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

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Anti-Infective Agents

Fibrinolytic Agents

Anticoagulants

Antipyretics

Antirheumatic Agents

Analgesics

Platelet Aggregation Inhibitors

Bone Density Conservation Agents

Antibodies

Dexamethasone

Anti-Bacterial Agents

Bendamustine Hydrochloride

Heparin

Aspirin

Calcium

Lenalidomide

Dexamethasone acetate

Antibiotics, Antitubercular

Warfarin

Immunoglobulins

Omeprazole

Calcium heparin

Heparin, Low-Molecular-Weight

Tinzaparin

Dalteparin

Acyclovir

Calcium, Dietary

Immunoglobulins, Intravenous

Fluconazole

Trimethoprim, Sulfamethoxazole Drug Combination

Histamine H2 Antagonists

Proton Pump Inhibitors

Ranitidine

Ranitidine bismuth citrate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Treatment with Bendamustine in combination with Lenalidomide and Dexamethasone will be administered on an outpatient basis. Each treatment cycle will be 28 days dosed according to the Dose Escalation Schema.

Bendamustine is given intravenously (into a vein or IV infusion) on days 1 and 2 of each cycle. Each bendamustine infusion will take 60 minutes

Bendamustine

Lenalidomide is taken orally (by mouth) in the morning on days 1 through 21 of each cycle.

Dexamethasone is taken orally (by mouth) on days 1, 8, 15, and 22 of each cycle.

All patients will receive enteric coated aspirin, 325 mg, QD while on study. If patient is unable to tolerate aspirin, patient should receive other types of anti-coagulation like Coumadin or low molecular weight heparin.

All patients will receive prophylaxis with either an H-2 blocker or proton pump inhibitor (PPI) while on study medications. Suggested medications included ranitidine 150 mg PC BID or omeprazole 20 mg PO QD or equivalent.

Prophylaxis

PCP antibiotic prophylaxis with a Bactrim will be recommended. In case of history of zoster or fungal infection a prophylaxis with Acyclovir or Diflucan should be also considered.

Antibiotic

Vital signs (heart rate, breathing rate, blood pressure, and temperature) will be measured, and Blood tests to check CBC, Calcium, Electrolytes, serum, creatinine, and BUN. This follow up will take place at the Hillman Cancer Center, or whichever cancer center in which the subject is treated.

Biweekly Follow Up

At the beginning of each treatment cycle subjects will undergo a Physical exam, a Performance status check, Recording of any new symptoms or side effects and any new medications, Blood tests (including blood chemistry, organ function and indicators of disease), Urine test, and pregnancy test (if applicable).

Cyclical Follow Up

Every other cycle subjects' disease will be restaged. This will be accomplished by their treatment physician. Re-staging procedures includes a regular office visit, x-ray, and a bone marrow biopsy. Subjects will spend approximately 4 hours at the Hillman Cancer Center or the UPMC Cancer Center location where they are being treated for this re-staging.

Restaging

After subjects stop receiving the study drugs, they will be followed every 3 months for the first two years, every 6 months for years 2-5, and annually thereafter. The following procedures, which are considered routine for their cancer care, will be done as part of this follow-up:

* Physical exam
* Performance status (check of ability to perform daily functions)
* Recording of any new symptoms and any new medications being taken
* Blood tests to check blood counts (numbers of red and white blood cells and platelets), blood chemistry (to check organ function), and indicators of disease (immunoglobulins)
* Urine test (24hr urine)
* Women who are able to have children will have a pregnancy test (4 weeks after their last dose of lenalidomide).
* A check of the status of disease (includes bone marrow biopsy, skeletal survey, and blood and urine tests). Bone marrow biopsy will be done at the end of treatment, if subjects have a complete response, and their disease gets worse.

Post-Treatment Follow Up

Robert L Redner, M.D.

The purpose of this study is to see if the combination of bendamustine, lenalidomide and dexamethasone will help people with multiple myeloma that has returned after standard treatment or has been resistant to other treatments.

Bendamustine in Combination With Lenalidomide and Dexamethasone in Refractory or Relapsed Multiple Myeloma

Phase I Study of Bendamustine in Combination With Lenalidomide (CC-5013) and Dexamethasone in Patients With Refractory or Relapsed Multiple Myeloma

Cephalon

Robert Redner, MD

Professor, Division of Hematology/Oncology, Department of Medicine

Pharmaceutical Solutions

All patients will be treated according to standard practice of the concerning hospital.

Patients in group I are patients that will be stratified for direct surgery (TME) or a short-course of radiotherapy (5x5 Gy) followed by immediate TME.

Group I will undergo only a staging MRI, including gadofosveset-enhanced MRI.

All patients will be treated according to standard practice of the concerning hospital.

Patients in group II are patients that will be stratified for a long course of chemoradiotherapy.

Group II will undergo a staging MRI, a re-staging MRI and a optional sigmoidoscopy as part of restaging. MRI includes diffusion-weighted imaging and gadofosveset-enhanced MRI.

Gadofosveset will be used as a lymph-node specific MRI contrast agent and will be administered by manual injection as a single intravenous bolus during MRI.

GADOFOSVESET TRISODIUM 244 Mg in 1 mL INTRAVENOUS INJECTION, SOLUTION [Ablavar]

Regina Beets-Tan, Prof. MD.

Geerard Beets, Ass Prof. MD

Doenja Lambregts, MD

Monique Maas, MD

The purpose of this study is to determine the clinical value of the novel MRI-techniques DWI and gadofosveset-enhanced MRI for the management of rectal cancer patients.

Rectal cancer is a common form of cancer, and the treatment stratification depends on tumour and nodal stage as determined on MRI. Unfortunately, the information provided by standard T2-weighted MRI is not sufficient to accurately assess nodal involvement and tumour response after neo-adjuvant chemoradiotherapy. Additional functional information is required for reliable (re)staging. Diffusion-weighted imaging and gadofosveset-enhanced MRI are two new imaging techniques that have all shown great potential in rectal cancer staging. In order to provide definite evidence there is a need for a multicenter study with a large patient population.

Diagnostic Value of Novel MR Imaging Techniques for the Primary Staging and Restaging of Rectal Cancer

Techniques under investigation are diffusion-weighted imaging for tumour response assessment and gadofosveset-enhanced MRI for nodal assessment, compared to standard T2-weighted MRI.

Detection of the differences between expert vs non-expert readers and general vs referral centres concerning diffusion-weighted imaging and gadofosveset-enhanced MRI.

Dutch Cancer Society

Maastricht University Medical Center

Behaviors and Mental Disorders

Quality of Life

The population will consist of patients, aged 18 years or older, with locally advanced rectal cancer who after chemoradiation have a clinical complete response (ycT0N0) or very good response (ycT1-2N0).

1. European Organisation for Research and Treatment of Cancer (EORTC) QLQ-30 questionnaire, version 3.0, Global Quality of Life Score
2. Short Form (36) health survey
3. EORTC CR38
4. Vaizey score
5. Low Anterior Resection Syndrome (LARS) score
6. International Index of Erectile Function for men
7. International Prostate Symptom Score for men
8. Female Sexual Function Index for women

Questionnaires for the evaluation of Quality of Life

Manometry is a tool to measure the anal sphincter function. Patients do not need any bowel preparation before this procedure. During the examination a catheter tip will be positioned in the rectum above the sphincter and a small balloon will be inflated. This balloon is connected to a device that registers the measurements. Patients will receive instructions; e.g. squeeze, push, and cough. The procedure takes approximately 10 minutes and is not experienced as painful. Several parameters will be measured: the mean basal pressure, the maximum squeeze pressure, first sensation, first urge to defecate and the maximum tolerable volume. The manometric measurement will take place on the same day as the endoscopy and MRI (standard follow-up).

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
Bendamustine in Combination With Lenalidomide and Dexamethasone in Refractory or Relapsed Multiple Myeloma	NCT01042704	Myeloma	Bendamustine Lenalidomide Dexamethasone Aspirin Prophylaxis Antibiotic Biweekly Follow... Cyclical Follow... Restaging Post-Treatment ...	18 Years -	University of Pittsburgh
Diagnostic Value of Novel MR Imaging Techniques for the Primary Staging and Restaging of Rectal Cancer	NCT01721785	Rectal Neoplasm... Magnetic Resona... Neoplasms Stagi...	GADOFOSVESET TR...	18 Years -	Maastricht University Medical Center
Functional Outcome of Organ Preservation After Neo-adjuvant Chemo Radiation for Rectal Cancer	NCT02278653	Rectal Neoplasm...	Questionnaires ... Manometry	18 Years -	Maastricht University Medical Center
Diagnostic Value of Novel MR Imaging Techniques for the Primary Staging and Restaging of Rectal Cancer	NCT01721785	Rectal Neoplasm... Magnetic Resona... Neoplasms Stagi...	GADOFOSVESET TR...	18 Years -	Maastricht University Medical Center

Spots Global Cancer Trial Database for restaging

Every month we try and update this database with for restaging 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 restaging

Every month we try and update this database with for restaging 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 restaging 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.