Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Traditional open procedure for patient with locally advanced gastric cancer

Minimum invasive procedure (laparoscopic) for patient with locally advanced gastric cancer

Laparoscopic procedures

Open Surgery

Igor Khathov, MD, PhD

Roman Izrailov, MD, PhD

Michail Lando, MD, PhD

Boris Pomortsev, MD

Michail Prostov

Pavel Kononets

Andrey Ryabov, MD, PhD

Vladimir Lyadov, MD, PhD

Andrey Pavlenko, MD, PhD

Victor Kashchenko, MD, PhD

Alexey Karachun, MD, PhD

Sergey Baydo, MD, PhD

Michail Byachov, MD, PhD

Pavel Kononets, MD, PhD

Igor Khatkov, MD, PhD

Kirill Schostka, MD, PhD

Nowadays, the proportion of patients with locally advanced gastric cancer is estimated up to 90 percent of all gastric cancer cases in Russian Federation. Surgical procedure with D2 Lymphadenectomy is the main option for treatment. Conventional open approach is still the current standard for advanced gastric cancer. Laparoscopic procedures for gastric cancer as minimally invasive surgery has gained popularity for the treatment of early gastric cancer in East Asia. Several studies indicated that laparoscopic procedures both total and subtotal gastrectomy with D2 lymphadenectomy is a technically feasible and safe procedure by experienced surgeons in high-volume specialized hospitals. However, lack of solid evidence on the oncologic efficacy.

Starting clinical trials for evaluate safety of oncology laparoscopic subtotal gastrectomy for locally advanced gastric cancer. Aim of this trial is show safety, feasibility and oncologic efficacy of Laparoscopic radical surgical procedures both total and subtotal gastrectomy for treatment gastric cancer.

A Comparison Laparoscopic With Open Gastric Cancer Surgery for Locally Advanced Gastric Cancer

Prospective Multicenter Study on Laparoscopic Gastric Cancer Surgery Compared With Open Surgery for Locally Advanced Gastric Cancer

"Major" Surgical morbidity is defined as the complication grade on III-V Clavien-Dindo Classification which occurs with-in postoperative 21 days, extension of hospitalization and re-hospitalization. It is necessary to evaluate the complication and if it occurs during the hospitalization, it is required to record complication name, date of on-set (postoperatively), grade on Clavien-Dindo Classification and treatment for complication.

In terms of locally advanced gastric cancer, to evaluate the progression-free survival rate in laparoscopic gastrectomy with D2 lymph node dissection at postoperative 3 years compared with open procedures

In terms of locally advanced gastric cancer, to evaluate the overall survival rate in laparoscopic gastrectomy with D2 lymph node dissection at postoperative 3 years compared with open procedures

In terms of locally advanced gastric cancer, to evaluate the overall survival rate in laparoscopic gastrectomy with D2 lymph node dissection at postoperative 5 years compared with open procedures

It is defined as the death within postoperative 90 days regardless of postoperative reason.

Minimally-invasive surgery is associated with less peri-operative blood loss. Blood loss will be measured in milliliters and average blood loss will be compared to the conventional 'open' group.

Time to first ambulation, flatus, liquid diet, soft diet, and duration of hospital stay are used to assess the postoperative recovery course The amount of abdominal drainage and blood transfusion are also recorded

Pain scores based on a visual analog scale the day of surgery and the subsequent 3 days postoperative 1 days, 2 days, 3 days

Both the European Organization for Research and Treatment of Cancer (EORTC) C30 and STO22 are analyzed with quality of life

Surgical morbidity is defined as the events which occurs with-in postoperative 21 days - 36 months after surgery. It is necessary to evaluate the complication, it is required to record complication name, date of on-set. Long complications are included: hernia, bleeding, bowel obstruction etc.

The extent of lymph node dissection in treatment of gastric cancer is considered a prognostic marker for postoperative survival and disease-free survival. Before implementation of a new surgical technique, it is imperative that this technique is non-inferior with regard to the extent of lymph node dissection. Measures will include the number of resected lymph nodes and the number of resected lymph node stations.

Moscow Clinical Scientific Center

Cholangiocarcinoma

Klatskin Tumor

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

Anti-Inflammatory Agents

All Drugs and Chemicals

ABC294640

Mark L Levitt, MD, PhD

Vered Katz Ben-Yair, MSc

This is an expanded access program (EAP) for eligible participants who do not qualify for participation in, or who are otherwise unable to access, the ongoing clinical trial ABC-108. This program is designed to provide access to ABC294640 (Yeliva ®) for treatment of cholangiocarcinoma (CCA) prior to approval by the local regulatory agency. Availability will depend on territory eligibility. Participating sites will be added as they apply for and are approved for the EAP. An oncologist must decide whether the potential benefit outweighs the risk of receiving an investigational therapy based on the individual patient's medical history and program eligibility criteria.

Expanded Access for the Treatment of Advanced Cholangiocarcinoma With ABC294640 (Yeliva ®)

Expanded Access to ABC-108, A Phase IIA Study of ABC294640 in the Treatment of Patients With Advanced,Unresectable Intra-hepatic, Perihilar and Extra-Hepatic Cholangiocarcinoma

RedHill Biopharma Limited

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Anti-Infective Agents

Antineoplastic Agents

Hormones

Sirolimus

Anastrozole

Aromatase Inhibitors

Temsirolimus

MTOR Inhibitors

Antineoplastic Agents, Hormonal

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Following inclusion, patients will be randomized (2:1) to receive Arm A : AZD2014 + anastrozole Arm B : anastrozole alone

Mode of Action Selective and specific mTOR kinase inhibitor targeting both mTORC1 and mTORC2 complexes.

Route of Administration Oral

Dosage regimen 125mg BID with intermittent schedule (2 days of treatment followed by 5 days off (500mg/week))

Duration of treatment Until the patient experiences unacceptable toxicity, disease progression and/or treatment is discontinued per patient or investigator request.

AZD2014

Therapeutic Class Aromatase inhibitor

Mode of Action Potent and highly selective non-steroidal aromatase inhibitor.

Route of Administration Oral

Dosage regimen

1 mg tablet once a day

Duration of treatment Patients may continue treatment with anastrozole until the patient experiences unacceptable toxicity, disease progression and/or treatment is discontinued per patient or investigator request.

Pierre-Etienne HEUDEL, MD

The investigators hypothesize that the dual inhibition of mTORC1/mTORC2 by AZD2014 combined with inhibition of aromatase enzyme by anastrozole will act synergistically and may be an interesting therapeutic option for endometrial cancer with a manageable toxicity profile.

The investigators proposal is to conduct a multicenter, 2-step, randomized, Phase I/II trial to evaluate the safety and efficacy of a combination treatment associating anastrozole to AZD2014 in advanced endometrial cancer patients.

The study is divided in 2 steps :

* A safety run-in phase aiming to evaluate the safety of the proposed combination AZD2014 + anastrozole (Arm A) versus anastrozole alone (Arm B). No dose escalation is scheduled (doses are based on maximum tolerated dose (MTD) defined for AZD2014 and the summary of product characteristics (SPC) of anastrozole). However, dose de-escalation for AZD2014 will be applied in case of toxicity.
* A two-stage randomized Phase II part aiming to evaluate the clinical benefit of the AZD2014 + anastrozole (Arm A) combination therapy versus anastrozole (Arm B).

TREATMENT PLAN :

Following randomisation patients will receive Arm A : AZD2014 plus anastrozole or Arm B: anastrozole alone AZD2014 will be administered with an intermittent schedule i.e. 125 mg bis in die (BID) intermittent with 2 days on followed by 5 days off per week for a total weekly dose of 500 mg/week (250mg D1 and D2, 5 days off) Anastrozole will be administered at the standard dose defined in the SPC i.e. 1mg/d, per os, continuously.

Both treatment will be administered until progressive disease (PD), unacceptable toxicity or willingness to stop.

STATISTICS :

A total of 72 patients will be randomized in the study.

Safety run-in Phase on the first 9 patients randomized - As no dose escalation will be performed, the safety will be evaluated following the treatment and 8-week follow-up of the first 6 patients by the experimental association AZD2014+anastrozole (experimental arm). By similarity to a classic 3+3 design, based on binomial probabilities, there is a 90% probability of observing one or more patients with a toxicity event, if that event occurs in at least 32% of the target population. Assuming a 2:1 randomization ratio, a total of 9 patients (Arm A - Experimental: 6 patients, Arm B - Control: 3 patients) will be enrolled in this safety run-in phase and will be included in the evaluation of Phase II part.

Phase II The sample size calculation was based on a Simon optimal two-stage design, with a minimum success (8-week non progression) rate considered of interest p1=60% and an uninteresting rate p0=40%. Assuming a type I error alpha of 0.05 and 80% power, 46 evaluable patients are needed in the experimental arm to reject the null hypothesis H0: p≤p0 versus the alternative hypothesis H1: p ≥ p1 in a unilateral situation (16 patients in Stage I and 30 additional patients in Stage II).

With a 2:1 randomization and based on the assumption that 5% of the patients may be non-evaluable, a total of 72 patients will be included in the study : 48 patients in Arm A - experimental and 24 patients in Arm B - control).

DATA ENTRY, DATA MANAGEMENT AND STUDY MONITORING All the data concerning the patients will be recorded in the electronic case report form (eCRF) throughout the study. serious adverse event (SAE) reporting will be also paper-based by e-mail and/or Fax.

The sponsor will perform the study monitoring and will help the investigators to conduct the study in compliance with the clinical trial protocol, Good Clinical Practices (GCP) and local law requirements.

Hormone Receptor Positive endometrIal Carcinoma Treated by Dual mTORC1/mTORC2 Inhibitor and Anastrozole (VICTORIA)

A Multicentric, Randomized, Non Comparative, Open-label Phase I/II Evaluating AZD2014 (Dual Mammalian Target of Rapamycin Complex 1/2 (mTORC1/mTORC2) Inhibitor) in Combination With Anastrozole Versus Anastrozole Alone in the Treatment of Metastatic Hormone Receptor-positive Endometrial Adenocarcinoma

Severe toxicities defined as

* Any grade ≥ 4 treatment related toxicity
* Any grade≥ 3 treatment related toxicity lasting more than 7 days

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Comparison Laparoscopic With Open Gastric Cancer Surgery for Locally Advanced Gastric Cancer	NCT02748551	Gastric Cancer	Laparoscopic pr... Open Surgery	18 Years - 82 Years	Moscow Clinical Scientific Center
Expanded Access for the Treatment of Advanced Cholangiocarcinoma With ABC294640 (Yeliva ®)	NCT03414489	Cholangiocarcin... Cholangiocarcin... Cholangiocarcin... Cholangiocarcin... Cholangiocarcin...	ABC294640	18 Years -	RedHill Biopharma Limited
Hormone Receptor Positive endometrIal Carcinoma Treated by Dual mTORC1/mTORC2 Inhibitor and Anastrozole (VICTORIA)	NCT02730923	Endometrial Car... Metastatic Carc... Hormone Recepto...	AZD2014 Anastrozole	18 Years -	Centre Leon Berard
Expanded Access for the Treatment of Advanced Cholangiocarcinoma With ABC294640 (Yeliva ®)	NCT03414489	Cholangiocarcin... Cholangiocarcin... Cholangiocarcin... Cholangiocarcin... Cholangiocarcin...	ABC294640	18 Years -	RedHill Biopharma Limited

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