Advanced Gastric AdenocarcinomaPhase 2NCT02449655
Trial of AZD5363 Plus Paclitaxel /AZD2014 Plus Paclitaxel in Biomarker Negative (PIK3CA/MEK/RAS/TP53/MET) Gastric Adenocarcinoma Patients as Second-line Chemotherapy
A Phase 2 study testing AZD5363, paclitaxel and AZD2014 in people with Advanced Gastric Adenocarcinoma, run by Samsung Medical Center at 1 site in South Korea.
Trial summary
Phase II trial of AZD5363 plus paclitaxel / AZD2014 plus paclitaxel in biomarker negative (PIK3CA/MEK/RAS/TP53/MET) advanced gastric adenocarcinoma patients as second-line chemotherapy. Each arm is composed of 25 patients. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Advanced Gastric Adenocarcinoma
- What is being tested?
- AZD5363, paclitaxel and AZD2014
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteSouth Korea
- Study dates
- 12 Feb 2015to 16 Jul 2018
- 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 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 first line therapy.
- Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the first line therapy.
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- Provision of tumor sample (from either a resection or biopsy)
- Patients with biomarker negative
- Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
- 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.
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 PIK3CA, AKT or mTOR inhibitor 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
- Patients unable to swallow orally administered medication.
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- 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 denusomab 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 enrollment.
- For AZD2014: Exposure to potent or moderate inhibitors or inducers of CYP3A4/5 if taken within the stated washout periods before the first dose of study treatment
- 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.
- 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)
- Patients with proteinuria (3+ on dipstick analysis )
Trial locations and contacts
1 site in 1 country.
About this study
Phase II trial of AZD5363 plus paclitaxel / AZD2014 plus paclitaxel in biomarker negative (PIK3CA/MEK/RAS/TP53/MET) advanced gastric adenocarcinoma patients as second-line chemotherapy.
Each arm is composed of 25 patients.
Read more
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.
AZD2014 50mg BD 3 days on 4 days off of a 7 day cycle + paclitaxel 80mg/m2 given days 1, 8 and 15 of a 28 day cycle.
Tumour evaluation using Response Evaluation Criteria in Solid Tumors 1.1 will be conducted at screening (within 28 days prior to first dose) and every 8 weeks relative to the date of first dose, 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.
The purpose of this study is to investigate the safety and efficacy of AZD5363 plus paclitaxel in biomarker negative (PIK3CA/MEK/RAS/TP53/MET) advanced gastric adenocarcinoma patients as second-line chemotherapy.
Read the detailed description
AZD2014 is a selective dual mTOR kinase inhibitor targeting both mTORC1 (rapamycin sensitive) and mTORC2 (rapamycin insensitive) complexes of mammalian Target of Rapamycin (mTOR).
AZD2014 is a selective dual mTOR kinase inhibitor targeting both mTORC1 (rapamycin sensitive) and mTORC2 (rapamycin insensitive) complexes of mammalian Target Of Rapamycin (mTOR) AZD2014 is specific for mTOR and does not inhibit other members of the PI3K superfamily.
The PI3K-AKT-mTOR pathway functions as a sensor of mitogen, energy and nutrient levels and is a central controller of cell growth.
The mTOR is a protein kinase (PK) and a vital component of the PI3K/Akt/mTOR signaling pathway. This pathway is deregulated in 50% of all human cancers and, as such, is an important target for inhibitors that would alleviate the unregulated proliferation of cancer cells . AZD2014 is selective inhibitor of mTOR kinases and inhibits signalling of both mTOR complexes, mTORC1 and mTORC2.
In this study, the researchers further investigated the effect of PI3K/mTOR inhibitor as a paclitaxel sensitizer and/or nonspecific targeted therapy in combination with standard chemotherapy, paclitaxel in patients with pretreated advanced or metastatic gastric cancer having all negative biomarkers (PIK3CA/MEK/RAS/TP53/MET).
AZD5363 is a highly potent adenosine triphosphate (ATP)-competitive AKT inhibitor with IC50<10nmol/l for all three AKT isoforms.
AZD5363 is a highly potent adenosine triphosphate (ATP)-competitive AKT inhibitor with IC50<10nmol/l for all three AKT isoforms. AKT pathway is activated in various human cancers.Although AKT inhibitor has known showing anti-tumor activity in cell lines mutated at the E542, E545, or H1047 positions in preclinical study, clinical studies with AKT inhibitor are conducted for non-selected cancer patients.
- Conditions
- Advanced Gastric Adenocarcinoma
- Being tested
- AZD5363, paclitaxel, AZD2014
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD5363Drug
AZD5363 4800mg 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
AZD2014Drug
AZD2014 50mg BD 3 days on 4 days off of a 7 day cycle
paclitaxelDrug
paclitaxel 80mg/m2 given days 1, 8 and 15 of a 28 day cycle
| Study group | Role | What they receive |
|---|---|---|
| AZD5363 plus paclitaxel | Experimental | AZD5363 4800mg 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. Receives: Drug: AZD5363; Drug: paclitaxel |
| AZD2014 plus paclitaxel | Active comparator | AZD2014 50mg BD 3 days on 4 days off of a 7 day cycle + paclitaxel 80mg/m2 given days 1, 8 and 15 of a 28 day cycle Receives: Drug: AZD2014; Drug: paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR)
Measured: expected average of 24 weeks
Secondary outcomes (6)
Duration of response
Measured: expected average of 24 weeks
Disease control rate
Measured: 8 weeks
Overall survival (OS)
Measured: expected average of 24 weeks
progression-free survival (PFS)
Measured: expected average of 24 weeks
Biomarker analysis
responders vs non-responders with whole exome sequencing/RNA sequencing including re-biopsy specimens Lauren classification (intestinal vs diffuse)
Measured: 3 years
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.
- First posted20 May 2015 (estimated)
- Study start12 Feb 2015
- Primary completion16 Jul 2018
- Study completion16 Jul 2018
Why it stopped: lack of efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Gastric AdenocarcinomaStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Samsung Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jeeyun Lee, Samsung Medical Center
- Investigators
- Jee yun Lee, MD,Ph.D., Principal investigator, Samsung Medical Center,Seoul,Korea
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02449655
- Sponsor's protocol ID
- 2014-04-122
- Status last verified
- May 2019
- First submitted
- 14 May 2015
- Last updated
- 20 May 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial of AZD5363 Plus Paclitaxel /AZD2014 Plus Paclitaxel in Biomarker Negative (PIK3CA/MEK/RAS/TP53/MET) Gastric Adenocarcinoma Patients as Second-line Chemotherapy
- ClinicalTrials.gov ID
- NCT02449655
- Acronym / sponsor ID
- 2014-04-122
- Conditions
- Advanced Gastric Adenocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of efficacy
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Samsung Medical CenterUniversity, hospital or other
- Study start
- 12 Feb 2015 (actual)
- Primary completion
- 16 Jul 2018 (actual)
- Study completion
- 16 Jul 2018 (actual)
- First posted
- 20 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.
Phase II trial of AZD5363 plus paclitaxel / AZD2014 plus paclitaxel in biomarker negative (PIK3CA/MEK/RAS/TP53/MET) advanced gastric adenocarcinoma patients as second-line chemotherapy.
Each arm is composed of 25 patients.
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.
AZD2014 50mg BD 3 days on 4 days off of a 7 day cycle + paclitaxel 80mg/m2 given days 1, 8 and 15 of a 28 day cycle.
Tumour evaluation using Response Evaluation Criteria in Solid Tumors 1.1 will be conducted at screening (within 28 days prior to first dose) and every 8 weeks relative to the date of first dose, 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.
The purpose of this study is to investigate the safety and efficacy of AZD5363 plus paclitaxel in biomarker negative (PIK3CA/MEK/RAS/TP53/MET) advanced gastric adenocarcinoma patients as second-line chemotherapy.
Detailed description
AZD2014 is a selective dual mTOR kinase inhibitor targeting both mTORC1 (rapamycin sensitive) and mTORC2 (rapamycin insensitive) complexes of mammalian Target of Rapamycin (mTOR).
AZD2014 is a selective dual mTOR kinase inhibitor targeting both mTORC1 (rapamycin sensitive) and mTORC2 (rapamycin insensitive) complexes of mammalian Target Of Rapamycin (mTOR) AZD2014 is specific for mTOR and does not inhibit other members of the PI3K superfamily.
The PI3K-AKT-mTOR pathway functions as a sensor of mitogen, energy and nutrient levels and is a central controller of cell growth.
The mTOR is a protein kinase (PK) and a vital component of the PI3K/Akt/mTOR signaling pathway. This pathway is deregulated in 50% of all human cancers and, as such, is an important target for inhibitors that would alleviate the unregulated proliferation of cancer cells . AZD2014 is selective inhibitor of mTOR kinases and inhibits signalling of both mTOR complexes, mTORC1 and mTORC2.
In this study, the researchers further investigated the effect of PI3K/mTOR inhibitor as a paclitaxel sensitizer and/or nonspecific targeted therapy in combination with standard chemotherapy, paclitaxel in patients with pretreated advanced or metastatic gastric cancer having all negative biomarkers (PIK3CA/MEK/RAS/TP53/MET).
AZD5363 is a highly potent adenosine triphosphate (ATP)-competitive AKT inhibitor with IC50<10nmol/l for all three AKT isoforms.
AZD5363 is a highly potent adenosine triphosphate (ATP)-competitive AKT inhibitor with IC50<10nmol/l for all three AKT isoforms. AKT pathway is activated in various human cancers.Although AKT inhibitor has known showing anti-tumor activity in cell lines mutated at the E542, E545, or H1047 positions in preclinical study, clinical studies with AKT inhibitor are conducted for non-selected cancer patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AZD5363 plus paclitaxel | Experimental | Drug: AZD5363, Drug: paclitaxelAZD5363 4800mg 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. |
| AZD2014 plus paclitaxel | Active comparator | Drug: AZD2014, Drug: paclitaxelAZD2014 50mg BD 3 days on 4 days off of a 7 day cycle + paclitaxel 80mg/m2 given days 1, 8 and 15 of a 28 day cycle |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Provision of fully informed consent prior to any study specific procedures.
- Patients must be ≥20 years of age.
- Advanced gastric adenocarcinoma 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 first line therapy.
- Provision of tumor sample (from either a resection or biopsy)
Key exclusion criteria (18 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, AKT or mTOR inhibitor 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
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 |
|---|---|---|
| AZD5363AZD5363 4800mg bid 4 days on/ 3 days off of a 7 day cycle for each week | Drug | AZD5363 plus paclitaxel |
| paclitaxelpaclitaxel 80mg/m2 given days 1, 8 and 15 of a 28 day cycle | Drug | AZD5363 plus paclitaxel |
| AZD2014AZD2014 50mg BD 3 days on 4 days off of a 7 day cycle | Drug | AZD2014 plus paclitaxel |
| paclitaxelpaclitaxel 80mg/m2 given days 1, 8 and 15 of a 28 day cycle | Drug | AZD2014 plus paclitaxel |
Primary outcome
Objective response rate (ORR)
Time frame: expected average of 24 weeks
6 secondary outcomes
Duration of response
Time frame: expected average of 24 weeks
Disease control rate
Time frame: 8 weeks
Overall survival (OS)
Time frame: expected average of 24 weeks
progression-free survival (PFS)
Time frame: expected average of 24 weeks
Biomarker analysis
Time frame: 3 years
Number of subjects with Adverse Events as a measure of safety and tolerability
Time frame: expected average of 24 weeks
Results and safety
The study was stopped early (reason given: lack of efficacy). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 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.
Jee yun Lee, MD,Ph.D. principal investigator
Samsung Medical Center,Seoul,Korea
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, paclitaxel and AZD2014 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 21 inclusion and 18 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: stopped early, as of the sponsor's last update on 20 May 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 was stopped early (reason given: lack of efficacy). Results are not available in the source record.
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?
Objective 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 20 May 2019.