotaka, M.D.,Ph.D.

Yoshito Komatsu, M.D.,Ph.D.

Hiroya Taniguchi, M.D.,Ph.D.

Kei Muro, M.D.

Kentaro Yamazaki, M.D.,Ph.D.

Takeharu Yamanaka, Ph.D.

Hironaga Satake, M.D.,Ph.D.

Hideaki Bando, M.D.,Ph.D.

Takeshi Kato, M.D., Ph.D.

Akihito Tsuji, M.D., Ph.D.

The objective is to compare the efficacy and safety of CAPOXIRI+BEV therapy versus FOLFOXIRI+BEV therapy as first-line therapy in patients with metastatic colorectal cancer (mCRC).

QUATTRO-II is an open-label, multicenter, randomised, phase II study to investigate the efficacy and safety of CAPOXIRI+BEV versus FOLFOXIRI+BEV in 1st line mCRC.

This study is composed two steps because of confirming of recommended dose (RD) for CAPOXIRI+BEV regimen.

1. Dose finding step (Step1): CAPOXIRI+BEV doses findings were planned by 3+3 cohort design, register up to maximum of 12 cases.
2. Randomised step (Step2): After confirmation of RD regarding CAPOXIRI+BEV, we will move to Step2 to compare the efficacy and safety between FOLFOXIRI+BEV and CAPOXIRI+BEV, register up to 65 cases.

CAPOXIRI+Bevacizumab vs. FOLFOXIRI+Bevacizumab for mCRC

Quadruplet 1st Line Treatment of CAPOXIRI Plus Bevacizumab Versus FOLFOXIRI Plus Bevacizumab for mCRC, Multicenter Randomised Phase II Study (QUATTRO-II)

PFS by investigator-reported measurements according to CT image. PFS was calculated from the day of treatment start to the first observation of progression disease (PD) or death from any cause.PD was defined as Overall Response by RECIST criteria v1.1 according to CT image.

Adverse events were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. All adverse events was collected in duration from starting treatment to whichever shorter "after 30 days from withdrawal treatment" or "later treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Total Neoadjuvant Therapy of SCRT+CAPOX vs SCRT+CAPOXIRI for Locally Advanced Rectal Cancer (ENSEMBLE)	NCT05646511	Locally Advance...	SCRT CAPOX CAPOXIRI	18 Years -	National Cancer Center Hospital East
CAPOXIRI+Bevacizumab vs. FOLFOXIRI+Bevacizumab for mCRC	NCT04097444	Metastatic Colo...	Bevacizumab 5-fluorouracil Leucovorin calc... Irinotecan hydr... Oxaliplatin Capecitabine	20 Years -	Chugai Pharmaceutical
CAPOXIRI+Bevacizumab vs. FOLFOXIRI+Bevacizumab for mCRC	NCT04097444	Metastatic Colo...	Bevacizumab 5-fluorouracil Leucovorin calc... Irinotecan hydr... Oxaliplatin Capecitabine	20 Years -	Chugai Pharmaceutical
CAPOXIRI+Bevacizumab vs. FOLFOXIRI+Bevacizumab for mCRC	NCT04097444	Metastatic Colo...	Bevacizumab 5-fluorouracil Leucovorin calc... Irinotecan hydr... Oxaliplatin Capecitabine	20 Years -	Chugai Pharmaceutical

Spots Global Cancer Trial Database for capoxiri

Every month we try and update this database with for capoxiri cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for capoxiri

Every month we try and update this database with for capoxiri cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for capoxiri cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.