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

Primary Purpose

Metastatic Castration Resistant Prostate Cancer

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

177Lu-PSMA-617

About this trial

This is an interventional treatment trial for Metastatic Castration Resistant Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

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
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

Exclusion Criteria:

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

Sites / Locations

David Geffen School of Medicine at UCLA
Excel Diagnostics and Nuclear Oncology Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

177Lu-PSMA-617 (6.0 GBq)

177Lu-PSMA-617 (7.4 GBq)

Arm Description

Repeated 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

Repeated 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

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

PSA Progression and Death Events

PSA progression was defined as: 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), 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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT03042312

First Posted

January 18, 2017

Last Updated

March 1, 2021

Sponsor

Endocyte

1. Study Identification

Unique Protocol Identification Number

NCT03042312

Brief Title

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

Acronym

RESIST-PC

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Terminated

Why Stopped

Recruitment was stopped before the target sample size was achieved.

Study Start Date

July 12, 2017 (Actual)

Primary Completion Date

January 15, 2020 (Actual)

Study Completion Date

January 15, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Endocyte

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Castration Resistant Prostate Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

71 (Actual)

8. Arms, Groups, and Interventions

Arm Title

177Lu-PSMA-617 (6.0 GBq)

Arm Type

Experimental

Arm Description

Repeated 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

Arm Title

177Lu-PSMA-617 (7.4 GBq)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

177Lu-PSMA-617

Other Intervention Name(s)

Lu177 RLT

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of Participants With Treatment Emergent Adverse Events

Description

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

Title

Number of Participants Achieving PSA Response at Week 12

Description

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

Time Frame

Week 12

Secondary Outcome Measure Information:

Title

Percent Change in PSA From Baseline to Week 12

Description

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

Time Frame

Week 12

Title

Maximum Percent Change in PSA Response

Description

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

Time Frame

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

Title

PSA Progression and Death Events

Description

Time Frame

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

Title

RECIST 1.1 Overall Response by Follow-up Assessment Visit

Description

Time Frame

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.

Title

RECIST 1.1 Disease Control Rate by Follow-up Assessment Visit

Description

Time Frame

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.

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 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 Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

David Geffen School of Medicine at UCLA

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

Excel Diagnostics and Nuclear Oncology Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77042

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34246328

Citation

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.

Results Reference

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

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