imPlementing ROutine Molecular Characterization in Patients With Metastatic Castration Resistant ProstaTe Cancer by NGS

Metastatic Prostate Cancer Clinical Trial

— PROMPT  

Official title:

imPlementing ROutine Molecular Characterization in Patients With Metastatic Castration-resistant ProsTate Cancer by Next Generation DNA Sequencing (PROMPT-study)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04746300
• Other study ID #: MOURO41 - PROMPT
• Secondary ID: NL68315.091.19
• Status: Recruiting
• Start date: February 4, 2020
• Est. completion date: February 2025

Study information

• Verified date: January 2021
• Source: Radboud University
• Contact: Niven Mehra, MD, PhD
• Phone: +312410354
• Email: niven.mehra[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The PROMPT study aims to routinely implement genomic pre-sorting of metastatic castration-resistant prostate cancer (mCRPC) patients for personalized treatment (e.g. immuno-, PARP inhibitors, or platinum-therapy). The investigators hypothesize that, by doing this early in the disease course (before exhausting standard of care options), it will improve treatment planning, patient outcome, quality of life, and reduce costs.

Description:

Prostate cancer is a major health problem leading to significant morbidity and mortality in men worldwide. Approved therapies for metastatic castration-resistant prostate cancer (mCRPC) include abiraterone and enzalutamide (targeting the androgen signaling pathway), radium-223 (bone targeting radionuclide therapy), and taxane chemotherapy. Controversy remains on optimal sequencing of available therapeutic agents, and these drugs are still commonly prescribed in a trial-and-error manner. Only a minority of patients receives the full benefit of the anticancer armamentarium, but all experience unnecessary side-effects, quality of life deterioration, and delay in onset to adequate life-prolonging treatment. In addition, the prescription of ineffective drugs and avoidable hospital admissions contribute to the financial burden of health care systems. In recent years, distinct molecular subsets of prostate cancer have been identified in mCRPC. These molecular defects may guide physicians in proper sequencing of medication and in predicting the individual response more accurately. In previous studies using next-generation sequencing (NGS) mCRPC patients could be grouped into clearly distinct molecular subtypes. Moreover, in these subtypes biomarkers associated with resistance to certain therapies, or biomarkers actually predictive for enhanced response were identified. In this study the investigators will introduce routine molecular characterization in participants with mCRPC as early as possible in their disease state. Participants will be screened before initiation of second-line treatment, since early identification will maximize clinical and financial benefit. Following screening, participants will be discussed in molecular tumor board and clinical meetings, and stratified to the agent they are most likely to respond to. Translational research is included to identify and validate additional predictive molecular biomarkers.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: February 2025
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male aged 18 or older with adenocarcinoma of the prostate defined by: Documented histopathology at diagnosis of prostate adenocarcinoma without evidence of predominant or primary neuroendocrine histology.

2. Patients with a metastatic tumor site accessible for image-guided biopsy and allowing research analyses for this trial (e.g. biomarker testing by genomic, proteomic or transcriptomic assessment). A waiver can be made for patients presenting with metastatic hormone-sensitive prostate cancer (mHSPC), and no easily accessible tumour for biopsy and suitable primary tissue available for NGS.

3. Castration-resistant state (defined as disease progressing despite [chemical] castration per PCWG3 criteria)

4. Progressive disease as either

• A rising PSA on minimum 2 serial consecutive measurements
• Radiographic soft tissue progression per RECIST1.1 or bone progression per PCWG3 criteria
• Clinical progression

5. At least one metastatic lesion present at baseline CT, MRI, 68Ga/18F-PSMA PET or bone scan

6. ECOG Performance status 0 to 2

7. Serum testosterone on castration level

8. Adequate renal function:

• MDRD-GFR = 30 ml/min/1.73m2

9. Adequate bone marrow function:

• Absolute neutrophil count (ANC) = 1.5 x 109/L
• Platelet count = 100 x109/L
• Hemoglobin (Hb) = 5.6 mmol/L

10. Adequate liver function:

• Total bilirubin level = 2 institutional upper limit of the normal (ULN)
• Aspartate aminotransferase (ASAT) = 3 x ULN (or = 5x ULN in case of known liver metastases)
• Alanine aminotransferase (ALAT) = 3 x ULN (or = 5x ULN in case of known liver metastases)

11. Estimated life expectancy > 12 months

12. Willing and able to comply to the research protocol

13. Signed, written informed consent

Exclusion Criteria:

1. Prior chemotherapy and androgen receptor inhibition therapy related to castration resistant prostate cancer (one line of chemotherapy or androgen receptor inhibition may be given in the hormone-sensitive setting)

2. Active malignancy other than prostate cancer, except for patients with basal or squamous skin cancer. A waiver may be obtained from the PI in cases where the active malignancy is indolent and believed not to reduce mortality.

3. Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI).

4. Concurrent illness, including severe infection that may jeopardize the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety

5. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse

6. Any condition which, in the opinion of the investigator, would preclude participation in this observational study.

Related Conditions & MeSH terms

• Metastatic Prostate Cancer
• Prostatic Neoplasms

Intervention

Procedure:
• Biopsy
A biopsy will be taken from metastatic tissue, which will be used for DNA sequencing
• Blood sample
Blood samples will be taken for additional translational research

Locations

Country	Name	City	State
Netherlands	Radboud UMC	Nijmegen	Gelderland

Sponsors (4)

Lead Sponsor	Collaborator
Radboud University	Paul Speth Foundation (NL), Radboud Oncology Fund (NL), VGZ health insurance (NL)

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Responsiveness ratio	Ratio of radiographic progression-free survival of personalized treatment or standard of care to the standard last line therapy (PFS-MPT-ratio vs PFS-SOC-ratio)	Throughout completion of study (estimated 5 years from start)
Secondary	Efficacy endpoint: ORR	Best objective response rate (ORR) per RECIST1.1 criteria	Throughout completion of study (estimated 5 years from start)
Secondary	Efficacy endpoint: rPFS	Radiographic progresssion free survival (per RECIST1.1)	Throughout completion of study (estimated 5 years from start)
Secondary	Efficacy endpoint: PSA response	PSA decline >50% at 12 weeks or later	Throughout completion of study (estimated 5 years from start)
Secondary	Efficacy endpoint: PSA-PFS	Time to PSA progression (per PCWG3 criteria)	Throughout completion of study (estimated 5 years from start)
Secondary	Efficacy endpoint: OS	Overall survival capped at 1 year	Throughout completion of study (estimated 5 years from start)
Secondary	Quality of life endpoint: EORTC-QLQ-30	Score of EORTC-QLQ-30 questionnaire	Throughout completion of study (estimated 5 years from start)
Secondary	Quality of life endpoint: EPIC-26	Score of EPIC-26 questionnaire	Throughout completion of study (estimated 5 years from start)
Secondary	Quality of life endpoint: EQ-5D-5L	Score of EQ-5D-5L questionnaire	Throughout completion of study (estimated 5 years from start)
Secondary	Quality of life endpoint: BIP-SF	Score of BIP-SF questionnaire	Throughout completion of study (estimated 5 years from start)
Secondary	Medical Resource Utilization (MRU); nr of lines	Averaged number of lines of standard care per year	At the end of year 1, year 2, year 3, and at completion of the study (estimated end of year 5)
Secondary	Medical Resource Utilization (MRU); costs	Averaged costs of standard care per year	At the end of year 1, year 2, year 3, and at completion of the study (estimated end of year 5)
Secondary	Medical Resource Utilization (MRU); treatment-related costs	Averaged costs of treatment-related resource utilization (e.g. admissions in ward or ICU) per admission and/or per duration	At the end of year 1, year 2, year 3, and at completion of the study (estimated end of year 5)