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Metastatic Castration Resistant Prostate CancerPhase 2RESIST-PCNCT03042312

Lutetium-177 (Lu177) Prostate-Specific Antigen (PSMA)-Directed EndoRadiotherapy

A Phase 2 study testing 177Lu-PSMA-617 in people with Metastatic Castration Resistant Prostate Cancer, run by Endocyte at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This was an open-label, multicenter, prospective trial to assess safety and efficacy of 177Lu-PSMA-617 in patients with metastatic castration resistant prostate cancer. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
177Lu-PSMA-617
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
71 participants
Where
2 sitesUnited States
Study dates
12 Jul 2017to 15 Jan 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Prostate cancer proven by histopathology
  • Unresectable metastases
  • Progressive disease, both docetaxel naive and docetaxel treated.
  • Castration resistant disease with confirmed testosterone level ≤50 ng/ml under prior androgen deprivation therapy (ADT)
  • Positive 68Ga-PSMA-11 PET/CT (positron emission computed tomography ) or diagnostic 177Lu-PSMA-617 scintigraphy
  • ECOG 0-2
Show all 9Show fewer
  • Sufficient bone marrow capacity as defined by WBC (white blood cell ) ≥2.500/μl, PLT (platelet) count ≥100.000/μl, Hb≥9.9 g/dl and ANC≥1500 mm3 for the first cycle and WBC≥2.000/ μl,PLT count ≥75.000/μl, Hb≥8.9 g/dl and ANC≥1000 mm3 for the subsequent cycles
  • Signing of the Informed Consent Form
  • Patients enrolling in this trail should have received either Enzalutamide or Abiraterone

Who cannot join

  • Less than 6 weeks since last myelosuppressive therapy (including Docetaxel, Cabazitaxel, 223Ra, 153Sm) or other radionuclide therapy.
  • Glomerular Filtration Rate (GFR) <40 ml/min
  • Serum creatinine > 1.5 ULN
  • AST and ALT>5xULN
  • Urinary tract obstruction or marked hydronephrosis
  • Diffuse bone marrow involvement confirmed by super-scans

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Excel Diagnostics and Nuclear Oncology Center

    Houston, Texas, 77042

  • David Geffen School of Medicine at UCLA

    Los Angeles, California, 90095

Other trials in United States

About this study

Official title: PSMA-directed endoRadiothErapy of Castration-reSISTant Prostate Cancer (RESIST-PC). A Phase II Clinical Trial

This was an open-label, multicenter, prospective trial to assess safety and efficacy of 177Lu-PSMA-617 in patients with metastatic castration resistant prostate cancer.

Read the detailed description

Upon inclusion patients were randomized in a 1:1 ratio into two treatment doses. Radioligand therapy (RLT) were performed by repeated intravenous (i.v.) injection of 6.0 gigabecquerel (GBq) (+/- 10%) or 7.4 GBq (+/- 10%) 177Lu-PSMA-617 every 8+/- 1 weeks until reaching four cycles or threshold maximum dose to the kidneys of 23 Gray (Gy). All doses after labeling were presented in buffered solution for i.v. injection.

In the initial plan for the study design a total of 200 patients with histologically proven prostate cancer and metastatic castration-resistant prostate cancer (mCRPC) were to be enrolled, however due to early stopping of enrollment only 71 patients were enrolled at time of data base lock. Each patient underwent a screening visit within 14 days prior to receiving study drug. Treatment was continued until either of the following conditions applied:

  • Prostate-specific antigen (PSA)/radiographic progression at >= 12 weeks
  • Completion of four RLT cycles
  • 23 Gy kidney dose would be exceeded by the next cycle as estimated by dosimetry
  • Patient withdrawal (e.g. appearance of intolerable adverse events).
Being tested
177Lu-PSMA-617

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 177Lu-PSMA-617Drug

    Also called Lu177 RLT

    Lutetium (177Lu) -DOTA (1,4,7,10-tetra-azacyclododecane-N,N',N'',N'''-tetraacetic acid )-PSMA has three components: PSMA is the targeting vector , DOTA (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid) is a radiometal chelator and a linking group, and 177Lu is the beta emitter that upon internalization delivers radiation to the nucleus of tumor cells to cause DNA damage. The targeting vector utilizes glu-urea-lys sequence which is an inhibitor capable of binding to the domain of PSMA. These components have been previously used in human subjects and in medical research.

Study groups in NCT03042312
Study groupRoleWhat they receive
177Lu-PSMA-617 (6.0 GBq)ExperimentalRepeated i.v. application of 6.0 GBq (gigabequerel)(+/- 10%, arm 1) every 8+/- 1 weeks; RLT until reaching four cycles or threshold maximum dose to the kidneys of 23 Gy as determined by dosimetry
Receives: Drug: 177Lu-PSMA-617
177Lu-PSMA-617 (7.4 GBq)ExperimentalRepeated i.v. application of 7.4 GBq (gigabequerel)(+/- 10%, arm 2) of drug every 8+/- 1 weeks; RLT until reaching four cycles or threshold maximum dose to the kidneys of 23 Gy as determined by dosimetry
Receives: Drug: 177Lu-PSMA-617

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Treatment Emergent Adverse Events

    Treatment-emergent adverse events (TEAEs) were collected from first dosing up to last follow-up visit or until the event has resolved to baseline grade or better or the event was assessed stable by the investigator or the patient was lost to follow-up or withdrew consent. The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis performed.

    Measured: From first dosing (Day 0) up to last follow-up visit or until the event has resolved to baseline grade or better or the event was assessed stable by the investigator or the patient was lost to follow-up or withdrew consent, up to 24 months

  2. Number of Participants Achieving PSA Response at Week 12

    PSA response was defined as the proportion of patients who had a >= 50% decrease in PSA from Baseline at Week 12.

    Measured: Week 12

Secondary outcomes (8)

  1. Percent Change in PSA From Baseline to Week 12

    Percent change in PSA from Baseline to Week 12 was reported for participants who had a baseline and a week 12 valid assessments.

    Measured: Week 12

  2. Maximum Percent Change in PSA Response

    Maximal baseline to follow-up PSA decline, at any time during or after therapy was evaluated in both treatment groups.

    Measured: Every 6 weeks during the treatment and every 3 (+/- 1) months after last treatment until reaching endpoint or 24 months after the first treatment

  3. PSA Progression and Death Events

    PSA progression was defined as:

    1. For patients with PSA decline: PSA progression was defined as the date that a >= 25% increase in PSA and an absolute increase of 2 ng/mL or more from the nadir was documented and confirmed by a second consecutive value obtained 3 or more weeks later. Rises in PSA within the first 12 weeks were ignored (PCWG3 Guidance),
    2. For patients without PSA decline: PSA progression was defined as a >= 25% increase from the baseline value along with an increase in absolute value of 2 ng/mL or more after 12 weeks of treatment.

    Measured: Date of randomization to the date of first documented PSA progression or death, whichever occurs first, reported between day of first patient randomized up to 24 months after the first treatment

  4. RECIST 1.1 Overall Response by Follow-up Assessment Visit

    For each follow-up imaging assessment by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for target, non-target, and new lesions assessed by CT or MRI: the number of participants with an overall response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD).

    The timing of follow-up imaging assessments varied depending on how many RLT cycles a participant received. Therefore, regardless of when the imaging assessments occurred, each participant's first follow-up imaging was combined as Follow-up 1, each participant's second follow-up imaging was combined as Follow-up 2, each participant's third follow-up imaging was combined as Follow-up 3, and each participant's fourth follow-up imaging was combined as Follow-up 4.

    Measured: Before 3rd radioligand therapy (RLT) cycle, and then every 3 (+/- 1) months after last treatment dose until disease progression or 24 months after the first treatment dose.

  5. RECIST 1.1 Disease Control Rate by Follow-up Assessment Visit

    The proportion of participants with an overall response of Complete Response (CR), Partial Response (PR) and Stable Disease (SD) was reported using investigator assessments per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for target, non-target, and new lesions assessed by CT or MRI.

    The timing of follow-up imaging assessments varied depending on how many RLT cycles a participant received. Therefore, regardless of when the imaging assessments occurred, each participant's first follow-up imaging was combined as Follow-up 1, each participant's second follow-up imaging was combined as Follow-up 2, each participant's third follow-up imaging was combined as Follow-up 3, and each participant's fourth follow-up imaging was combined as Follow-up 4.

    Measured: Before 3rd radioligand therapy (RLT) cycle, and then every 3 (+/- 1) months after last treatment dose until disease progression or 24 months after the first treatment dose.

  6. Prostate Cancer Working Group 3 (PCWG3) Bone Scan Clinical Impression by Visit

    Investigator's assessed bone metastases using the Prostate Cancer Working Group 3 (PCWG3) criteria; new lesions had to be confirmed on a second scan (2+2 rule). The investigator documented their clinical impression of each PCWG3 assessment as Improved, Stable or Progression. The number of participants with a clinical impression of Improved, Stable or Progression according to PCWG3 using investigators assessments was reported by visit.

    Measured: Screening, Week 8, Week 10, Week 16, Week 18, Week 22, Week 24, Follow-up Week 4, Follow-up Week 6, Follow-up Week 8

  7. Change From Baseline in Expanded Prostate Cancer Index Composite Short Form (EPIC-26)

    The Expanded Prostate Cancer Index-Composite (EPIC) is a well-established patient-reported outcome (PRO) questionnaire developed to monitor health-related quality of life outcomes among prostate cancer. The 26-item version of EPIC, also known as EPIC Short Form or EPIC-26, contains 26 items and 5 domains: Urinary Incontinence (Items 1-4), Urinary Irritative/Obstructive (Items 5-8), Bowel (Items 10-15), Sexual (Items 16-21), and Hormonal (Items 22-26). Response options for each EPIC item form a Likert scale, and multi-item scale scores are transformed linearly to a 0 to 100 scale for each domain, with higher scores representing better health-related quality of life.

    Measured: Baseline, Month 3, Month 6, Follow-up Month 3

  8. Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status

    The Eastern Cooperative Oncology Group Performance Status (ECOG PS) score classifies participants according to their functional impairment, with scores ranging from 0 (fully active) to 5 (dead). ECOG PS: 0 = fully active, able to carry on all pre-disease performance without restriction; 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work; 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3 = capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5 = dead.

    Measured: Baseline, Treatment Visit 1, Treatment Visit 2, Treatment Visit 3, Treatment Visit 4, Follow-up Month 3, Follow-up Month 12, Follow-up Month 15

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Feb 2017 (estimated)
  2. Study start12 Jul 2017
  3. Primary completion15 Jan 2020
  4. Study completion15 Jan 2020

Why it stopped: Recruitment was stopped before the target sample size was achieved.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
71 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03042312
Sponsor's protocol ID
PSMA-617-02
Other IDs
133661
Acronym
RESIST-PC
Status last verified
Mar 2021
First submitted
18 Jan 2017
Last updated
24 Mar 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Gafita A, Calais J, Grogan TR, Hadaschik B, Wang H, Weber M, Sandhu S, Kratochwil C, Esfandiari R, Tauber R, Zeldin A, Rathke H, Armstrong WR, Robertson A, Thin P, D'Alessandria C, Rettig MB, Delpassand ES, Haberkorn U, Elashoff D, Herrmann K, Czernin J, Hofman MS, Fendler WP, Eiber M. Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study. Lancet Oncol. 2021 Aug;22(8):1115-1125. doi: 10.1016/S1470-2045(21)00274-6. Epub 2021 Jul 8.

    PubMed 34246328

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 177Lu-PSMA-617 in people with Metastatic Castration Resistant Prostate Cancer, run by Endocyte at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment Emergent Adverse Events (time frame: From first dosing (Day 0) up to last follow-up visit or until the event has resolved to baseline grade or better or the event was assessed stable by the investigator or the patient was lost to follow-up or withdrew consent, up to 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03042312, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2021.

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