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Detection of Clinically Significant Prostate Cancer With 18F-DCFPyL PET/MR (PSMA-DOCS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03149861
Recruitment Status : Active, not recruiting
First Posted : May 11, 2017
Last Update Posted : August 13, 2020
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

Tracking Information
First Submitted Date  ICMJE May 1, 2017
First Posted Date  ICMJE May 11, 2017
Last Update Posted Date August 13, 2020
Actual Study Start Date  ICMJE June 8, 2017
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 9, 2017)
Rate of clinically significant prostate cancer (csPCa) detected in the study population by 18F-DCFPyL-PET/mpMR as compared to mpMR alone [ Time Frame: Through study completion, up to 2 years ]
We will compare rates of csPCa detection in 18F-DCFPyL-PET, mpMR and fused 18F-DCFPyL-PET/mpMR, with histopathology obtained at targeted fused US-PET/MR biopsy as the standard of reference
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2017)
  • Change in eligibility for focal therapy according to each modality [ Time Frame: Through study completion, up to 2 years ]
    We will document the proportion of patients who meet eligibility criteria for focal therapy, according to each modality (mpMR, 18F-DCFPyL PET and 18F-DCFPyL PET/MR), as determined in consensus between a radiologist and urologist. The change in proportions of eligible patients, according to each modality, will be reported
  • Correlation of tumor grade to PSMA expression on PET (SUV). [ Time Frame: Through study completion, up to 2 years ]
    Correlation of tumor grade to PSMA expression on PET (SUV).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Detection of Clinically Significant Prostate Cancer With 18F-DCFPyL PET/MR
Official Title  ICMJE Detection of Clinically Significant Prostate Cancer With 18F-DCFPyL PET/MR
Brief Summary

Background:

Currently, patients suspected of having prostate cancer undergo ultrasound-guided systematic biopsies of the prostate. However, up to a quarter of clinically significant tumors, which may pose a risk to patient's well-being, may be missed on random biopsies. MRI enables detection of further tumors in this patient population, but also has limited accuracy.

Study hypothesis:

We hypothesize that hybrid PET-MRI, a novel scanner which incorporates MRI with molecular imaging will improve the detection rate of clinically significant tumors.

Study design:

In this prospective trial, we will recruit 57 men who are suspected of having prostate cancer but have had negative systematic biopsies, who have been diagnosed with low-risk disease but have clinically signs of more aggressive tumor or who have a focal tumor detected and are candidates for minimally-invasive tumor ablation (=tumor destruction with laser or ultrasound waves), in whom it is crucial to exclude other tumor sites.

All patients will undergo PET/MRI after injection of a radiopharmaceutical called "18F-DCFPyL". This is a radioactive probe which has been shown in preliminary studies to be sensitive and specific for detection of prostate cancer.

All lesions detected on PET/MRI will undergo biopsy under ultrasound using fused PET/MRI and ultrasound images for guidance, and compared to histopathology. The primary outcome measure in this study is the proportion of clinically significant prostate cancers that are detected with PET/MRI compared to MRI alone. Improved detection of clinically significant prostate cancer may enable a tailored, personalized therapeutic approach, decreasing morbidity and potentially improving overall patient outcome.

Detailed Description

Prostate cancer overview:

Prostate cancer (PCa) is the 3rd leading cause of death from cancer in men and constitutes almost 1/4 of all new cancer cancers in men. Although PCa is prevalent, the risk of clinical or fatal PCa in a 50 year old man is estimated at only 10% and 3%, respectively Currently, over 2/3 of men diagnosed with PCa are diagnosed with organ confined, low risk disease (PSA < 10 ng/ml, Gleason score (=GS) 3+3, cT1c). Management is depending on tumor grade, size and stage and clinical parameters (e.g. life expectancy) and may range from active surveillance to radical therapy including definitive whole gland treatment (radical prostatectomy (RP), or radiotherapy). Although radical whole gland therapy is effective from an oncological standpoint, it may be associated with significant side effects. A more conservative approach in select patients may be enrollment in an active surveillance program. The concept behind this approach is that small volume, low grade PCa may have an indolent course and may not progress to biological significance in the absence of treatment in the patient's lifetime.

Conventional workup of patients with clinical suspicion of PCa:

Transrectal Ultrasound (TRUS)-guided biopsies: Current workup of patients with clinical suspicion of PCa includes TRUS-guided systematic biopsies. These are associated with a relatively high false negative rate, especially for areas difficult to access for biopsy, with csPCa missed in approximately 1 of 4 patients. Furthermore, there is only ˜50% correlation between biopsy obtained GS and final pathology at RP, with upgrading in more than 1 in 3 cases. This may lead to inaccurate risk stratification and inappropriate selection of therapy.

Role of multiparametric-MR & MR-Ultrasound Fusion Biopsy:

In recent years, multiparametric MR (mpMR) has been incorporated in the workup of patients with suspected PCa. T2- weighted imaging (T2WI) in combination with diffusion-weighted imaging (DWI) and dynamic contrast enhanced (DCE)-MR have shown promise in the detection, local staging and risk stratification of PCa, with a reported sensitivity and specificity of 0.74 & 0.88, respectively. Prostate MR is interpreted using a 5-point scoring scale (PI-RADS - Prostate Imaging and Reporting Archiving Data System), with an overall sensitivity & specificity of 77.0% & 71.4%, respectively, for detection of csPCa using PI-RADS-v2. Using MR-US fusion targeted biopsy for mpMR detected lesions improves detection of csPCa compared to standard biopsy (median: 9.1%) and improves correlation of biopsy-derived and surgical tumor grade.

Focal ablation therapy:

In recent years, trials have evaluated various focal ablative therapies (FT) as alternative management for select patients with low/ intermediate risk, organ-confined disease. FT for PCa involves varying degrees of predefined subtotal glandular ablation using a myriad of ablative energy sources e.g high intensity focused ultrasound (HIFU), or laser ablation. The common aim of all of these methods is curative-intent tumor ablation while minimizing morbidity, thereby potentially providing the best balance between oncologic control and side effects of radical therapy. FT relies on the notion that the index lesion can be identified by mpMRI, and localized for intervention. Although no long term data exists on the safety and oncologic outcome of FT, FT appears well-tolerated and associated with significantly less morbidity than whole-gland treatment. At our institution, in-bore focal laser ablation program (MRgFLT) allows patients with a single site of csPCa to be treated while the in-bore HIFU program allows inclusion of patients with up to 2 sites of csPCa confirmed on MR-TRUS fusion biopsy.

One of the main risks with a strategy of FT in PCa is selection failure. Although data is scarce, residual or unrecognized cancer was detected on follow-up biopsy in 22-50% of patients from two separate small series, including cancers in portions of the prostate not appreciated prior to intervention. Although it is uncertain how many of these are csPCa, this highlights the potential limitations of current workup algorithms for patients considered for FT. As only recognized index tumor site is targeted, detection of any further site of csPCa is paramount for appropriate patient selection and therapy success.

Molecular imaging in PCa:

There are shortcomings of current workup of patients with clinical suspicion of PCa, including significant false negative rate of TRUS-biopsies and mpMR. At least 1 in 5 patients in active surveillance program thought to have low-risk disease based on biopsies, turns out to have unfavorable features on surgical pathology. As specific patient management is based on accurate risk stratification, there is a clinical need for further tools to improve identification and characterization of csPCa. There has been increasing interest in molecular imaging in PCa in recent years. The most common radiopharmaceuticals used include choline (11C-Choline/ 18F-Fluorocholine) and 68Ga-PSMA.

PSMA, a type II transmembrane protein, is expressed in normal prostate epithelium and highly expressed in ~90% primary PCa and metastases. 68Ga-PSMA-HBED-CC, the most common PSMA PET radiopharmaceutical assessed to date, has shown high sensitivity in detecting recurrent disease. Recently developed 18F-labelled PSMA compounds (e.g. 18F-DCFPyL) offer several technical advantages over 68Ga including high imaging statistic and higher image resolution. Initial preclinical studies have shown favorable tissue binding and the first clinical investigation in 9 patients has shown very high levels of uptake in primary tumors and metastases with further pilot data suggesting additional metastases identified in >20% of patients compared to 68Ga-PSMA.

Recently introduced hybrid PET/MR scanners allow simultaneous acquisition of MR & PET data, incorporation the advantages of MR and molecular imaging. Emerging data is showing PET/MR to be potentially robust for assessment of oncology indications, particularly those that are better addressed with MR such as PCa. A recently published trial on 68Ga-PSMA PET/MR in intermediate-high risk patients has shown that mpMR, PET and PET/MR had a sensitivity of 66%, 92% and 98%, respectively in localizing Pca. PSMA-PET may also help characterize equivocal lesions on mpMR (PI-RAD v.2 score 3) and may facilitate targeted fusion biopsies of lesions not seen on MR.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Neoplasm, Prostate
Intervention  ICMJE
  • Procedure: PET/MR-ultrasound guided Fusion biopsy
    All focal lesion with PI-RADS >=3 on MR or with DCFPyL uptake on PET will undergo a focal fusion biopsy
  • Procedure: Systemic TRUS guided biopsy
    Transrectal ultrasound guided systemic prostate biopsy
Study Arms  ICMJE
  • Experimental: No focal biopsy needed
    Patients in which PET/MR have found no focal findings, will undergo a systemic biopsy as per standard of care, without specific cores for study purposes (Systemic TRUS guided biopsy)
    Intervention: Procedure: Systemic TRUS guided biopsy
  • Experimental: Focal biopsy
    Patients with a suspicious focal finding on PET/MR, will undergo systemic+focal or focal fusion biopsy (PET/MR-ultrasound guided Fusion biopsy)
    Intervention: Procedure: PET/MR-ultrasound guided Fusion biopsy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 12, 2020)
56
Original Estimated Enrollment  ICMJE
 (submitted: May 9, 2017)
57
Estimated Study Completion Date  ICMJE June 30, 2021
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients accrued will fit any of the following criteria:

    1. Clinical suspicion of PCa with negative TRUS-guided biopsy or clinically discordant low-risk PCa (suspicion of more extensive/aggressive disease).
    2. Potential candidates for FT (as per institutional guidelines).

Exclusion Criteria:

Patients will be ineligible to participate in this study if they meet any of the following criteria:

  1. Contraindication for MR as per current institutional guidelines.
  2. Contraindication for Gadolinium injection as per current institutional guidelines.
  3. Inability to lie supine for at least 60 minutes.
  4. Prostate biopsy <8 weeks prior to planned PET-MR.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Gender Eligibility Description: Prostate cancer study
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03149861
Other Study ID Numbers  ICMJE CAPCR ID:17-5295
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  ICMJE
Plan to Share IPD: No
Responsible Party University Health Network, Toronto
Study Sponsor  ICMJE University Health Network, Toronto
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University Health Network, Toronto
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP