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Advanced Gastric AdenocarcinomaPhase 1/2NCT02447406

Phase Ib, Single-arm Study of AZD6094 (Volitinib) in Combination With Docetaxel, in Any Solid Cancer and Sequential Phase II, Single-arm Study of AZD6094 (Volitinib) in Combination With Docetaxel in Advanced Gastric Adenocarcinoma Patients With MET Amplification as a Second Line Treatment

A Phase 1/2 study testing AZD6094 and docetaxel in people with Advanced Gastric Adenocarcinoma, run by Samsung Medical Center at 1 site in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Phase Ib/II, single-arm study of AZD6094 (Volitinib) in combination with docetaxel, in advanced gastric adenocarcinoma patients with MET amplification as a second-line treatment. Read more about this study

Who is it for?
Ages Up to 20 years
Conditions the study is for
Advanced Gastric Adenocarcinoma
What is being tested?
AZD6094 and docetaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteSouth Korea
Study dates
30 Apr 2015to 20 Sep 2020
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 20 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Provision of fully informed consent prior to any study specific procedures.
  • Patients must be ≥20 years of age.
  • For Phase Ib: Have histologically or cytologically confirmed diagnosis of relapsed or refractory locally advanced or metastatic solid tumors for whom no alternative effective standard therapy is available or for whom standard therapy is considered unsuitable or intolerable.
  • Although it is preferred to enroll patients with solid tumors harboring MET amplification, this will not be an enrollment requirement.
  • For Phase II: Advanced gastric adenocarcinoma (including GEJ expand and maybe include in list of abbreviations) that has progressed during or after first-line therapy.
  • The 1st line regimen must have contained doublet 5-fluoropyrimidine and platinum based regimen.
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  • Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy containing doublet 5-fluoropyrimidine and platinum-based regimen could be considered as 1st line therapy.
  • Patients with gastric adenocarcinoma harboring MET amplification by MET FISH.
  • Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the 1st line therapy.
  • Provision or availability of biopsy sample for analysis; e.g mandatory pre-treatment biopsy, or available diagnostic biopsy of sufficient quantity/quality
  • Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
  • ECOG performance status 0-1.
  • Patients must have a life expectancy ≥ 3 months from proposed first dose date.
  • Patients must have acceptable bone marrow, liver and renal function measured within 28 days prior to administration of study treatment as defined below:
  • Haemoglobin ≥9.0 g/dL (transfusion allowed)
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • White blood cells (WBC) > 3 x 109/L
  • Platelet count ≥100 x 109/L (transfusion allowed)
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (does not include patients with Glibert's disease)
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN
  • Serum creatinine ≤1.5 x institutional ULN
  • At least one measurable lesion that can be accurately assessed by imaging or physical examination at baseline and follow up visits.
  • Negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1 for women of childbearing potential.
  • Provision of consent for mandatory biopsy at progression. (fresh frozen will be mandatory if clinically feasible)

Who cannot join

  • More than one prior chemotherapy regimen (except for adjuvant/neoadjuvant chemotherapy with more than 6 month wash out period) for the treatment of gastric cancer in the advanced setting.
  • Any previous treatment with MET inhibitors
  • Any previous treatment with docetaxel.
  • Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≤5 years.
  • HER2 positive patients (defined by HER2 3+ by immunohistochemistry or HER2 SISH +)
  • Patients unable to swallow orally administered medication.
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  • Treatment with any investigational product during the last 28 days before the enrollment (or a longer period depending on the defined characteristics of the agents used).
  • Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 3 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment.
  • With the exception of alopecia, any ongoing toxicities (>CTCAE grade 1) caused by previous cancer therapy.
  • Intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4 weeks before the enrollment.
  • Resting ECG with measurable QTcB > 480 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
  • Patients with cardiac problem as follows: uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy) Baseline Left ventricular ejection fraction below the LLN of <55% measured by echocardiography or institution's LLN for MUGA, Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest , Symptomatic heart failure (NYHA grade II-IV), Prior or current cardiomyopathy, Severe valvular heart disease, Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy), Acute coronary syndrome within 6 months prior to starting treatment
  • Female patients who are breast-feeding or child-bearing and Male or female patients of reproductive potential who are not employing an effective method of contraception
  • Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses or renal transplant, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
  • Patients currently receiving (or unable to stop use at least 2 weeks) prior to receiving the first dose of AZD6094, medications known to be potent inhibitors of CYP1A2 or CYP3A4, potent inducers of CYP3A4 or CYP3A4 substrates with a narrow therapeutic range.

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Samsung Medical Center

    Seoul, Seoul, Korea, Republic of, 135-710

Other trials in South Korea

About this study

Phase Ib/II, single-arm study of AZD6094 (Volitinib) in combination with docetaxel, in advanced gastric adenocarcinoma patients with MET amplification as a second-line treatment.

Phase Ib:Investigational product, dosage and mode of administration Volitinib is an orally available, potent, selective, small molecule c-MET inhibitor.

Read more

Volitinib should be administered at least 200mg orally once a day in 21 days for achieving appropriate antitumor activity.

Docetaxel 60 mg/m2 will be administered via intravenous access once every 3 weeks Phase II: Investigational product, dosage and mode of administration Volitinib is an orally available, potent, selective, small molecule c-MET inhibitor. Subjects will receive Volitinib once daily ( at the MTD determined from Phase Ib) for 21 days as one cycle.

Docetaxel 60 mg/m2 will be administered via intravenous access once every 3 weeks.

Read the detailed description

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.

In a xenograft model Hs746T with c-Met gene amplification, suboptimal doses 0.6 mg/kg volitinib and 3 mg/kg docetaxel induced TGI(expand) of 55.8% and 80.8%, respectively, whereas combination resulted in a TGI by 101.1%, and statistical significance was seen between combination group and either of mono-therapy group. Plasma exposures of volitinib and docetaxel were determined after last dose at the end of study, and there was no significant difference between combination and single agent on exposures of either volitinib or docetaxel. More importantly, combination was well tolerant and no body weight loss was found in the animals. These results suggested that it would be worthwhile to study the combination use of volitinib and docetaxel in clinic.

Being tested
AZD6094, docetaxel

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD6094Drug

    Also called Volitinib

  • docetaxelDrug

Study groups in NCT02447406
Study groupRoleWhat they receive
AZD6094 (Volitinib) in combination with docetaxelExperimentalPhase Ib:Volitinib should be administered at least 200mg orally once a day in 21 days for achieving appropriate antitumor activity. Phase II: Subjects will receive Volitinib once daily ( at the MTD determined from Phase Ib) for 21 days as one cycle. Docetaxel 60 mg/m2 will be administered via intravenous access once every 3 weeks.
Receives: Drug: AZD6094; Drug: docetaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Hematologic toxicity and non-hematologic toxicity according to NCI-CTCAE version 4.0

    To determine maximal tolerate dose (MTD) of volitinib when given in combination with fixed dose of docetaxel in any solid cancer

    Measured: expected average of 24 weeks

  2. Objective response rate (ORR) by RECIST 1.1

    Phase II:To investigate the efficacy of volitinib when given in combination with docetaxel in patients with advanced gastric adenocarcinoma harboring MET amplification

    Measured: expected average of 24 weeks

Secondary outcomes (5)

  1. Duration of response

    Measured: expected average of 24 weeks

  2. Disease control rate

    Measured: 8 weeks

  3. Overall survival (OS)

    Measured: expected average of 24 weeks

  4. progression-free survival (PFS)

    Measured: expected average of 24 weeks

  5. Number of subjects with Adverse Events as a Measure of safety and tolerability

    Measured: expected average of 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2015 (estimated)
  2. Study start30 Apr 2015
  3. Primary completion30 Jun 2020
  4. Study completion20 Sep 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02447406
Sponsor's protocol ID
2014-07-169
Status last verified
Jun 2022
First submitted
14 May 2015
Last updated
15 Jun 2022
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AZD6094 and docetaxel in people with Advanced Gastric Adenocarcinoma, run by Samsung Medical Center at 1 site in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hematologic toxicity and non-hematologic toxicity according to NCI-CTCAE version 4.0 (time frame: expected average of 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02447406.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2022.

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