Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Tubulin Modulators

Antimitotic Agents

Dose escalation stage: oral administration, Volitinib 600mg/800 QD + docetaxel 75mg/m2.

If the dose of docetaxel 75mg/m2 is not tolerable, docetaxel dose will be reduced to 60mg/m2 while keep volitinib at 600mg QD as the initial dose. Volitinib dose escalation will be re-started and end at the dose of 800mg QD.

Dose expansion Stage:Volitinib with docetaxel. Use the prefer dose from escalation stage

Volitinib

Jin Li, Prof.

The purpose of this study is to evaluate the safety and tolerability of volitinib in combination with docetaxel in patients with locally advanced or metastatic gastric cancer and to determine the Maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of volitinib in combination with docetaxel.

This is a phase Ib, open-label study.

There are two stages to this study: a dose-escalation stage and a dose-expansion stage. Approximately 40-50 patients will be enrolled in this two-stage study, about 12-18 patients in the dose-escalation stage and approximately 30 patients in the dose-expansion stage.

Dose escalation stage

Gastric cancer patients who failed the first line therapy (no matter the cMet status) who meet the eligibility criteria will be enrolled into this stage.

Cohort 1: Volitinib 600mg QD + docetaxel 75mg/m2 Cohort 2: Volitinib 800mg QD+ docetaxel 75mg/m2 The conventional 3+3 design (3 patients per dose cohort, with the potential to add additional 3 patients to the same cohort to further evaluate toxicity) will be applied for dose escalation and MTD or RP2D determination. Each treatment cycle will be composed of 3 weeks or 21 days. Dose escalation and entry of the next cohort will occur only after acceptable tolerance has been demonstrated throughout the entire Cycle1.

Dose expansion Stage

Additional patients will be enrolled at the MTD or RP2D to further refine the safety, tolerability, PK, and efficacy at this dose. Patients will be limited to the metastatic / locally advanced gastric cancer patients who failed the first therapy and with positive cMet test results. Patients will be divided into two treatment groups according their c-Met test results:

Group A: FISH + , IHC -/+(about 15 patients) Group B: IHC+ and FISH- (about 15 patients)

A Study of Safety and Pharmacokinetics of Volitinib With Docetaxel in Patients With Advanced Gastric Cancer

A Phase Ib, Open-label Study of Safety and Pharmacokinetics of Volitinib in Combination With Docetaxel in Patients With Advanced Gastric Cancer

* Incidence and nature of DLTs
* Incidence and severity of AE/SAEs

* Area Under Curve (AUC)
* Maximum plasma concentration (Cmax)
* Clearance (CL/F)
* Volume of distribution (Vd/F)
* Other parameters, such as accumulation ratio, elimination half-life

AstraZeneca

Hutchison Medipharma Limited

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Amino Acids

Osimertinib

Mitogens

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

osimertinib

savolitinib (300 mg oral OD or 300 mg oral BID or 600 mg oral OD)

savolitinib

placebo

AstraZeneca Clinical Study Information Center

Lecia V Sequist, MD MPH

Myung-Ju Ahn, MD

This study (the SAVANNAH study) will investigate the efficacy of osimertinib in combination with savolitinib in patients with EGFRm+ and MET+, locally advanced or metastatic NSCLC who have progressed following treatment with osimertinib

The combination of osimertinib with savolitinib in this study (the SAVANNAH study) will explore if the combination will overcome MET-amplification as a mechanism of resistance. The SAVANNAH study will investigate the efficacy of osimertinib in combination with savolitinib in patients with EGFRm+ and MET-amplified/overexpressed, locally advanced or metastatic NSCLC who have progressed following treatment with osimertinib.

Eligible patients will be those with histologically or cytologically confirmed diagnosis of EGFRm+, MET amplified/overexpressed (FISH10+ and/or IHC90+) NSCLC that is locally advanced or metastatic and is not amenable to further surgery or radiotherapy with curative intent. The disease must have progressed following treatment with first line osimertinib. Patients must have confirmation of MET-amplified/overexpressed tumour by central FISH and IHC testing (requirements summarised in the main body of the protocol and fully explained in the Central Laboratory Manual). Patients must not have received prior or current treatment with savolitinib or another MET inhibitor.

All patients confirmed as eligible will begin treatment on Day 1 with osimertinib + savolitinib combination therapy or placebo to osimertinib + savolitinib. Treatment will continue in 28 day cycles until either objective disease progression by investigator per RECIST 1.1 is assessed, unacceptable toxicity occurs, consent is withdrawn or another discontinuation criterion is met.

Under Protocol versions 1-6 the study model was single arm (open-label).

Starting protocol version 7 patients will be randomised in a double blinded manner to receive savolitinib in combination with osimertinib or savolitinib with placebo to osimertinib with crossover option upon disease progression assessed by Investigator.

Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib

A Phase II Study Assessing the Efficacy of Osimertinib in Combination With Savolitinib in Patients With EGFRm+ and MET+, Locally Advanced or Metastatic Non Small Cell Lung Cancer Who Have Progressed Following Treatment With Osimertinib.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

To assess the efficacy of savolitinib plus osimertinib and savolitinib plus placebo, respectively, on CNS metastases in patients with CNS metastases at baseline.

To assess the efficacy of savolitinib plus osimertinib and savolitinib plus placebo, respectively, on the prevention of CNS metastases in patients without CNS metastases at baseline.

To assess the impact of savolitinib in combination with osimertinib on patient reported treatment-related symptoms.

To assess patients' overall impression of severity of cancer symptoms. In patients centrally confirmed as MET positive in all patients.

To explore the impact of treatment and disease on health state utility. In patients centrally confirmed as MET positive in all patients.

To assess the predictive value of changes in circulating biomarkers on clinical efficacy endpoints.

To collect and store DNA (according to each country's local and ethical procedures) for future exploratory research into genes/genetic variation that may influence response (ie, distribution, safety, tolerability and efficacy) to study treatments and or susceptibility to disease (optional).

To collect and store tissue, plasma and serum samples for diagnostic development and exploratory analyses.

To collect and store germline DNA for exploration of the role of HLA alleles in developmental toxicity.

To determine the efficacy of savolitinib (300 mg bid) in combination with osimertinib in patients with EGFRm+ and MET amplified/overexpressed (FISH10+ and/or IHC90+), locally advanced or metastatic NSCLC who have progressed following treatment with 1L osimertinib

To determine the efficacy of savolitinib (300 mg od) in combination with osimertinib in patients with EGFRm+, MET amplified/overexpressed (FISH5+ and/or IHC50+), locally advanced or metastatic NSCLC who have progressed following osimertinib.

To determine the efficacy of savolitinib (300 mg bid) in combination with osimertinib in patients with EGFRm+ and MET amplified/overexpressed (FISH10+ and/or IHC90+), locally advanced or metastatic NSCLC who have progressed following treatment with 1L osimertinib.

To describe the difference in the efficacy of savolitinib (300 mg bid) in combination with osimertinib and savolitinib (300 mg bid) in combination with placebo in patients with EGFRm+, MET amplified/overexpressed (FISH10+ and/or IHC90+), locally advanced or metastatic NSCLC who have progressed following treatment with 1L osimertinib therapy under CSP version 7.0.

To determine the efficacy of savolitinib (300 mg od and 600 mg od, respectively) in combination with osimertinib in patients with EGFRm+, MET amplified/overexpressed (FISH10+ and/or IHC90+), locally advanced or metastatic NSCLC who have progressed following treatment with 1L osimertinib.

To determine the efficacy of savolitinib (300 mg od, 300 mg bid, and 600 mg od, respectively) in combination with osimertinib in patients with EGFRm+, MET amplified/overexpressed (FISH10+ and/or IHC90+), locally advanced or metastatic NSCLC who have progressed following treatment of ≥ 2L osimertinib.

To determine the efficacy of savolitinib (300 mg bid, and 600 mg od, respectively) in combination with osimertinib in patients with EGFRm+, MET amplified/overexpressed (FISH5+ and/or IHC50+), locally advanced or metastatic NSCLC who have progressed following osimertinib.

To determine the efficacy of savolitinib (300 mg od, 300 mg bid, and 600 mg od, respectively) in combination with osimertinib in patients with EGFRm+, MET amplified/overexpressed (FISH5+ and/or IHC50+), locally advanced or metastatic NSCLC who have progressed following osimertinib.

To determine the efficacy of (1) 300 mg od, 300 mg bid and 600 mg od of savolitinib in combination with osimertinib in patients with EGFRm+ MET amplified/ overexpressed (FISH 10+ and/or IHC90+); (2) 300 mg od, 300 mg bid and 600 mg od of savolitinib in combination with osimertinib in patients with EGFRm+ MET amplified/overexpressed (FISH5+ and/or IHC50+) (3) savolitinib 300 mg bid in combination with osimertinib and savolitinib 300 mg bid in combination with placebo, respectively, in patients with EGFRm+ MET amplified/ overexpressed (FISH10+ and/or IHC90+) following treatment with 1L osimertinib.

To assess the impact of savolitinib and osimertinib on disease related symptoms and health related quality of life (HRQoL) in this patient population.

To evaluate the pharmacokinetics of osimertinib and savolitinib in this patient population.

To determine the prevalence of ctDNA clearance after osimertinib and savolitinib treatment in this patient population.

To evaluate the safety and tolerability of savolitinib in combination with osimertinib and savolitinib in combination with placebo.

Hutchison MediPharma

There are six dose cohorts,including 100, 200, 400, 600,800 and 1000 mg/day, HMPL-504 will be administered orally to patients once daily for each dose cohort.

An alternative dosing schedule of twice every day (BID) may be investigated if pharmacokinetic studies indicate faster than anticipated clearance of Volitinib(HMPL-504).

Volitinib(HMPL-504) is a tablet in the form of 25 mg ,100mgand 200 mg,oral,once daily.

Michael Millward, MD,Ph.D

Hui Gan, MD,Ph.D

Jason Lickliter, MD,Ph.D

Volitinib (HMPL-504) is a novel, highly potent and selective small molecule inhibitor of c-Met kinase. In preclinical studies, it demonstrated strong in vitro and in vivo activity against c-Met kinase and its downstream signaling targets and inhibited tumor cell growth. This first-in-human study is conducted to assess the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), to evaluate the pharmacokinetics, safety and preliminary anti-tumor activity of HMPL-504 at single doses and multiple doses.

This is a Phase I, first-in-human, open-label, dose-escalation study of Volitinib (HMPL-504) administered orally once every day(QD) to patients with locally advanced or metastatic solid tumors.There are two stages to this study : a dose-escalation stage and a dose-expansion stage. The dose-escalation stage is designed to evaluate the safety, tolerability, and pharmacokinetics of single dose and repeat doses of HMPL-504 given once every day (QD). An alternative dosing schedule of twice every day (BID) may be investigated if pharmacokinetic studies indicate faster than anticipated clearance of HMPL-504.

All patients will be carefully followed for adverse events during the study treatment and for 30 days after the last dose of study drug. Subjects of this study will be permitted to continue therapy with only safety monitoring and bimonthly assessments for progression, if the product is well tolerated and the subject has stable disease or better.

Phase I Study of the Volitinib (HMPL-504) in Patients With Advanced Solid Tumors

A Phase I, Open-label, Dose-escalation Study of the Safety and Pharmacokinetics of HMPL-504 in Patients With Advanced Solid Tumors

Anti-tumoral efficacy will be assessed by best radiographic response based on Response Evaluation Criteria in Solid Tumors at baseline (Day -14 to -1) and at the end of two 21-Day cycles of therapy . For patients that continue on repeat 21-Day cycles after the primary evaluation period, progression will be assessed after each one 21-Day cycles of therapy

The primary endpoint is evaluation of safety and tolerability during all the study of therapy following the initiation of multiple dosing of HMPL-504. The safety and tolerability variables to be evaluated in this study are adverse events, physical examinations, vital signs (specifically including blood pressure), clinical laboratory evaluations including serum chemistry, hematology(Maximum Tolerated Dose) , and urinalysis (with detailed sediment analysis, proteinuria, and 24-hour urine for collection for protein), and electrocardiograms (ECGs) in triplicate,Incidence and nature of DLTs(Dose-Limiting Toxicity),To determine the MTD (Maximum Tolerated Dose).

In the study of single-dose, full Pharmacokinetics(PK) profiles of HMPL-504 will be obtained following administration of a single oral dose of HMPL-504 on Day 1 to Day 3. At multiple-dose, Pharmacokinetics(PK) sampling will include a pre-dose and at the 0.5,2,4,6,8 hour time points on days 1,15,21of dosing in the first 21-Day cycle of therapy, and pre-dose on days 2,8,16,and 22 of the first 21-Day cycle of therapy

Sir Charles Gairdner Hospital

Austin Hospital, Melbourne Australia

Monash University

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Volitinib 800 mg will be administered orally once a day for 21 days as one cycle.

Volitinib is an orally available, potent, selective, small molecule c-MET inhibitor. Volitinib 800 mg will be administered orally once a day for 21 days as one cycle.

Jee yun Lee, MD,Ph.D.

Volitinib is a potent and selective small molecule c-Met kinase inhibitor. Volitinib was found to inhibit c-Met kinase at the enzyme and cell levels with IC50s of 4 nM for both enzyme and Met phosphorylation in the cell. Consistent with its potent enzyme and cell activity, volitinib was found to inhibit cell growth in vitro against tumors with c-Met gene amplification in the absence of HGF stimulation with IC50s generally below 10 nM. It also potently inhibited HGF-stimulated cell proliferation against tumors with c-Met overexpression or carrying a HGF/c-Met autocrine loop.

This study is a single-arm, phase II study of votilinib in patients with advanced gastric adenocarcinoma harboring MET amplification as a third line treatment Volitinib 800 mg will be administered orally once a day for 21 days as one cycle.

To investigate the efficacy of volitinib in patients with advanced gastric adenocarcinoma harboring MET amplification.

Study of AZD6094 (Volitinib) in Advanced Gastric Adenocarcinoma Patients With MET Amplification as a Third-line Treatment

Samsung Medical Center

MD,PhD

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Gefitinib

Cohort 1: Volitinib（AZD6094） 600 mg od + gefitinib 250 mg od

Cohort 2: Volitinib（AZD6094） 800 mg od + gefitinib 250 mg od

600mg or 800mg QD: Patients may continue to receive the treatment as long as they are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.

250mg QD: Patients may continue to receive the treatment as long as they are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.

gefitinib

Yilong Wu, Prof.

This is a Phase 1b, open-label, multicentre study of AZD6094 in combination with gefitinib in patients with epidermal growth factor receptor (EGFR) mutation positive (m+) and progressed on EGFR Tyrosine kinase inhibitor (TKI) treatment.

A total of 53 patients will be enrolled in the safety run-in and expansion phases:

* Safety run-in phase - patients with EGFR mutation-positive (EGFRm+), locally advanced or metastatic non-small cell lung cancer (NSCLC), who have progressed on previous EGFT TKI treatment.In the safety run-in phase of the study, the sample size may vary, depending on the number of dose levels evaluated and the number of Dose Limiting Toxicities (DLTs) observed in each cohort.
* Expansion phase - patients who are EGFRm+ and cMet-positive with locally advanced or metastatic NSCLC, who have progressed on previous EGFR-TKI treatment.

A Phase I Study of Safety and Pharmacokinetics of Volitinib in Combination With Gefitinib in EGFR(+) NSCLC

A Phase Ib, Open-label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumour Activity of Volitinib in Combination With Gefitinib in Patients With Epidermal Growth Factor Receptor-mutated Non-small Cell Lung Cancer Who Have Progressed on Epidermal Growth Factor Receptor Inhibitor Treatment

the grade of AE event according to CTC AE 4.0

Area under the plasma concentration versus time curve (AUC)

6-months PFS, 12 months PFS and 24 month PFS

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Safety and Pharmacokinetics of Volitinib With Docetaxel in Patients With Advanced Gastric Cancer	NCT02252913	Gastric Cancer	Volitinib Docetaxel	18 Years -	Hutchmed
Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib	NCT03778229	Carcinoma	osimertinib savolitinib placebo	18 Years -	AstraZeneca
Phase I Study of the Volitinib (HMPL-504) in Patients With Advanced Solid Tumors	NCT01773018	Tumor	Volitinib	18 Years -	Hutchmed
Study of AZD6094 (Volitinib) in Advanced Gastric Adenocarcinoma Patients With MET Amplification as a Third-line Treatment	NCT02449551	Advanced Gastri...	Volitinib	20 Years -	Samsung Medical Center
Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib	NCT03778229	Carcinoma	osimertinib savolitinib placebo	18 Years -	AstraZeneca
A Phase I Study of Safety and Pharmacokinetics of Volitinib in Combination With Gefitinib in EGFR(+) NSCLC	NCT02374645	Non-Small Cell ...	Volitinib gefitinib	18 Years -	Hutchmed

Spots Global Cancer Trial Database for volitinib

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

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