Selective Treatment According to Molecular Subtype of Prostate Cancer (STAMP)

This is an open-label study that includes three substudies of random distribution. First, a sample of the primary tumor will be obtained and will be analyzed by an immunohistochemical technique to determine several markers. Depending on the expression of these markers, the patients will be characterize as group 1 (Luminal phenotype), group 2 (Neuroendocrine phenotype) or group 3 (Atypical phenotype) and a random assignment will be performed to standard or experimental treatment.

Study Overview

• Status: Recruiting
• Conditions: Castration-resistant Prostate Cancer; Prostate Cancer Metastatic
• Intervention / Treatment: Drug: Luminal type-1; Drug: Luminal type-2; Drug: Neuroendocrine type-1; Drug: Neuroendocrine type-2; Drug: Atypical type-1; Drug: Atypical type-2

Detailed Description

Metastatic castration-resistant prostate cancer (mCRPC) is a heterogenous disease with at least 3 intrinsic subtypes including luminal, neuroendocrine, and atypical phenotypes. Different subtypes have different prognosis and treatment sensitivity. Thus, it would be more suitable to administer different therapy in different subtypes. Therefore, the investigators designed this phase 2 randomized clinical trial to explore potential effective regimens in variable subtypes of mCRPC. Patients were first classified into Luminal type, Neuroendocrine type and Atypical type by immunohistochemistry exam of FKBP5/AR-WT/AR-v7/CgA/SYN/YAP1 in core needle biopsy and then randomized to received either standard or experimental treatment.

1. Group 1 (Luminal type):

   Standard treatment: Goserelin (3.75mg, once every 4 weeks)+Docetaxel (75 mg/m2 on day 1 every 3 weeks)+Prednisone (5 mg, twice daily)

   Experimental treatment: Goserelin (3.75mg, once every 4 weeks)+Abiraterone (1000 mg, once daily)+Prednisone (5 mg, twice daily)

2. Group 2 (Neuroendocrine type):

   Standard treatment: Goserelin (3.75mg, once every 4 weeks)+Docetaxel (75 mg/m2 on day 1 every 3 weeks)+Prednisone (5 mg, twice daily)

   Experimental treatment: Goserelin (3.75mg, once every 4 weeks)+Carboplatin (area under the curve 5 on day 1 every 3 weeks)+Docetaxel (75 mg/m2 on day 1 every 3 weeks)+Prednisone (5 mg, twice daily)

3. Group 3 (Atypical type):

Standard treatment: Goserelin (3.75mg, once every 4 weeks)+Docetaxel (75 mg/m2 on day 1 every 3 weeks)+Prednisone (5 mg, twice daily)

Experimental treatment: Goserelin (3.75mg, once every 4 weeks)+Abiraterone (1000 mg, once daily)+targeted therapy according to next Generation Sequencing (NGS)+Prednisone (5 mg, twice daily); or Goserelin (3.75mg, once every 4 weeks)+Abiraterone alone+Prednisone (5 mg, twice daily) if no druggable gene mutation detected. The detailed Individual treatment see below.

The duration of chemotherapy is 6-10 cycles. Primary endpoint is the overall survival (OS) in each subtypes. Secondary endpoints include progression free survival (PFS), PSA response rate and safety. Tissue samples and blood samples will be collected at baseline and during treatment. There will be exploratory biomarkers analyses to identify predictive markers for efficacy in every subtypes.

Targeted Therapy: Participants with druggable gene mutations will receive the corresponding molecular targeted drugs.

1. Participants with epidermal growth factor receptor (EGFR) gene mutation will receive Gefitinib, which inhibits a protein called EGFR that is thought to be a key factor in the development and progression of some cancers.
2. Participants with B-type Raf kinase (BRAF) gene mutations will receive Vemurafenib, which inhibits a protein called mitogen-activated or extracellular signal-regulated protein kinase kinase (MEK) that is thought to be a key factor in the development and progression of some cancers.
3. Participants with v-akt murine thymoma viral oncogene homologue 1 (AKT1) gene mutations will receive Celecoxib, which inhibits a protein called v-akt murine thymoma viral oncogene homologue (AKT) that is thought to be a key factor in the development and progression of some cancers.
4. Participants who have erythroblastic leukemia viral oncogene homolog 2 (ERBB2) gene mutation will receive Lapatinib, which inhibits some proteins that are thought to be key factors in the development and progression of some cancers.
5. Participants with PDGFRA/PDGFRB gene mutations will receive Sunitinib, which inhibits some proteins that are thought to be key factors in the development and progression of some cancers.
6. Participants with PIK3CA gene mutations will receive Everolimus, which inhibits a protein called AKT that is thought to be a key factor in the development and progression of some cancers.
7. Participants with DNA-repair gene defects will receive Olaparib, which inhibits poly ADP ribose polymerase (PARP).

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shimiao Zhu, MD,PhD; Phone Number: +86 137 5243 6539; Email: zhushimiao@tijmu.edu.cn

Study Locations

• China
  • Tianjin, China, 300211
    • Recruiting
    • Tianjin Medical Unversity Second Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Participants who have given consent form;
2. Patients with a confirmed diagnosis of mCRPC according to EAU 2018 guideline;
3. Serum testosterone must reach castration level: <50 ng per deciliter;
4. Participants with life expectancy of at least 6 months based on the Investigator's clinical judgment.

Exclusion Criteria:

1. Participants who are allergic to contrast medium;
2. Patients were excluded if they planned to receive additional concurrent anticancer therapies;
3. Patients doesn't sign an informed consent form.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Luminal type-1; Standard treatment	Drug: Luminal type-1; Goserelin (3.75mg, once every 4 weeks)+Docetaxel (75 mg/m2 on day 1 every 3 weeks)+Prednisone (5 mg, twice daily)
Experimental: Luminal type-2; Experimental treatment	Drug: Luminal type-2; Goserelin (3.75mg, once every 4 weeks)+Abiraterone (1000 mg, once daily)+Prednisone (5 mg, twice daily)
Active Comparator: Neuroendocrine type-1; Standard treatment	Drug: Neuroendocrine type-1; Goserelin (3.75mg, once every 4 weeks)+Docetaxel (75 mg/m2 on day 1 every 3 weeks)+Prednisone (5 mg, twice daily)
Experimental: Neuroendocrine type-2; Experimental treatment	Drug: Neuroendocrine type-2; Goserelin (3.75mg, once every 4 weeks)+Carboplatin (area under the curve 5 on day 1 every 3 weeks)+Docetaxel (75 mg/m2 on day 1 every 3 weeks)+Prednisone (5 mg, twice daily)
Active Comparator: Atypical type-1; Standard treatment	Drug: Atypical type-1; Goserelin (3.75mg, once every 4 weeks)+Docetaxel (75 mg/m2 on day 1 every 3 weeks)+Prednisone (5 mg, twice daily)
Experimental: Atypical type-2; Experimental treatment	Drug: Atypical type-2; Goserelin (3.75mg, once every 4 weeks)+Abiraterone (1000 mg, once daily)+ targeted therapy according to next Generation Sequencing (NGS)+ Prednisone (5 mg, twice daily), or Goserelin (3.75mg, once every 4 weeks)+Abiraterone+ Prednisone (5 mg, twice daily) if no druggable gene mutation detected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	OS was defined as the duration from the initiation of treatment to death of any cause	Up to 40 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA response rate	PSA response is defined as ≥ 50% decline in PSA level from baseline, maintained for≥ 4 weeks	Up to 40 months
PSA-Progression free survival (pPFS)	PSA progression was defined as an increase in the PSA level of 25% or more above the nadir (and by≥2 ng/ml), with confirmation of 4 or more weeks later	Up to 40 months
Radiographic progression free survival (rPFS)	rPFS was defined 1) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 criteria; or 2) as at least two new lesions on first post-treatment bone scan, with at least two additional lesions on the next bone scan	Up to 40 months

Collaborators and Investigators

• Sponsor: Tianjin Medical University Second Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Anticipated): August 1, 2022
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: October 3, 2018
• First Submitted That Met QC Criteria: October 3, 2018
• First Posted (Actual): October 4, 2018

Study Record Updates

• Last Update Posted (Actual): October 9, 2018
• Last Update Submitted That Met QC Criteria: October 4, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Chemotherapy; Metastatic Castration-resistant Prostate Cancer; Cancer Subtype; Target Therapy
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Hypnotics and Sedatives; GABA Modulators; GABA Agents; Anticonvulsants; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Phenobarbital
• Other Study ID Numbers: STAMP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No