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

NCT03580239 | Unknown Phase 3 DMC FDA Drug

• 1 other identifier: CRPC-EVE
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 4

Brief Summary

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).

Conditions

Prostate Cancer

Keywords

CRPC; Everolimus; mTOR

Outcome Measures

Primary Outcomes (2)

• PFS

  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).

  36 months

• OS

  Overall Survival of the Participants

  36months

Secondary Outcomes (2)

• ORR

  36 months

• DCR

  36 months

Study Arms (2)

Everolimus & Best Supportive Care

EXPERIMENTAL

Everolimus 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.

Drug: Everolimus

Placebo & Best Supportive Care

PLACEBO COMPARATOR

Placebo 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.

Drug: Placebo

Interventions

Everolimus DRUG

Everolimus will be treated 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.

Also known as: Novartis Pharma Schweiz AG

Everolimus & Best Supportive Care

Placebo DRUG

Placebo will be treated 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 & Best Supportive Care

Eligibility Criteria

• Age: 18 Years - 75 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with advanced refractory castration resistant prostate cancer(CRPC).
• Patients with histologically or cytologically confirmed prostate cancer.
• 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.
• 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;
• 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.
• The expected survival time is more than 4 weeks.
• Patients with Karnofsky(KPS) functional status score \> 60 and Eastern Cooperative Oncology Group(ECOG)state score 0-2 points.
• 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.
• Patients who adherence to research and follow-up procedures.

You may not qualify if:

• Patients with other malignant tumors over the last 5 years.
• Patients who received chemotherapy, biotherapy or other anticancer drugs is less than 4 weeks.
• 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
• Patients with cognitive and psychological abnormality
• Patients who use other test drugs or participate in other clinical trials.
• 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).

Sponsors & Collaborators

• Tianjin Medical University Second Hospital: lead
• Tianjin Medical University General Hospital: collaborator
• Tianjin First Central Hospital: collaborator
• The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine，China: collaborator

Study Sites (4)

Tianjin First Center Hospital

Tianjin, Tianjin Municipality, 300000, China

Location

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, 300050, China

Location

The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine

Tianjin, Tianjin Municipality, 300150, China

Location

Tianjin Medical Unversity Second Hospital

Tianjin, Tianjin Municipality, 300200, China

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Central Study Contacts

Haitao Wang, Ph.D

CONTACT

+86-88326610; peterrock2000@126.com

Haitao Wang, Ph.D

CONTACT

+86-1860955984; peterrock2000@126.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2018
• First Posted: July 9, 2018
• Study Start: January 1, 2019
• Primary Completion: January 31, 2023
• Study Completion: December 1, 2023
• Last Updated: July 9, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)