Clinical Trials /

Everolimus in Castrated Resistant Prostate Cancer(CRPC)Patients With PI3K-AKT-mTOR Signaling Pathway Deficiency

NCT03580239

Description:

Investigators seek a new therapeutic strategy for castrated resistant prostate cancer(CRPC) patients with PI3K-AKT-mTOR signaling pathway deficiency by next generation sequencing(NGS).

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Everolimus in Castrated Resistant Prostate Cancer(CRPC)Patients With PI3K-AKT-mTOR Signaling Pathway Deficiency
  • Official Title: Placebo-Controlled, Randomized, Prospective and Multicenter Trial of Everolimus in Castrated Resistant Prostate Cancer Patients With PI3K-AKT-mTOR Signaling Pathway Deficiency

Clinical Trial IDs

  • ORG STUDY ID: CRPC-EVE
  • NCT ID: NCT03580239

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
EverolimusNovartis Pharma Schweiz AGEverolimus & Best Supportive Care
PlaceboPlacebo & Best Supportive Care

Purpose

Investigators seek a new therapeutic strategy for castrated resistant prostate cancer(CRPC) patients with PI3K-AKT-mTOR signaling pathway deficiency by next generation sequencing(NGS).

Detailed Description

      The prognosis of castrated resistant prostate cancer(CRPC) is very poor.Now,there is not an
      ideal therapeutic strategy.Further clarifying its mechanism and finding more effective
      therapeutic targets on this basis are the clinical problems to be solved urgently. More and
      more studies have confirmed that the role of PI3K-AKT-mTOR signaling pathway in the
      development of castration resistance to prostate cancer.By next generation sequencing of 115
      patients with CRPC, investigators found that 22% of the patients had mutations in the
      PI3K-AKT-mTOR signaling related genes.Investigators found that 50% of the patients could
      benefit from the mTOR inhibitors.But the specific clinical significance and molecular
      mechanism are urgently needed to be elucidated. This project is based on the hypothesis that
      Everolimus can target CRPC patients with PI3K-AKT-mTOR signaling pathways
      deficiency.So,investigators intend to peform a prospective, randomized,
      controlled,multicenter clinical study to find potential therapeutic targets and treatment
      strategies for CRPC patients.
    

Trial Arms

NameTypeDescriptionInterventions
Everolimus & Best Supportive CareExperimentalEverolimus will be administered at a dose of 10mg/day orally once a day. One cycle of therapy consists of 28 days.The patients also receive the best supportive care.
  • Everolimus
Placebo & Best Supportive CarePlacebo ComparatorPlacebo will be administered at a dose of 10mg/day orally once a day. One cycle of therapy consists of 28 days.The patients also receive the best supportive care.
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          1. Patients diagnosed with advanced refractory castration resistant prostate
             cancer(CRPC).

          2. Patients with histologically or cytologically confirmed prostate cancer.

          3. Conventional treatment failed advanced CRPC patients,routine treatment
             including:radical prostatic cancer surgery,castration, ADT, amieton /inololamine new
             endocrine therapy,docetaxel intravenous drug resistance, or intolerance of toxic and
             side effects.

          4. Patients must be able to provide blood samples or tissue samples for testing. The
             amount of blood samples should be able to meet the requirements of DNA extraction and
             quality control:

             I.Sample type: DNA samples without RNA degradation and pollution free.

             II.A single sample size of more than 500 ng (using Roche library platform,Illumina
             sequencing platform).

             III.The sample concentration is more than 40 ng/L (using Roche building database
             platform; Illumina sequencing platform); IV.The purity of the sample is OD
             260/280=1.8~2;

          5. After next generations of sequencing, all the patients were found to have defects in
             the PI3K-AKT-mTOR signaling pathway, including the following molecular markers: PI3K,
             AKT, mTOR, PTEN, TSC1, TSC2 and so on.

          6. The expected survival time is more than 4 weeks.

          7. Patients with Karnofsky(KPS) functional status score > 60 and Eastern Cooperative
             Oncology Group(ECOG)state score 0-2 points.

          8. Patients organ function level must comply with the following requirements:

             I.Hematological parameters: the absolute count of neutrophils is more than 1.5*109/L,
             platelets count is more than 80*109/L, hemoglobin is more than 9g/dL (which can be
             maintained by blood transfusion).

             II.Liver function: the upper limit of the normal value of total bilirubin less than
             1.5 times, the upper limit of normal value of alanine aminotransferase and glutamic
             pyruvic aminotransferase, less than 2.5 times the normal value, such as the liver
             metastasis and the upper limit of the normal value of the aminotransferase less than 5
             times; Child-Pugh grade of liver function: A and a better B grade (less than 7);
             Barcelona Clinic Liver Cancer(BCLC)staging: B-C stage.

             III.Renal function: creatinine is less than 1.25 times the normal upper limit, and the
             creatinine clearance rate is more than 60ml/min.

          9. Patients who adherence to research and follow-up procedures.

         10. Patients who can understand and voluntarily sign informed consent.

        Exclusion Criteria:

          1. Patients with other malignant tumors over the last 5 years.

          2. Patients who received chemotherapy, biotherapy or other anticancer drugs is less than
             4 weeks.

          3. Patients with the following and above conditions:

             I.Patients with symptomatic central nervous system metastases or spinal cord
             compression.

             II.Patients with peripheral neuropathy symptoms, grade NCI(National Cancer
             Institute)>gradeII.

             III.Patients with any unstable systemic disease (including active infection, poor
             control of hypertension,unstable angina,congestive heart failure, liver, kidney or
             metabolic diseases).

             IV.Patients with severe pulmonary interstitial changes, pulmonary fibrosis, and
             irreversible respiratory insufficiency.

             V.Patients who are not receiving oral administration, need high energy intravenous
             nutrition, have undergone previous operations affecting absorption, active
             gastrointestinal ulcer and chronic diarrhea.

             VI. Patients with serious, uncontrolled medical and infectious diseases. VII. Patients
             with severe electrolyte imbalance. VIII. Patients with diffuse intravascular
             coagulation. IX. Patients who known allergies to platinum and Everolimus targeted
             drugs

          4. Patients with cognitive and psychological abnormality

          5. Patients who use other test drugs or participate in other clinical trials.

          6. Researchers believe that subjects may not be able to complete the study or may not be
             able to comply with the requirements of this study (for management or other reasons).
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:PFS
Time Frame:36 months
Safety Issue:
Description:Progression free survival of All the Evaluable Participants.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0).(Note: the appearance of one or more new lesions is also considered progression).

Secondary Outcome Measures

Measure:ORR
Time Frame:36 months
Safety Issue:
Description:Objective Response Rate is defined as the proportion of patients with complete response(CR) or partial response(PR).
Measure:DCR
Time Frame:36 months
Safety Issue:
Description:Disease control is defined as the proportion of patients who had a best response rating of complete response, partial response, or stable disease, and lasted at least 4 weeks.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Tianjin Medical University Second Hospital

Trial Keywords

  • CRPC
  • Everolimus
  • mTOR

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