Solid TumorPhase 1/2NCT04526470
Alpelisib and Paclitaxel in PIK3CA-altered Gastric Cancer
A Phase 1/2 study testing Alpelisib and Paclitaxel in people with Solid Tumor and Stomach Cancer, run by Seoul National University Bundang Hospital at 2 sites in South Korea.
Trial summary
Alpelisib (BYL719) is a PIK3CA-specific inhibitor, which was developed by Novartis (Basel, Switzerland). Our group conducted pre-clinical study of alpelisib in eight gastric cancer cell lines: four PIK3CA wild-type (SNU638, SNU668, SNU1, and SNU16) and four PIK3CA mutant (SNU719, AGS, SNU601, and MKN). Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Solid Tumor, Stomach Cancer
- What is being tested?
- Alpelisib and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 2 sitesSouth Korea
- Study dates
- 1 Sep 2020to Dec 2024
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject has signed the Informed Consent Form (ICF) prior to any screening procedures being performed
- Age ≥ 20 years old of male and female
- At each phase of the trial, subjects who meet the following requirements in each phase will be enrolled.
- Phase IB: Subjects with a histologically-confirmed, advanced/recurrent solid tumor who have progressed on standard therapy or whose disease does not have established standard therapy.
- Phase II: Subjects with histologically confirmed locally advanced or metastatic gastric cancer that have progressed after treatment with first-line fluoropyrimidine-based chemotherapy (Tissue samples of gastric cancer must contain PIK3CA gene alterations (e.g. single nucleotide variants, small indels, amplifications, structural variations, etc.) identified by central or local next generation sequencing (NGS). If the subject received adjuvant chemotherapy after curative gastric resection and lymph node dissection, the adjuvant chemotherapy is considered to be the first-line palliative chemotherapy if the disease recurred during adjuvant chemotherapy or within 6 months after the completion of adjuvant chemotherapy.
- Phase IB: Patient has evaluable disease as per RECIST 1.1. (Measurable lesions are not mandatory for study inclusion.) Phase II: Patient has at least one measurable lesion as per RECIST 1.1.
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- ECOG performance status 0-1
- Patient has adequate bone marrow and organ function as defined by the following laboratory values:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Hemoglobin ≥ 9.0 g/dL
- Platelet ≥ 100 x 109/L
- Serum creatinine ≤ ULN (upper limit of normal) or serum creatinine clearance ≥50 mL/min (by Cockcroft-Gault formula, or 24h urine collection)
- Total bilirubin: ≤ 1.5 × ULN Subjects with a bile duct obstruction will be eligible if they meet the criteria after appropriate bile drainage; Patients with Gilbert syndrome should also be included after confirming that the total bilirubin level is ≤ 1.5 x ULN in a follow-up screening test.
- Phase Ib: Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) ≤ 3 x ULN (regardless of liver metastases)
- Phase II: AST and ALT ≤ 3 x ULN if liver metastases are absent, or AST and ALT ≤ 5 x ULN if liver metastases are present.
- The subject is able to swallow and retain oral medication
- Serum β-HCG test negative within 14 days before the first administration of the study treatment (women of childbearing potential only).
- Requirement for contraception must be observed by the subject.
Who cannot join
- Patient has received previous treatment with a PI3K or AKT inhibitor. (Note: prior mTOR inhibitor treatment is allowed.)
- Patient has a known or suspicious hypersensitivity to paclitaxel or other products containing Cremophor.
- Any cytotoxic chemotherapy from a previous treatment regimen within 14 days. If the subject received an investigational drug from another clinical trial, the subject can be enrolled after 2 weeks of last administration and more than 5 x half-life of the investigational drug. If monoclonal antibody therapy was given, the subject can be enrolled after four weeks after the last does.
- Active central nervous system (CNS) lesions (i.e., those with radiologically unstable or symptomatic brain lesions). For those who receive radiation or surgical treatment, the subject can be enrolled if the subject is maintained without steroid therapy and the evidence of CNS disease progression for more than 4 weeks. However, patients with leptomeningeal metastases are excluded.
- Patient has not recovered to ≤ grade 1 (except alopecia) from related adverse effects of any prior antineoplastic therapy
- Radiotherapy with a wide field (more than 30% of the bone marrow) of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment.
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- Patient who has undergone major surgery ≤ 4 weeks prior to starting study treatment or who has not recovered from adverse effects of such procedure.
- Patient has a clinically significant cardiac disease or impaired cardiac function, such as:
- Acute coronary syndrome within the 6 months prior to the initiation of study drug (including myocardial infarction or unstable angina, Coronary Artery Bypass Graft surgery, percutaneous coronary intervention and stenting)
- Heart failure ≥ grade 2 by New York Heart Association (NYHA) functional classification or that requires treatment
- Ejection fraction (EF) <50% on multi-gated acquisition (MUGA) scan or echocardiography examination. MUGA scan or echocardiography is not required as a screening test if there is no current suspicious symptom and past history of heart failure.
- Persistent uncontrolled hypertension as defined by: systolic >180 mmHg or diastolic >100 mmHg despite medical treatment
- Current or past history of clinically significant cardiac arrhythmia, atrial fibrillation, and/or conduction abnormality including complete AV block, long QT syndrome, congenital long QT syndrome, or QTcF >470 msec at screening (if the average QTcF value > 470 msec by measuring 3 times consecutively in total).
- Any risk factors that prolong QTc or increase the probability of arrhythmia, including medication (e.g. heart failure, hypokalemia, congenital long QT syndrome, history of Torsades de Pointes)
- If the subject was diagnosed with diabetes (irrespective of treatment or symptom) or if the subject has ① Korean Diabetes Prediction Score (Appendix A) more than 7 plus impaired glucose tolerance (with blood glucose of 140-199 mg/dL after 2-hour oral glucose tolerance test (75g)), ② previous history of gestational diabetes, or ③ steroid-induced diabetes.
- Patients with impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral BYL719 (e.g. untreated peptic ulcer disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or wide small bowel resection).
- Patient has a known positive serology for human immunodeficiency virus (HIV), active Hepatitis B, and/or active Hepatitis C infection. Hepatitis B carriers may be enrolled if prophylactic use of an antiviral agent with minimal interaction with CYP3A4 is administered to inhibit HBV activation (e.g., entecavir, adefovir)
- Concomitant medication of strong or moderate inducers or inhibitors of CYP3A4 (Table 11) before the first dose of study treatment (In this case, if the drug is stopped for 1 week or more (according to Table 11) and changed to another drug that does not affect CYP3A4, then the subject can be enrolled.)
- History of other primary cancer. Exceptions are as follows:
- Adequately treated non-melanoma skin cancer (basal cell or squamous cell carcinoma), curatively treated in situ cancer of the cervix or stage I bladder cancer, completely resected thyroid cancer without distant metastasis in which all treatment has been completed (Appropriate wound healing is required prior to clinical trial enrollment)
- Other curatively treated solid tumors except for gastric cancer with no evidence of disease recurrence at least 24 months before participating in this trial
- History of allogeneic bone marrow transplantation or organ transplantation
- As judged by the Investigator, all other symptoms and associated disease for which the investigator determined that participation in this study is contraindicated (e.g. Infection/inflammation; severe liver dysfunction; bilateral diffuse interstitial lung disease; uncontrolled renal disease; unstable heart and lung disease; hemorrhagic disease; intestinal obstruction; unable to swallow oral pills; social and psychological problems, etc.)
- Medical, psychiatric, cognitive, or other conditions that may interfere with the ability of the subject to understand the subject information, provide the informed consent, follow the protocol process, or complete the clinical trial
Trial locations and contacts
2 sites in 1 country.
South Korea2 sites, 2 recruiting
- Recruiting
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
Keun-Wook Lee, MD. & Ph.D, 82-31-787-7039, hmodoctor@snubh.org
- Recruiting
Asan Medical Center
Seoul, 05505
Min-Hee Ryu, MD. & Ph.D., miniryu@amc.seoul.kr
About this study
Official title: Phase IB/II Study of Alpelisib in Combination With Paclitaxel in Patients With PIK3CA-altered Metastatic/Recurrent Gastric Cancer
Alpelisib (BYL719) is a PIK3CA-specific inhibitor, which was developed by Novartis (Basel, Switzerland). Our group conducted pre-clinical study of alpelisib in eight gastric cancer cell lines: four PIK3CA wild-type (SNU638, SNU668, SNU1, and SNU16) and four PIK3CA mutant (SNU719, AGS, SNU601, and MKN). As a result, alpelisib preferentially inhibited the growth of gastric cancer cells with PIK3CA mutations. In addition, alpelisib inhibited cell growth via G1 arrest and subsequently induces apoptosis in GC cells, and this effect is more remarkable in cells harboring PIK3CA mutations. Moreover, alpelisib in combination with paclitaxel showed synergistic cytotoxic effects and significantly increased apoptosis compared with alpelisib or paclitaxel monotherapy in GC cells.
The purpose of the study is to define the maximal tolerated dose (MTD) and recommended phase II dose (RP2D) of paclitaxel and alpelisib combination therapy in patients with advanced tumors and to evaluate the efficacy of paclitaxel and AZD8186 combination therapy as a second-line therapy in patients with advanced gastric cancer with PTEN aberrations. This study is divided into Phase IB and Phase II.
- Conditions
- Solid Tumor, Stomach Cancer
- Being tested
- Alpelisib, Paclitaxel
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlpelisibDrug
Dose level -2: 200 mg PO once daily / Dose level -1: 200 mg PO once daily / Dose level 0: 250 mg PO once daily / Dose level 1: 300 mg PO once daily
PaclitaxelDrug
Dose level -2: 60 mg/m2 IV on day 1, 8, and 15 / Dose level -1: 70 mg/m2 IV on day 1, 8, and 15 / Dose level 0: 70 mg/m2 IV on day 1, 8, and 15 / Dose level 1: 70 mg/m2 IV on day 1, 8, and 15
| Study group | Role | What they receive |
|---|---|---|
| Alpelisib + Paclitaxel | Experimental | Phase IB is planned for a 4-stage dose level and the traditional 3+3 design is applied. The RP2D of alpelisib will be determined based on the MTD and toxicity profiles.
In phase II part, RP2D from the phase IB part will be applied as follows: alpelisib ( ) mg PO bid daily + paclitaxel ( ) mg/m² IV on D1, 8, and 15 every 4 weeks. Receives: Drug: Alpelisib; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal tolerated dose (MTD) and recommended phase 2 dose (RP2D)
Phase IB
Measured: 4 weeks
Progression-free survival rate at 4 months
Phase II
Measured: 4 months
Secondary outcomes (12)
Dose-limiting toxicity (DLT) of alpelisib and paclitaxel by NCI CTCAE version 4.03
Phase IB
Measured: 4 weeks
Rate of adverse events of all grade by NCI CTCAE version 4.03
Phase IB/II
Measured: during treatment
Peak plasma concentration (Cmax) of alpelisib
Phase IB
Measured: during treatment
Trough plasma concentration (Ctrough) of alpelisib
Phase IB
Measured: during treatment
Area under the plasma concentration versus time curve (AUC) of alpelisib
Phase IB
Measured: during treatment
Preliminary anti-tumor activity of alpelisib plus paclitaxel combination
Phase IB
Measured: during treatment
Overall survival
Phase II
Measured: during treatment
Progression-free survival
Phase II
Measured: during treatment
Objective response rate
Phase II
Measured: during treatment
Disease control rate
Phase II
Measured: during treatment
Duration of response
Phase II
Measured: during treatment
Time to response
Phase II
Measured: during treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2020
- Study start1 Sep 2020
- Primary completionJun 2023 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- More trials run by Seoul National University Bundang HospitalThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Seoul National University Bundang Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Keun-Wook Lee, Seoul National University Bundang Hospital
- Investigators
- Keun-Wook Lee, MD, PhD, Principal investigator, Seoul National University Bundang Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04526470
- Sponsor's protocol ID
- B-2004/604-002
- Status last verified
- Aug 2021
- First submitted
- 17 Aug 2020
- Last updated
- 24 Aug 2021
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IB/II Study of Alpelisib in Combination With Paclitaxel in Patients With PIK3CA-altered Metastatic/Recurrent Gastric Cancer
- ClinicalTrials.gov ID
- NCT04526470
- Acronym / sponsor ID
- B-2004/604-002
- Conditions
- Solid Tumor, Stomach Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- Seoul National University Bundang HospitalUniversity, hospital or other
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- Jun 2023 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 25 Aug 2020 (actual)
- 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.
Alpelisib (BYL719) is a PIK3CA-specific inhibitor, which was developed by Novartis (Basel, Switzerland). Our group conducted pre-clinical study of alpelisib in eight gastric cancer cell lines: four PIK3CA wild-type (SNU638, SNU668, SNU1, and SNU16) and four PIK3CA mutant (SNU719, AGS, SNU601, and MKN). As a result, alpelisib preferentially inhibited the growth of gastric cancer cells with PIK3CA mutations. In addition, alpelisib inhibited cell growth via G1 arrest and subsequently induces apoptosis in GC cells, and this effect is more remarkable in cells harboring PIK3CA mutations. Moreover, alpelisib in combination with paclitaxel showed synergistic cytotoxic effects and significantly increased apoptosis compared with alpelisib or paclitaxel monotherapy in GC cells.
The purpose of the study is to define the maximal tolerated dose (MTD) and recommended phase II dose (RP2D) of paclitaxel and alpelisib combination therapy in patients with advanced tumors and to evaluate the efficacy of paclitaxel and AZD8186 combination therapy as a second-line therapy in patients with advanced gastric cancer with PTEN aberrations. This study is divided into Phase IB and Phase II.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Alpelisib + Paclitaxel | Experimental | Drug: Alpelisib, Drug: PaclitaxelPhase IB is planned for a 4-stage dose level and the traditional 3+3 design is applied. The RP2D of alpelisib will be determined based on the MTD and toxicity profiles. In phase II part, RP2D from the phase IB part will be applied as follows: alpelisib ( ) mg PO bid daily + paclitaxel ( ) mg/m² IV on D1, 8, and 15 every 4 weeks. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Subject has signed the Informed Consent Form (ICF) prior to any screening procedures being performed
- Age ≥ 20 years old of male and female
- At each phase of the trial, subjects who meet the following requirements in each phase will be enrolled.
- Phase IB: Patient has evaluable disease as per RECIST 1.1. (Measurable lesions are not mandatory for study inclusion.) Phase II: Patient has at least one measurable lesion as per RECIST 1.1.
- ECOG performance status 0-1
Key exclusion criteria (24 listed)
- Patient has received previous treatment with a PI3K or AKT inhibitor. (Note: prior mTOR inhibitor treatment is allowed.)
- Patient has a known or suspicious hypersensitivity to paclitaxel or other products containing Cremophor.
- Any cytotoxic chemotherapy from a previous treatment regimen within 14 days. If the subject received an investigational drug from another clinical trial, the subject can be enrolled after 2 weeks of last administration and more than 5 x half-life of the investigational drug. If monoclonal antibody therapy was given, the subject can be enrolled after four weeks after the last does.
- Active central nervous system (CNS) lesions (i.e., those with radiologically unstable or symptomatic brain lesions). For those who receive radiation or surgical treatment, the subject can be enrolled if the subject is maintained without steroid therapy and the evidence of CNS disease progression for more than 4 weeks. However, patients with leptomeningeal metastases are excluded.
- Patient has not recovered to ≤ grade 1 (except alopecia) from related adverse effects of any prior antineoplastic therapy
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 |
|---|---|---|
| AlpelisibDose level -2: 200 mg PO once daily / Dose level -1: 200 mg PO once daily / Dose level 0: 250 mg PO once daily / Dose level 1: 300 mg PO once daily | Drug | Alpelisib + Paclitaxel |
| PaclitaxelDose level -2: 60 mg/m2 IV on day 1, 8, and 15 / Dose level -1: 70 mg/m2 IV on day 1, 8, and 15 / Dose level 0: 70 mg/m2 IV on day 1, 8, and 15 / Dose level 1: 70 mg/m2 IV on day 1, 8, and 15 | Drug | Alpelisib + Paclitaxel |
Primary outcome
Maximal tolerated dose (MTD) and recommended phase 2 dose (RP2D)
Time frame: 4 weeks
Phase IB
Progression-free survival rate at 4 months
Time frame: 4 months
Phase II
12 secondary outcomes
Dose-limiting toxicity (DLT) of alpelisib and paclitaxel by NCI CTCAE version 4.03
Time frame: 4 weeks
Rate of adverse events of all grade by NCI CTCAE version 4.03
Time frame: during treatment
Peak plasma concentration (Cmax) of alpelisib
Time frame: during treatment
Trough plasma concentration (Ctrough) of alpelisib
Time frame: during treatment
Area under the plasma concentration versus time curve (AUC) of alpelisib
Time frame: during treatment
Preliminary anti-tumor activity of alpelisib plus paclitaxel combination
Time frame: during treatment
Overall survival
Time frame: during treatment
Progression-free survival
Time frame: during treatment
Objective response rate
Time frame: during treatment
Disease control rate
Time frame: during treatment
Duration of response
Time frame: during treatment
Time to response
Time frame: during treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2021.
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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.
Keun-Wook Lee, MD, PhD principal investigator
Seoul National University Bundang Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Alpelisib and Paclitaxel in people with Solid Tumor and Stomach Cancer, run by Seoul National University Bundang Hospital at 2 sites 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 18 inclusion and 24 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: status not confirmed, as of the sponsor's last update on 24 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yong Min Shin (+82-31-787-8324, r0012@snubh.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal tolerated dose (MTD) and recommended phase 2 dose (RP2D) (time frame: 4 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?
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 24 Aug 2021.