Antineoplastic Agents

All Drugs and Chemicals

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

1. Name: Sorafenib
2. Dosage form: 200 mg / Tablet
3. Dosing schedule: 200 mg bid, po, everyday, since Day 8 of Cycle 1

1. Name:S-1
2. Dosage form: 20 mg or 25 mg / Capsule
3. Dosing schedule: 20-40 mg/m2 bid,po, 14 days on \& 7 days off

Li-Tzong Chen, M.D., Ph.D.

Primary Objective:

1. To define the recommended dose for phase II study of S-1 combined with sorafenib
2. To evaluate the dose-limiting toxicities of the combination therapy

Secondary Objectives:

1. To characterize the pharmacokinetics (PK) of sorafenib and S-1 in the combination therapy
2. To investigate the impact of genetic polymorphisms of metabolic genes on the PK of sorafenib and S-1, respectively, as well as on the toxicity profile of the combination.
3. To determine the changes of biomarkers between pre- and post-treatments.

Sorafenib Plus S-1 in Advanced Solid Tumors

An Open-Label Phase I Dose-Escalation Study of Sorafenib Plus S-1 in Advanced Solid Tumors

National Cheng-Kung University Hospital

National Health Research Institutes, Taiwan

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Urinary Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Paclitaxel

Gemcitabine

Doxorubicin

Liposomal doxorubicin

Methotrexate

Albumin-Bound Paclitaxel

Avelumab

Cisplatin

Vinblastine

Antineoplastic Agents, Immunological

Methotrexate, vinblastine, doxorubicin and cisplatin (DD-MVAC) given in combination with Avelumab.

DD-MVAC consists of Methotrexate 30 mg/m2 iv day 1, Vinblastine 3 mg/m2 iv day 2, Cisplatin 70 mg/m2 iv day 2 and Doxorubicin 30 mg/m2 iv day 2. Each cycle is given every 2 weeks for a maximum of 4 administrations Chemotherapy is associated with Avelumab 10 mg/kg, 1-hour intravenous (iv) infusion, given on day 2 every 2 weeks.

Cystectomy will be performed 3 to 6 weeks after last administration of chemotherapy

Cisplatin, gemcitabine (CG) consists of Gemcitabine 1000 mg/m2 iv in day 1 and day 8 and Cisplatin 70 mg/m2 iv in day 1. Each cycle is given every 3 weeks for a maximum of 4 administrations.

Chemotherapy is associated with Avelumab 10 mg/kg, 1-hour intravenous (iv) infusion, given on day 1 every 2 weeks Cystectomy will be performed 3 to 6 weeks after last administration of chemotherapy

Paclitaxel, gemcitabine (PG) consists of Paclitaxel 80 mg/m2 iv in day 1 and day 15 and Gemcitabine 1000 mg/m2 iv in day 1 and day 15. Each cycle is repeated every 3 weeks for a maximum of 4 administrations.

Chemotherapy is associated with Avelumab 10 mg/kg, 1-hour intravenous (iv) infusion, given on day 1 every 2 weeks Cystectomy will be performed 3 to 6 weeks after last administration of chemotherapy

Avelumab will be administered at a dose of 10 milligram per kilogram (mg/kg) 1-hour intravenous (iv) infusion once every 2 weeks. Dose reductions are not allowed.

Avelumab will be given alone for 4 administrations. Cystectomy will be performed 2 weeks after the last administration of avelumab

Chemotherapy with or without avelumab followed by surgery

Cystectomy 3 to 6 weeks after last administration of chemotherapy

cystectomy

DD-MVAC

Open-label, interventional, multi-centre, randomized phase II study. Cancer studied is non-metastatic muscle invasive bladder cancer (MIBC).

Avelumab administered every 2 weeks is used as neoadjuvant therapy in subjects with urothelial muscle invasive bladder cancers in combination with standard chemotherapy or alone.

Open-label, interventional, multi-centre, randomized phase II study. Cancer studied is non-metastatic muscle invasive bladder cancer (MIBC) Patients (male or female) will receive avelumab every 2 weeks in combination with standard chemotherapy or alone. There are 2 cohorts of patients.

Cohort with patients cisplatin-ineligible will receive either avelumab alone or in combination with paclitaxel-gemcitabine chemotherapy.

Cohort with patients cisplatin-eligible will receive either methotrexate, vinblastine, doxorubicine and cisplatin in combination with avelumab or cisplatin, gemcitabine in combination with avelumab.

The estimated number of subjects to screen is 183 patients for an estimated number of 166 patients enrolled for 150 evaluable patients:

26 patients in the paclitaxel, gemcitabine in combination with avelumab arm (cisplatin-ineligible patients) 26 patients in avelumab alone arm (cisplatin-ineligible patients) 49 patients in cisplatin gemcitabine + avelumab arm (cisplatin-eligible patients) 49 patients in methotrexate, vinblastine, doxorubicine and cisplatin + avelumab arm (cisplatin-eligible patients)

AVELUMAB:

Avelumab will be administered at a dose of 10 milligram per kilogram (mg/kg) 1-hour intravenous (iv) infusion once every 2 weeks. Dose reductions are not allowed.

Depending on the treatment arm, Avelumab will be given associated with chemotherapy or alone for a maximum of 4 administrations.

DD-MVAC:

DD-MVAC consists of Methotrexate 30 mg/m2 iv day 1, Vinblastine 3 mg/m2 iv day 2, Cisplatin 70 mg/m2 iv day 2 and Doxorubicin 30 mg/m2 iv day 2. Each cycle is given every 2 weeks for a maximum of 4 administrations. Pegfilgrastim 6 mg subcutaneous (SQ) 24-48 hours after completion of chemotherapy will be given.

Chemotherapy is associated with Avelumab 10 mg/kg iv given on day 2 every 2 weeks.

CG:

CG consists of Gemcitabine 1000 mg/m2 iv in day 1 and day 8 and Cisplatin 70 mg/m2 iv in day 1. Each cycle is given every 3 weeks for a maximum of 4 administrations. Pegfilgrastim 6 mg subcutaneous (SQ) 24-48 hours after completion of chemotherapy will be given.

Chemotherapy is associated with Avelumab 10 mg/kg iv given on day 1 every 2 weeks.

PG:

PG consists of Paclitaxel 80 mg/m2 iv in day 1 and day 15 and Gemcitabine 1000 mg/m2 iv in day 1 and day 15. Each cycle is repeated every 4 weeks for a maximum of 4 administrations.

Chemotherapy is associated with Avelumab 10 mg/kg i.v. given every on day 1 every 2 weeks.

For patients receiving neoadjuvant chemotherapy treatment, the surgery (cystectomy or nephroureterectomy associated to lymphadenectomy) will be performed within 3-6 weeks after the last administration of neoadjuvant chemotherapy treatment.

For patients receiving avelumab alone, the surgery will be performed 2 weeks (+7 days) after the last administration of avelumab.

Any delay in surgery (\> 6 weeks after the last chemotherapy administration or \>3 weeks after the last administration of avelumab alone) for any reason, needs to be discussed with the PI/Sponsor.

For all patients, neoadjuvant treatment will be stopped if there is evidence of progression of disease (by RECIST 1.1 or investigator's decision) or unacceptable toxicity according to the investigator. In this situation, the investigator will decide if it is needed to proceed directly with the surgery.

The end of study will be declared when all the following criteria will have been met:

* The study ends after last visit of the last patient remaining in the study.
* The trial is mature for the analysis of the endpoints as defined in the protocol, if the trial reaches its endpoints.
* The database has been fully cleaned and frozen for all analyses.

Open-label, randomized study. 2 cohorts possible depending on cisplatin-eligibility. Afterwards randomization between 2 arms into the cohort.

Avelumab as Neoadjuvant Therapy in Subjects With Urothelial Muscle Invasive Bladder Cancers (AURA Trial)

Avelumab as Neoadjuvant Therapy in Subjects With Urothelial Muscle Invasive Bladder Cancers

- Outcome measure: Pathological complete response is defined as the absence of invasive carcinoma (ypT0/Tis) disease and the absence of microscopic lymph node metastases (ypN0) on the final surgical specimen.

Outcome measure: Pathologic response is defined as the absence of muscle invasive carcinoma (\<ypT2N0 disease) on the final surgical specimen.

Outcome measure: adverse events reported during the study according to NCI CTCAE v4.03

Outcome measure: invasive disease-free survival (iDFS) rate. iDFS period is defined as a time between the surgery (or last treatment dose if no surgery) and the date of diagnosis of local or distant recurrence, or secondary primary malignancy

overall survival (OS) rate. Overall survival is defined as a time between the surgery (or last treatment dose if no surgery) and the day of death (due to any causes) or day of last news

Merck KGaA, Darmstadt, Germany

Jules Bordet Institute

Symptoms and General Pathology

Digestive System Diseases

Fistula

Pancreatic Fistula

Pathological Conditions, Anatomical

Digestive System Fistula

Gastrointestinal Diseases

Pancreatic Diseases

Standard PD with regional lymphadenectomy was performed. PG was done between pancreatic stump and posterior surface of the stomach with 2 layer interrupted anastomosis,and duct to mucosa.

Isolated Roux PJ group, reconstruction was begun using the transected jejunum and ,which was anastomosed in end to side fashion. A separate Roux loop was performed for HJ, by dividing the jejunum about 40 cm beyond the pancreatic anastomosis and GJ was done in this loop (30 cm caudally from HJ). The PJ loop was anastomosed to the main loop (20 cm caudal to GJ).

Pancreaticogastrostomy group

Isolated Roux PJ group

Ayman El Nakeeb, MD

Pancreaticoduodenectomy (PD)is the treatment of choice for patients with periampullary tumour (benign or malignant). In the recent years, the mortality rate of PD has decreased to 5% in many centers. However, pancreatic fistula (POPF) still occurs in 5 % to 40% of patients after PD. The hypothesis that isolated Roux loop PJ with isolated pancreatic drainage decrease the incidence of PF and severity with preservation of pancreatic function.

So the investigators compare isolated Roux Loop Pancreaticojejunostomy (PJ) Versus Pancreaticogastrostomy (PG) as regards incidence of POPF, severity of POPF and functional outcome.

The hypothesis that isolated Roux loop PJ decrease the incidence of PF and severity with preservation of pancreatic function (exocrine and endocrine functions).

Preoperative evaluation included abdominal CT, liver function, tumor marker CEA, CA19-9, preoperative ERCP were optional in selected cases (patients with high bilirubin with high enzymes. Patients with distant metastasis or locally advanced were excluded.

Informed consent was obtained from all patients entered in the study Randomization: enrolled patients were randomized intraoperatively after PD resection to either isolated Roux PJ with isolated pancreatic drainage group or PG group by closed envelope which withdrawn by the nurse.

Operative technique. Standard PD with regional lymphadenectomy was performed. PG was done between pancreatic stump and posterior surface of the stomach with 2 layer interrupted anastomosis,and duct to mucosa.

Isolated Roux PJ group, reconstruction was begun using the transected jejunum and, which was anastomosed in end to side fashion. A separate Roux loop was performed for HJ, by dividing the jejunum about 40 cm beyond the pancreatic anastomosis and GJ was done in this loop (30 cm caudally from HJ). The PJ loop was anastomosed to the main loop (20 cm caudal to GJ).

One intrabdominal drains in morrison space. Intraoperative data and postoperative data were collected. Pancreatic function assessment.

The primary outcome was assessment the incidence of POPF after isolated Roux PJ and PG. The secondary outcomes were intraoperative blood loss, drain amount,day to resume oral intake hospital stay, operative duration, pancreatic function, postoperative complications delayed gastric emptying,

Isolated Roux Loop Pancreaticojejunostomy Versus Pancreaticogastrostomy After Pancreaticoduodenectomy

Postoperative pancreatic fistula was defined as drainage of \> 50 ml/d of amylase rich fluid( 3 folds elevation above upper limit of normal in serum)

Delayed gastric emptying, bile leakage, bleeding PG, bleeding GJ

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Sorafenib Plus S-1 in Advanced Solid Tumors	NCT01128998	Advanced Solid ...	Sorafenib S-1	20 Years - 75 Years	National Health Research Institutes, Taiwan
Avelumab as Neoadjuvant Therapy in Subjects With Urothelial Muscle Invasive Bladder Cancers (AURA Trial)	NCT03674424	Non-metastatic ...	Avelumab cystectomy CG DD-MVAC PG	18 Years -	Jules Bordet Institute
Isolated Roux Loop Pancreaticojejunostomy Versus Pancreaticogastrostomy After Pancreaticoduodenectomy	NCT01859806	Pancreatic Fist...	Pancreaticogast... Isolated Roux P...	-	Mansoura University

Spots Global Cancer Trial Database for pg

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

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