Neoplasms

Symptoms and General Pathology

All Conditions

Digestive System Diseases

Neoplasm Metastasis

Disease Progression

Colorectal Neoplasms

Liver Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplastic Processes

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Oxaliplatin

Bevacizumab

Leucovorin

Fluorouracil

Levoleucovorin

Folic Acid

Liver Extracts

Panitumumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Folinic Acid

Folate

Vitamin B9

6 cycles before and 6 cycles after surgery consisting in:

Hour 0: Oxaliplatin 85 mg/m² IV 2-h infusion

Hour 0: Folinic Acid 400 mg/m² (DL form) or 200 mg/m2 (L form) IV 2-h infusion

Hour 2: 5-FU 400 mg/m² IV bolus over 2-4 minutes

Hour 2: 5-FU 2400 mg/m² given as a continuous infusion over 46h.

On day 1 of a 14 day cycle

6 cycles before and 6 cycles after surgery consisting in:

Hour 0: Oxaliplatin 85 mg/m2 2-h infusion

Hour 0: Folinic Acid 400 mg/m2 (DL form) or 200 mg/m2 (L form) 2-h infusion

Hour 2 (before 5-FU bolus): Bevacizumab 5 mg/kg IV over 90 minutes infusion\*.

Hour 3.5: 5-FU bolus 400 mg/m2 IV bolus over 2-4 minutes

Hour 3.5: 5-FU 2400 mg/m² given as a continuous infusion over 46h.

On day 1 of a 14 day cycle

Experimental: Arm B: modified FOLFOX6 + Bevacizumab and Surgery

6 cycles before and 6 cycles after surgery consisting in:

Hour - 1 (pre chemotherapy): Panitumumab 6 mg/kg IV over 60 minutes (≤ 1000 mg) or 90 minutes (\> 1000 mg) +/- 15 min. infusion\*.

Hour 0: Oxaliplatin 85 mg/m² IV 2-h infusion

Hour 0: Folinic Acid 400 mg/m² (DL form) or 200 mg/m2 (L form) IV 2-h infusion

Hour 2: 5-FU 400 mg/m² IV bolus over 2-4 minutes

Hour 2: 5-FU 2400 mg/m² given as a continuous infusion over 46h.

On day 1 of a 14 day cycle

FOLFOX6

Surgery

Bernard Nordlinger, Pr.

Stephane Benoist, Pr.

Patients presenting with multiple innumerable liver metastases will probably never come to resection, however, for all others, including patients with numerous multiple metastases or large metastases,resection should be considered after limited chemotherapy.

There is consensus for a backbone chemotherapy consisting of fluoropyrimidine + oxaliplatin. FOLFOX was used in the previous EORTC study and is again recommended.

The addition of targeted agents to standard chemotherapy in the perioperative strategy for mCRC might increase the ORR and R0 resectability, without significant increase in toxicity, therefore translating to a better outcome.

It was therefore decided to design an open label, randomized, multi-center, 3-arm late phase II study.

Arm A: (standard) mFOLFOX6 + Surgery Arm B: (experimental) mFOLFOX6 + Bevacizumab + Surgery Arm C: (experimental) mFOLFOX6 + Panitumumab + Surgery

Efficacy of FOLFOX Alone, FOLFOX Plus Bevacizumab and FOLFOX Plus Panitumumab in Patients With Resectable Liver Metastases

Randomized Phase II Trial Evaluating the Efficacy of FOLFOX Alone, FOLFOX Plus Bevacizumab and FOLFOX Plus Panitumumab as Perioperative Treatment in Patients With Resectable Liver Metastases From Wild Type KRAS/NRAS Colorectal Cancer

Increase in progression free survival rate at 1 year in each experimental arm (mFOLFOX6 + bevacizumab or panitumumab) compared to mFOLFOX6 alone arm.

Increase in major pathological response rate between mFOLFOX6 alone arm and each experimental arm.

Compare the percentage of patients with total resection with these three treatments.

Overall survival is defined as the time interval between the date of randomization and the date of death. Patients who are still alive when last traced will be censored at the date of last follow-up.

All adverse events will be recorded; the investigator will assess whether those events are drug related (reasonable possibility, no reasonable possibility) and this assessment will be recorded in the database for all adverse events.

Amgen

Roche Pharma AG

European Organisation for Research and Treatment of Cancer - EORTC

Rare Diseases

Carcinoma

Stomach Neoplasms

Stomach Diseases

Stomach Cancer

Docetaxel

Spartalizumab

Standard FLOT regimen

* Docetaxel 50 mg/m² IV infusion on D1
* Oxaliplatine 85 mg/m² IV infusion on D1
* Leucovorin 200 mg/m² IV infusion on D1
* Fluorouracile 2600 mg/m² 24 h IV infusion on D1

with Spartalizumab PDR001 Patients will received the fixed dose of 400 mg per IV infusion on D1 every four weeks (q4w) for 2 pre-operative cycles (8 weeks) and 2 post-operative cycles (8 weeks)

perioperative treatment

Multicenter, open-label, non randomized, phase 2 trial in resectable gastric or gastroesophageal junction adenocarcinoma: Perioperative Treatment by Spartalizumab (PDR001) in Combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT)

Perioperative Treatment in Resectable Gastric Cancer With Spartalizumab (PDR001) in Combination With Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel (FLOT)

Perioperative Treatment in Resectable Gastric Cancer With Spartalizumab (PDR001) in Combination With Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel (FLOT): A Phase II Study (GASPAR)

Proportion of patients with pCR (pathologic complete response) in the primary tumour defined as: no tumour residue found in the tissue collected during the surgery evaluated by the pathologist

Disease-free survival (DFS) defined as time between inclusion and first disease progression

Overall survival (OS) defined as the time between inclusion and death whatever cause;

Proportion of patients with margin-free resection (R0), defined as a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed

Type, grade and number of Adverse Events as Assessed by CTCAE v5.0

National Cancer Institute, France

Centre Francois Baclesse

Colonic Neoplasms

Anti-Infective Agents

Herbal and Botanical

Anti-Bacterial Agents

Antibiotics, Antitubercular

Cola

early recovery program with no preoperative mechanical bowel preparation, early diet initiation, and prevention of postoperative ileus after elective laparoscopic colon cancer surgery

Traditional, conventional perioperative treatment

Enhanced recovery program day-1: no mechanical bowel preparation, intake permit until 6 hrs before operation day0: operation, postoperative fluid therapy, antibiotics day1: liquid diet, early ambulation, removal of foley catheterization day2-3: soft diet day 4-5: discharge

Enhanced recovery program

Gyu-Seog Choi, MD

An enhanced recovery program has been developed to provide for colon cancer patients faster and more personalized postoperative treatment. Most of the previous studies have showed that the efficacy of the enhanced recovery program on both subjective and objective physical recovery of patients. However, such studies are rarely conducted in South Korea. The purpose of this study is to evaluate the feasibility and efficacy of a postoperative enhanced recovery program in patients who underwent laparoscopic colon cancer surgery at a tertiary hospital in Korea.

Enhanced Recovery Program After Laparoscopic Colon Cancer Surgery

Implementation of an Enhanced Recovery Program After Laparoscopic Colon Cancer Surgery

Duration of hospital stay from the date of operation to the date when a patient meets the following "discharge criteria".

Discharge criteria:

* Tolerance of consecutive 3 soft diet
* Recovery of bowel function (without PONV)
* No necessity of intravenous analgesics
* Stable vital sign (afebrile)

Body weight, body mass index, body composition, before and after surgery

Kyungpook National University Hospital

Director, Head of colorectal cancer center, Principal Investigator, Professor

Aflibercept

6 cycles before and 6 cycles after surgery consisting in:

Hour 0: Aflibercept 4 mg/kg intravenous infusion 1-h

Hour 1: Oxaliplatin 85 mg/m2 2-h infusion

Hour 1: Folinic Acid 400 mg/m2 (DL form) or 200 mg/m2 (L form) 2-h infusion

Hour 3: 5-FU bolus 400 mg/m2 IV bolus over 2-4 minutes

Hour 3: 5-FU 2400 mg/m² given as a continuous infusion over 46h.

Day 1 of a 14 day cycle

Aflibercept should be given in all cycles, except cycle 6 of pre-operative treatment.

Modified FOLFOX6

Patients presenting with multiple innumerable liver metastases will probably never come to resection, however, for all others, including patients with numerous multiple metastases or large metastases, resection should be considered after limited chemotherapy.

There is consensus for a backbone chemotherapy consisting of fluoropyrimidine + oxaliplatin. FOLFOX was used in the previous EORTC study and is again recommended.

The addition of targeted agents to standard chemotherapy in the perioperative strategy for mCRC might increase the ORR and R0 resectability, without significant increase in toxicity, therefore translating to a better outcome.

BOS2 (EORTC 40091) was designed to test this hypothesis in patients with a KRAS wold-type profile.

It was decided in parallel to design an open label, randomized, multi-center, 2-arm phase II-III study this time aimed at enrolling KRAS mutated patients.

Arm A: (standard) mFOLFOX6 + Surgery Arm B: (experimental) mFOLFOX6 + Aflibercept + Surgery

Efficacy of FOLFOX Versus FOLFOX Plus Aflibercept in K-ras Mutant Patients With Resectable Liver Metastases

BOS3: Randomized Phase II/III Trial Evaluating the Efficacy of FOLFOX Alone Versus FOLFOX Plus Aflibercept in K-ras Mutant as Perioperative Treatment in Patients With Resectable Liver Metastases From Colorectal Cancer.

Increase in progression free survival rate at 1 year in the experimental arm (mFOLFOX6 + aflibercept) compared to mFOLFOX6 alone arm.

Sanofi

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Capecitabine

Clinically diagnosed stage T2-3/N+M0,orT4aN+M0 according to CT/MRI scan, and resectable

Patients will be given the perioperative chemotherapy as below once recruited:

Capecitabine ：500 mg tablets（Roche） Oxaliplatin：50mg/10ml（according to daily practice in each center）

Schedule of Oxaliplatin plus capecitabine (XELOX) will be as follow:

Capecitabine 1000 mg/m2 ，orally taken 30 minutes after meal, bid ， d 1\~14 every 3 weeks(treatment for 2 weeks and rest 1 week) Oxaliplatin：130mg/m2， iv infusion over 2h，d1,every 3 weeks

XELOX

Tianshu Liu, Doctor

Tianshu Liu, doctor

Yiyi yu, Master

1. Target population:locally advanced gastric adenocarcinoma (LAGC, cT2\~3/N+M0,or cT4aN+M0);no previous chemo or radio therapy.
2. Primary objective:Response rate of XELOX in the neoadjuvant setting of LAGC.

   Secondary objectives:
   * The progression free survival (PFS) in the perioperative treatment of locally advanced gastric adenocarcinoma (cT3/N+M0,or cT4aN+M0);
   * percentage of pathological response ; percentage of grade 3 or 4 adverse events as safety profile of perioperative treatments;
   * D2 resection -rate after neoadjuvant chemotherapy of XELOX;
   * Overall survival;
   * QOL during the whole period of treatment.
3. Trial design:This is a multicenter, single arm, open-label, phase II study to evaluate the efficacy and safety of Oxaliplatin plus capecitabine(XELOX) in the perioperative treatment of locally advanced gastric adenocarcinoma in combination with D2 resection.
4. Treatment plan:Patients will be given the perioperative chemotherapy as below once recruited:Schedule of Oxaliplatin plus capecitabine (XELOX) will be as follow: Capecitabine 1000 mg/m2 ，bid,d 1\~14 every 3 weeks(treatment for 2 weeks and rest 1 week)Oxaliplatin：130mg/m2， iv infusion over 2h，d1,every 3 weeks.
5. Number of subjects:50 patients.Number of centers 5 sites, which have the high volume of gastric operations in China, more than 500 per year.

1. Disease specific inclusion criteria:

   * Histologically documented gastricadenocarcinoma with Lauren classification Clinically diagnosed stage T2-3/N+M0,orT4aN+M0 according to CT/MRI scan, and resectable
   * Measurable disease is required
   * Karnofsky score 80%.
   * Physical condition and adequate organ function to ensure the success of abdominal surgery.
   * Life expectancy ≥12 weeks.
   * Adequate hematological function: Neutrophil count ≥ 1.5 × 109/L, Platelets ≥ 100 × 109/L and Hemoglobin ≥8g/dL .Adequate liver function: Total bilirubin ≤ 1.5 × upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) \< 2.5 × ULN in the absence of liver metastases, or \< 5 × ULN in case of liver metastases. ALP ≤ 2.5 × upper limit of normal (ULN); ALB ≥30g/L.

   Adequate renal function: Serum creatinine ≤ 1.25 x ULN, and creatinine clearance ≥ 60 ml/min.
   * Female subjects should not be pregnant or breast-feeding.
   * No serious concomitant disease that will threaten the survival of patients to less than 5 years.
2. General inclusion criteria:

   * Male or female. Age ≥ 18 years and ≤75 years
   * Written (signed) informed consent.
   * Able to comply with study and follow-up procedures.
   * Good compliance with the treatment plan。
   * Consent to provide tissue sample。

Oxaliplatin Plus Capecitabine in the Perioperative Treatment of Locally Advanced Gastric Adenocarcinoma

A Multicenter, Single Arm, Open-label Trial of Oxaliplatin Plus Capecitabine (XELOX) in the Perioperative Treatment of Locally Advanced Gastric Adenocarcinoma

the response rate evaluation will be based on tumor assessment with follow-up, including chest and upper-abdominal During preoperative treatment period, CT scan will be performed every 6 -8 weeks (2 cycles after)., brain MRI and bone scan (ECT) will be performed if any suspected symptoms occur.

progression by the evidence of CT/MRI scan at each evaluation at neoadjuvant period or follow-up time after surgery；During preoperative treatment period, CT scan will be performed every 6 -8 weeks (2 cycles after).After syrgery, CT scan will be planned every 6 months, brain MRI and bone scan (ECT) will be performed if any suspected symptoms occur.

After surgery，the pathological response will be measured by the pathologist for every Operation patient.

Adverse events and clinical laboratory tests will be recorded by CTCAE (version 4.0) during the whole treatment period.

During the OS follow-up, out-patient clinic and telephone visit will be done every 3 months for the first two years, and every 6 months after two years.

These assessment will be evaluated at every evaluation.

Ruijin Hospital

RenJi Hospital

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Fudan University

Shanghai Zhongshan Hospital

Director of Medical oncology derpartment

Antibodies

Irinotecan

Immunoglobulins

FOLFOX:

Oxaliplatin at a dose of 85 mg/m2 iv over two hours (day 1) I-LV at a dose of 200 mg/m2 iv over two hours (day 1) 5-FU at a dose of 3200 mg/m2 iv over 48 hours (day 1-3)

Duration of treatment:

Treatment will be administered for 12 cycles (6 months) postoperatively starting 6 weeks after surgery.

Therapy will be administered in a biweekly schedule. First preoperative cycle will be administered with 75% of dosage for FOLFOXIRI, if no diarrhea ≥ grade 3 occurs, following cycles should be administered in full dosage.

FOLFOXIRI + bevacizumab:

bevacizumab at a dose of 5 mg/kg iv over 30 to 90 min (day 1) irinotecan at a dose of 165 mg/m2 iv over two hours (day 1) oxaliplatin at a dose of 85 mg/m2 iv over two hours (day 1) I-LV at a dose of 200 mg/m2 iv over two hours (day 1) 5-FU at a dose of 3200 mg/m2 iv over 48 hours (day 1-3)

Duration of treatment:

Treatment will be administered for 6 cycles (3 months) preoperatively (last cycle without bevacizumab), after 6 weeks followed by liver surgery, after further 6 weeks followed by 6 cycles (3 months) postoperatively.

Bevacizumab at a dose of 5 mg/kg iv over 30 to 90 min (day 1) + FOLFOXIRI in a biweekly schedule, 6 cycles preoperatively, 6 cycles postoperatively

Hans J. Schlitt, Prof. MD

Hans-Joachim Schmoll, Prof. MD

This randomized, controlled, multicenter, non-comparative phase II trial compares an intensified perioperative treatment of patients with resectable synchronous or metachronous colorectal liver metastases to primary surgery and adjuvant systemic chemotherapy.

Recurrence rates after R0-resection of colorectal liver metastases are still very high (about 60-70 %). Therefore, multidisciplinary treatment of these patients is frequently used in order to achieve a beneficial impact regarding progression-free and overall survival. The point in time of treatment, pre- and/or postoperative, is still a matter of debate. In the EORTC 40983 trial, perioperative chemotherapy with 5-Fluorouracil and oxaliplatin (FOLFOX-Regimen) displayed a non-significant benefit in 3 year disease free survival in the intent to treat population (HR 0.79, 95% CI 0.62 to 1.02) (Nordlinger, Sorbye et al. 2008). The combined analysis of two adjuvant trials, with a (non-contemporary) 5-FU Bolus regimen, showed a non-significant prolongation of median disease free survival (DFS) from 18.8 to 27.9 months (p=0.058) and OS from 47.3 to 62.2 months (p=0.095) (Mitry, Fields et al. 2008). However, postoperative treatment with 6 months of FOLFOX is often used in daily practise. Thus, further investigation is urgently warranted.

This phase II trial evaluates two strategies with intensified perioperative or postoperative treatment regimens. Current studies established the role of the FOLFOXIRI regimen in the metastatic setting (Falcone, Ricci et al. 2007). A further intensification of a three drug regimen with bevacizumab seem to be feasible yielding response rates up to 84% and a disease control rate up to 100% (Falcone 2008; Bruera, Santomaggio et al. 2010; Masi, Loupakis et al. 2010). Regarding the efficacy, evaluation of FOLFOXIRI and bevacizumab in preoperative treatment for resectable CLM seems to be promising. Postoperative treatment with FOLFOX for 6 months was chosen for arm A.

Perioperative Treatment of Resectable Liver Metastases

Perioperative FOLFOXIRI and Bevacizumab Compared With Postoperative FOLFOX in Patients With Resectable Liver Metastases From Colorectal Cancer (PERIMAX). A Randomized, Multidisciplinary DGAV(CAO-V/CALGP)/AIO Phase II Trial

Failure will be defined as no R0 resection, local or distant recurrence or death from any cause.

University of Halle Medical Faculty

University of Regensburg

Principal Investigator

Antimetabolites

Topoisomerase I Inhibitors

Enzyme Inhibitors

capecitabine, oxaliplatin, irinotecan and bevacizumab

Filippo de Braud, MD

Capecitabine, oxaliplatin, irinotecan and bevacizumab as perioperative strategy of borderline and/or high risk resectable colorectal cancer liver metastases

Previous studies demonstrated a significant association between tumor regression grade of hepatic colorectal metastases (TRG1: complete pathological response; TRG2: major pathological response; TRG3: partial pathological response; versus TRG4-5 no pathological response) and outcome in terms of survival after neoadjuvant treatment. In particular, retrospective data showed an association between oxaliplatin-based chemotherapy and improvement of grade and percentage of tumor regression; moreover, the addition of Bevacizumab seems to improve TRG over chemotherapy alone, conferring also a protection against liver damage due to chemotherapy-induced sinusoidal obstruction syndrome.

This is the rationale that induced us to carry out an evaluation and feasibility assessment of a perioperative approach with COI-B regimen in patients affected by high risk or borderline resectable colorectal liver metastases, with or without previous resection of primary tumor.

PERIOPERATIVE TREATMENT WITH COI-B (CAPECITABINE, OXALIPLATIN, IRINOTECAN AND BEVACIZUMAB) OF HIGH RISK OR BORDERLINE RESECTABLE COLORECTAL CANCER LIVER METASTASES

Primary:

- To evaluate the activity of the regimen with regards to major/complete pathological response. Major/complete pathological response is measured by pathologist in terms of tumor regression grade (TRG) as described by Rubbia-Brandt L, Annals of Oncology 2007 (percentage of vial residual cells 0-10%).

- Response rate according to RECIST vers. 1.1 criteria

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy of FOLFOX Alone, FOLFOX Plus Bevacizumab and FOLFOX Plus Panitumumab in Patients With Resectable Liver Metastases	NCT01508000	Colorectal Canc... Liver Metastase... KRAS Wild Type ...	FOLFOX6 Bevacizumab Panitumumab Surgery	18 Years - 75 Years	European Organisation for Research and Treatment of Cancer - EORTC
Perioperative Treatment in Resectable Gastric Cancer With Spartalizumab (PDR001) in Combination With Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel (FLOT)	NCT04736485	Gastric Cancer ... Resectable Carc...	perioperative t...	18 Years -	Centre Francois Baclesse
Enhanced Recovery Program After Laparoscopic Colon Cancer Surgery	NCT02399631	Colon Cancer	Enhanced recove...	20 Years - 80 Years	Kyungpook National University Hospital
Efficacy of FOLFOX Versus FOLFOX Plus Aflibercept in K-ras Mutant Patients With Resectable Liver Metastases	NCT01646554	Colorectal Canc... Liver Metastase... KRAS Mutated Co...	Modified FOLFOX... Aflibercept Surgery	18 Years - 75 Years	European Organisation for Research and Treatment of Cancer - EORTC
Oxaliplatin Plus Capecitabine in the Perioperative Treatment of Locally Advanced Gastric Adenocarcinoma	NCT01880632	Gastric Adenoca...	XELOX	18 Years - 75 Years	Shanghai Zhongshan Hospital
Perioperative Treatment of Resectable Liver Metastases	NCT01540435	Colon Cancer Li...	Bevacizumab	18 Years - 75 Years	University of Regensburg
PERIOPERATIVE TREATMENT WITH COI-B (CAPECITABINE, OXALIPLATIN, IRINOTECAN AND BEVACIZUMAB) OF HIGH RISK OR BORDERLINE RESECTABLE COLORECTAL CANCER LIVER METASTASES	NCT02086656	Colorectal Canc...	capecitabine, o...	18 Years -	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Spots Global Cancer Trial Database for perioperative treatment