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

• ClinicalTrials.gov Identifier: NCT04746300
• Recruitment Status: Recruiting
• First Posted: February 9, 2021
• Last Update Posted: February 9, 2021
• Sponsor: Radboud University Medical Center
• Collaborators: VGZ health insurance (NL); Paul Speth Foundation (NL); Radboud Oncology Fund (NL)
• Information provided by (Responsible Party): Radboud University Medical Center

Tracking Information

• First Submitted Date: January 28, 2021
• First Posted Date: February 9, 2021
• Last Update Posted Date: February 9, 2021
• Actual Study Start Date: February 4, 2020
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 5, 2021)

Responsiveness ratio [ Time Frame: Throughout completion of study (estimated 5 years from start) ]

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)

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: February 5, 2021)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: imPlementing ROutine Molecular Characterization in Patients With Metastatic Castration Resistant ProstaTe Cancer by NGS
• Official Title: imPlementing ROutine Molecular Characterization in Patients With Metastatic Castration-resistant ProsTate Cancer by Next Generation DNA Sequencing (PROMPT-study)
• Brief 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.

Detailed 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.

• Study Type: Observational [Patient Registry]
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: 3 Years

Biospecimen

Retention:   Samples With DNA

Description:

CT-guided biopsies from lymph node, soft tissue, viscera and bone are collected. Blood and urine specimens are collected.

• Sampling Method: Probability Sample
• Study Population: A total of 600 patients with metastatic castration-resistant prostate cancer with clinical, radiographic or biochemical disease progression may be included in this study. The expected number of patients eligible for the protocol is well above 200 patients per year, including referrals from regional/community hospitals.
• Condition: Metastatic Prostate Cancer

Intervention

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

Study Groups/Cohorts

• Group 1: no sequencing
  Participants in this group, for which DNA sequencing could not be reported due to a variety of (quality/technical) reasons, will be treated with standard of care therapy. This group is therefore comparable to patients treated outside the Radboudumc.
  Interventions:

  • Procedure: Biopsy
  • Procedure: Blood sample
• Group 2: no druggable aberration
  Participants in this group received a DNA sequencing report identifying no biomarkers to which a logical treatment option can be connected. These participants will also receive standard of care therapy.
  Interventions:

  • Procedure: Biopsy
  • Procedure: Blood sample
• Group 3: allocated to personalized treatment
  Participants in this group received a DNA sequencing report which identified presence of a biomarker allowing the participant to be treated with a personalized therapy. This therapy could range from immunotherapy, or PARP inhibitors, to other medication.
  Interventions:

  • Procedure: Biopsy
  • Procedure: Blood sample

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 5, 2021): 400
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2025
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Niven Mehra, MD, PhD; +312410354; niven.mehra@radboudumc.nl

Contact: Iris Kloots, MD; iris.kloots@radboudumc.nl

• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT04746300
• Other Study ID Numbers: MOURO41 - PROMPT; NL68315.091.19 ( Registry Identifier: ABR registry )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Radboud University Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Radboud University Medical Center
• Original Study Sponsor: Same as current

Collaborators

• VGZ health insurance (NL)
• Paul Speth Foundation (NL)
• Radboud Oncology Fund (NL)

• Investigators: Not Provided
• PRS Account: Radboud University Medical Center
• Verification Date: January 2021