Clinical Trials /

Study of AZD5363 in Combination With Paclitaxel, in Advanced Gastric Adenocarcinoma Patients Harboring PIK3CA Mutation and/or PIK3CA Amplification as a Second-line Chemotherapy

NCT02451956

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Unknown status

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief 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
  • Official Title:

Clinical Trial IDs

  • ORG STUDY ID: 2014-04-128
  • NCT ID: NCT02451956

Conditions

  • Advanced Gastric Cancer

Interventions

DrugSynonymsArms
AZD5363AZD5363 in combination with paclitaxel
paclitaxelAZD5363 in combination with paclitaxel

Purpose

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 .
    

Trial Arms

NameTypeDescriptionInterventions
AZD5363 in combination with paclitaxelExperimentalAZD5363 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.
  • AZD5363
  • paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          1. Provision of fully informed consent prior to any study specific procedures.

          2. Patients must be ≥20 years of age.

          3. 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.

          4. Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months
             prior to starting the 1st line therapy.

          5. Provision of tumor sample (from either a resection or biopsy)

          6. Patients with PIK3CA mutation and/or PIK3CA amplification

          7. Eastern Cooperative Oncology Group performance status 0-1.

          8. Patients must have a life expectancy ≥ 3 months from proposed first dose date.

          9. 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

         10. At least one measurable lesion that can be accurately assessed by imaging or physical
             examination at baseline and following up visits.

         11. 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.

         12. Patients are willing and able to comply with the protocol for the duration of the
             study including undergoing treatment and scheduled visits and examinations.

        Exclusion Criteria:

          1. 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.

          2. Any previous treatment with PIK3CA and/or AKT inhibitors or agents with mixed PI3K /
             mTOR activity.

          3. Any previous treatment with paclitaxel

          4. 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.

          5. HER2 positive patients (defined by HER2 3+ by immunohistochemistry or HER2 SISH +)

          6. Patients unable to swallow orally administered medication.

          7. Any investigational drug or product administered within 30 days or 5 half-lives,
             whichever is longer, of the first dose of AZD5363.

          8. 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.

          9. Previous major surgery within 4weeks prior to first dose.

         10. With the exception of alopecia, any ongoing toxicities (>Common Toxicity Criteria for
             Adverse Effects grade 1) caused by previous cancer therapy.

         11. Intestinal obstruction or Common Toxicity Criteria for Adverse Effects grade 3 or
             grade 4 upper GI bleeding within 4 weeks before the enrollment.

         12. 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.

         13. 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.

         14. 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.

         15. Patients with proteinuria (3+ on dipstick analysis )

         16. Female patients who are breast-feeding or child-bearing

         17. 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)

         18. Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole,
             ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Object response rate (ORR)
Time Frame:expected average of 24 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Duration of response
Time Frame:expected average of 24 weeks
Safety Issue:
Description:
Measure:Disease control rate
Time Frame:8 weeks
Safety Issue:
Description:
Measure:Overall survival
Time Frame:expected average of 24 weeks
Safety Issue:
Description:
Measure:progression-free survival
Time Frame:expected average of 24 weeks
Safety Issue:
Description:
Measure:Number of subjects with Adverse Events as a Measure of safety and tolerability
Time Frame:up to 100 weeks
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Samsung Medical Center

Last Updated

February 15, 2017