Advanced Gastric CancerPhase 2NCT02451956
Study of AZD5363 in Combination With Paclitaxel, in Advanced Gastric Adenocarcinoma Patients Harboring PIK3CA Mutation and/or PIK3CA Amplification as a Second-line Chemotherapy
A Phase 2 study testing AZD5363 and paclitaxel in people with Advanced Gastric Cancer, run by Samsung Medical Center at 1 site in South Korea.
Trial summary
This study is a single arm, single center phase II study of AZD5363 in combination with paclitaxel in patients with advanced gastric adenocarcinoma harboring PIK3CA mutation or amplification as a second line chemotherapy. Patients will receive AZD 5363 plus weekly paclitaxel combination regimen. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Advanced Gastric Cancer
- What is being tested?
- AZD5363 and paclitaxel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteSouth Korea
- Study dates
- 7 Jan 2015to 24 May 2019
- Phase
- Phase 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older 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.
- Advanced gastric adenocarcinoma (including GEJ) that has progressed during or after first-line therapy.
- The 1st line regimen must have contained doublet 5-fluoropyrimidine and platinum based regimen.
- 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.
- Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the 1st line therapy.
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- Provision of tumor sample (from either a resection or biopsy)
- Patients with PIK3CA mutation and/or PIK3CA amplification
- Eastern Cooperative Oncology Group 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)
- 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 following up visits.
- Negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1.
- Patients of child-bearing potential should be using adequate contraceptive measures (two forms of highly reliable methods) should not be breast feeding and must have a negative pregnancy test prior to start of dosing.
- Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
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.
- In case of investigator's discretion, patient has a specific biomarker and meets all eligible criteria except for line of therapy, patient will be allowed. However, only 3rd line is allowed in this isolated cases. In the case of other, PI should confirm.
- Any previous treatment with PIK3CA and/or AKT inhibitors or agents with mixed PI3K / mTOR activity.
- Any previous treatment with paclitaxel
- 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 +)
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- Patients unable to swallow orally administered medication.
- Any investigational drug or product administered within 30 days or 5 half-lives, whichever is longer, of the first dose of AZD5363.
- 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.
- Previous major surgery within 4weeks prior to first dose.
- With the exception of alopecia, any ongoing toxicities (>Common Toxicity Criteria for Adverse Effects grade 1) caused by previous cancer therapy.
- Intestinal obstruction or Common Toxicity Criteria for Adverse Effects 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) Left ventricular ejection fraction <55% measured by echocardiography, 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.
- Active or untreated brain metastases or spinal cord compression Patients with treated brain metastases or spinal cord compression are eligible if they have minimal neurologic symptoms, evidence of stable disease (for at least 1 month) or response on follow-up scan, and require no corticosteroid therapy for ≥ 1 week.
- Patients with proteinuria (3+ on dipstick analysis )
- Female patients who are breast-feeding or child-bearing
- 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)
- Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Samsung Medical Center
Seoul, Seoul, Korea, Republic of, 135-710
About this study
This study is a single arm, single center phase II study of AZD5363 in combination with paclitaxel in patients with advanced gastric adenocarcinoma harboring PIK3CA mutation or amplification as a second line chemotherapy.
Patients will receive AZD 5363 plus weekly paclitaxel combination regimen. A arm is composed of 25 patients.
Tumour evaluation using RECIST 1.1 will be conducted at screening (within 28 days prior to first dose) and every 8 weeks relative to the date of enrollment, up to week 40, then every 16 weeks until objective disease progression (within a window of +/- 7 days of the scheduled date).
Study treatment will be continued until objective disease progression.
Read the detailed description
AZD5363 is a highly potent adenosine triphosphate (ATP)-competitive AKT inhibitor with IC50<10nmol/l for all three AKT isoforms.
AZD5363 is well designed to inhibit the important main signal pathway in various human cancer. AZD5363 is a specific inhibitor of the AKT pathway which is activated in a wide spectrum of tumours.The combination of AZD5363 to standard chemotherapy, paclitaxel, might improve the outcomes of 2nd line therapy in advanced gastric cancer patients .
- Conditions
- Advanced Gastric Cancer
- Being tested
- AZD5363, paclitaxel
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD5363Drug
Dosage and Schedule : AZD5363 400mg bid 4 days on/ 3 days off of a 7 day cycle for each week
paclitaxelDrug
paclitaxel 80mg/m2 given days 1, 8 and 15 of a 28 day cycle.
| Study group | Role | What they receive |
|---|---|---|
| AZD5363 in combination with paclitaxel | Experimental | AZD5363 400mg bid 4 days on/ 3 days off of a 7 day cycle for each week that paclitaxel is given + paclitaxel 80mg/m2 given days 1, 8 and 15 of a 28 day cycle. AZD5363 and paclitaxel will be received for 3 consecutive weeks, followed by one week off-therapy in 4-week cycles.If paclitaxel therapy is stopped then AZD5363 can be given on a 4on/3off continuous schedule. Receives: Drug: AZD5363; Drug: paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Object response rate (ORR)
Measured: expected average of 24 weeks
Secondary outcomes (5)
Duration of response
Measured: expected average of 24 weeks
Disease control rate
Measured: 8 weeks
Overall survival
Measured: expected average of 24 weeks
progression-free survival
Measured: expected average of 24 weeks
Number of subjects with Adverse Events as a Measure of safety and tolerability
Measured: up to 100 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2015 (estimated)
- Study start7 Jan 2015
- Primary completion24 May 2019
- Study completion24 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Gastric CancerStudies of the same condition, open and under way.
- More trials run by Samsung Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Samsung Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Seung tae Kim, Samsung Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02451956
- Sponsor's protocol ID
- 2014-04-128
- Status last verified
- Dec 2019
- First submitted
- 14 May 2015
- Last updated
- 30 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of AZD5363 in Combination With Paclitaxel, in Advanced Gastric Adenocarcinoma Patients Harboring PIK3CA Mutation and/or PIK3CA Amplification as a Second-line Chemotherapy
- ClinicalTrials.gov ID
- NCT02451956
- Acronym / sponsor ID
- 2014-04-128
- Conditions
- Advanced Gastric Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Samsung Medical CenterUniversity, hospital or other
- Study start
- 7 Jan 2015 (actual)
- Primary completion
- 24 May 2019 (actual)
- Study completion
- 24 May 2019 (actual)
- First posted
- 22 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a single arm, single center phase II study of AZD5363 in combination with paclitaxel in patients with advanced gastric adenocarcinoma harboring PIK3CA mutation or amplification as a second line chemotherapy.
Patients will receive AZD 5363 plus weekly paclitaxel combination regimen. A arm is composed of 25 patients.
Tumour evaluation using RECIST 1.1 will be conducted at screening (within 28 days prior to first dose) and every 8 weeks relative to the date of enrollment, up to week 40, then every 16 weeks until objective disease progression (within a window of +/- 7 days of the scheduled date).
Study treatment will be continued until objective disease progression.
Detailed description
AZD5363 is a highly potent adenosine triphosphate (ATP)-competitive AKT inhibitor with IC50<10nmol/l for all three AKT isoforms.
AZD5363 is well designed to inhibit the important main signal pathway in various human cancer. AZD5363 is a specific inhibitor of the AKT pathway which is activated in a wide spectrum of tumours.The combination of AZD5363 to standard chemotherapy, paclitaxel, might improve the outcomes of 2nd line therapy in advanced gastric cancer patients .
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AZD5363 in combination with paclitaxel | Experimental | Drug: AZD5363, Drug: paclitaxelAZD5363 400mg bid 4 days on/ 3 days off of a 7 day cycle for each week that paclitaxel is given + paclitaxel 80mg/m2 given days 1, 8 and 15 of a 28 day cycle. AZD5363 and paclitaxel will be received for 3 consecutive weeks, followed by one week off-therapy in 4-week cycles.If paclitaxel therapy is stopped then AZD5363 can be given on a 4on/3off continuous schedule. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Provision of fully informed consent prior to any study specific procedures.
- Patients must be ≥20 years of age.
- Advanced gastric adenocarcinoma (including GEJ) that has progressed during or after first-line therapy.
- Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the 1st line therapy.
- Provision of tumor sample (from either a resection or biopsy)
Key exclusion criteria (19 listed)
- 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 PIK3CA and/or AKT inhibitors or agents with mixed PI3K / mTOR activity.
- Any previous treatment with paclitaxel
- 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 +)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD5363Dosage and Schedule : AZD5363 400mg bid 4 days on/ 3 days off of a 7 day cycle for each week | Drug | AZD5363 in combination with paclitaxel |
| paclitaxelpaclitaxel 80mg/m2 given days 1, 8 and 15 of a 28 day cycle. | Drug | AZD5363 in combination with paclitaxel |
Primary outcome
Object response rate (ORR)
Time frame: expected average of 24 weeks
5 secondary outcomes
Duration of response
Time frame: expected average of 24 weeks
Disease control rate
Time frame: 8 weeks
Overall survival
Time frame: expected average of 24 weeks
progression-free survival
Time frame: expected average of 24 weeks
Number of subjects with Adverse Events as a Measure of safety and tolerability
Time frame: up to 100 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AZD5363 and paclitaxel in people with Advanced Gastric Cancer, 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 22 inclusion and 19 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 30 Dec 2019. 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 phase mean?
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?
Object response rate (ORR) (time frame: expected average of 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Dec 2019.