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

NCT02252913 | Completed Phase 1

• 1 other identifier: 2014-504-00CH1
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• safety and tolerability

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

  21days

Secondary Outcomes (1)

• PK parameters

  22 days

Study Arms (1)

Volitinib+docetaxel

EXPERIMENTAL

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

Drug: Volitinib; Drug: Docetaxel

Interventions

Volitinib DRUG

oral administration

Also known as: HMPL-504

Volitinib+docetaxel

Docetaxel DRUG

intravenous injection

Also known as: Taxotere

Volitinib+docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form
• Age ≥18 years
• Histologically or cytologically documented, locally advanced, or metastatic gastric cancer patients who have failed the first line platinum and fluoropyrimidine based treatment. Adjuvant or neoadjuvant chemotherapy will be considered as first line treatment for advanced disease if disease progression occurred during or within 6 months of treatment.
• In the dose expansion stage, patients must have positive cMet test results by a central laboratory
• Absolute neutrophil count (ANC) ≥ 1.5x109/L, hemoglobin ≥ 9 g/dL and platelet count ≥ 100x109/L
• Total bilirubin ≤ULN; SGOT (AST), SGPT (ALT), ≤ 1.5xULN; alkaline phosphatase (ALP) ≤ 2.5xULN
• Serum creatinine \<1.5xULN or creatinine clearance ≥50mls/minute; confirmation of creatinine clearance is only required when creatinine is \>1.5 ULN
• International normalized ratio (INR) ≤1.5xthe ULN or activated partial thromboplastin time (aPTT) ≤1.5xthe ULN. The INR applies only to patients who do not receive therapeutic anti-coagulation.
• Evaluable disease at dose escalation stage and measurable disease at dose expansion stage per RECIST v1.1
• ECOG performance status of 0, or 1
• Expected survival \> 3 months
• Male or female patients of child-producing potential must agree to double barrier contraception, condoms, intrauterine device (IUD), or contraceptives or other effective avoidance of pregnancy measures during the study and for 90 days after the last dose of treatment
• Female patients of child-producing potential must have a negative pregnancy test prior to start of dosing or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening:
• Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
• Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation

You may not qualify if:

• Prior taxane or cMet inhibitor therapy for advanced disease. Prior taxane containing regimen as adjuvant or neoadjuvant therapy can be allowed provided relapse occurred at least 6 months after therapy
• Co-existing malignancy or malignancies diagnosed within the last 3 years other than Gastric with the exception of skin basal cell carcinoma or cervical cancer in situ at dose expansion stage.
• Any anti-cancer therapy, including, but not limited to chemotherapy, hormonal therapy, target therapy, immunotherapy, biologic therapy, radiotherapy, or herbal therapy within 3 weeks prior to initiation of study treatment with the following exceptions:
• Hormone-replacement therapy or oral contraceptives
• Palliative radiation to bone metastases 2 weeks prior to Day 1
• Strong inducers or inhibitors of CYP3A4 or strong inhibitors of CYP1A2 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort). See appendix 5
• Adverse events from prior anti-cancer therapy that have not resolved to CTC AE Grade 1, except for alopecia
• Clinically significant active infection
• Known clinically significant history of liver disease, including viral or other hepatitis , current alcohol abuse, or cirrhosis
• Known human immunodeficiency virus（HIV）infection
• Pregnant or lactating women
• NYHA Class II or greater congestive heart failure
• History of myocardial infarction, unstable angina, stroke or transient ischemic attack within 6 months prior to study entry , or cardiac ventricular arrhythmias requiring medication
• Currently receiving treatment with therapeutic doses of warfarin sodium. Low molecular weight heparin (LMWH) is allowed
• Brain metastasis or spinal cord compression not definitively treated with surgery and/or radiation, or previously treated CNS metastases or spinal cord compression without evidence of stable disease (clinically stable imaging) for ≥ 14 days. Current leptomeningeal metastases.

Sponsors & Collaborators

• Hutchison Medipharma Limited: lead
• AstraZeneca: collaborator

Study Sites (1)

Fudan University Shanghai Cancer Hospital

Shanghai, 200032, China

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine; Docetaxel

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Jin Li, Prof.

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2014
• First Posted: September 30, 2014
• Study Start: September 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: April 8, 2016

Record last verified: 2016-04

Locations

CN (1)