NEPC Study: An Exploratory Safety and Efficacy Study With PSMA, SSTR2 and GRPR Targeted Radioligand Therapy in Metastatic Neuroendocrine Prostate Cancer.

NCT ID: NCT06379217

Last Updated: 2026-01-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-29

Study Completion Date

2027-06-23

Brief Summary

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The purpose of this study is to evaluate the change in the expression of treatment targets on the surface of tumor cells (Prostate Specific Membrane Antigen (PSMA), Somatostatin Receptor 2 (SSTR2), and Gastrin Releasing Peptide Receptor (GRPR) between the baseline and following targeted radioligand therapy (RLT). Study will use radioligand imaging (RLI) to determine predominantly expressed target on the surface of tumor cells. Based on predominant expression of target, corresponding RLT targeting PSMA, SSTR2, or GRPR RLT will be given for up to 6 cycles every 6 weeks as intravenous (i.v.) injection in participants with metastatic neuroendocrine prostate cancer (mNEPC).

Study is planning to enroll approximately 20 participants in \[177Lu\]Lu-PSMA-617 treatment arm, approximately 3 participants in \[177Lu\]Lu-NeoB treatment arm, and approximately 13 participants in \[177Lu\]Lu-DOTA-TATE treatment arm.

Detailed Description

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The screening period for each participant includes imaging with 3 radioligand imaging (RLI) compounds to assess expression level of PSMA, SSTR2 and GRPR. Participants will be assigned to the radioligand treatment (RLT) corresponding to their predominantly expressed target based on blinded independent central review (BICR). During the treatment period, participants will receive up to 6 cycles of the assigned RLT, corresponding to a total dose of 44.4 GBq (+/-10%) for \[177Lu\]Lu-PSMA-617 or \[177Lu\]Lu-DOTA-TATE , and 55.5 GBq (+/-10%) for \[177Lu\]Lu-NeoB. No crossover to a different type of RLT is allowed.

At least six weeks after receiving the first cycle of RLT, participants must be scanned again with up to 3 RLIs but must be scanned, with at least with one RLI corresponding to the received RLT, which is recommended to be performed first. All post-baseline PET/CT scans should be performed using the same PET/CT imaging agent and same PET/CT camera, acquisition and reconstruction protocols as used for screening PET/CT for the participant.

The post-treatment follow-up period consists of a 42-days post EOT safety follow-up visit, efficacy, and survival follow-up until radiographic disease progression, death, lost to follow-up or withdrawal of consent, whichever occurs first.

The planned duration of treatment is up to 36 weeks for all treatment arms in this study, with treatment given every 6 weeks ±7 days. Participants may be discontinued from treatment earlier due to unacceptable toxicity or disease progression, and/or at the discretion of the Investigator or the participant.

Conditions

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Metastatic Neuroendocrine Prostate Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Participants will be assigned to a treatment arm based on their predominantly expressed target per PET images (based on central read):

* \[177Lu\]Lu-PSMA-617 will be assigned to those with predominant PSMA expression
* \[177Lu\]Lu-DOTA-TATE will be assigned to those with predominant SSTR2 expression
* \[177Lu\]Lu-NeoB will be assigned to those with predominant GRPR expression

In complex cases the local Investigator has the authority to make decisions on the most appropriate RLT assignment.

If the selected RLT assignment is to a treatment arm that has reached its maximum enrollment, the patient will not be able to receive the selected RLT and will not join the treatment phase.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PSMA-predominant NEPC

Group Type EXPERIMENTAL

[68Ga]Ga-PSMA-11

Intervention Type DRUG

\[68Ga\]Ga-PSMA-11 will be administered as a single intravenous dose of approximately 150 MBq (4 mCi) to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. Administered dose should not be lower than 111 MBq (3 mCi) or higher than 259 MBq (7 mCi)

[68Ga]GA-DOTA-TATE

Intervention Type DRUG

\[68Ga\]Ga-DOTA-TATE will be administered as a single intravenous dose to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. within a range of 100-200MBq (2.7-5.4 mCi)

[68Ga]Ga-NeoB

Intervention Type DRUG

\[68Ga\]Ga-NeoB will be administered as a single intravenous dose to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. within a range of 150-250 MBq (4.1-6.8 mCi).

[177Lu]Lu-PSMA-617

Intervention Type DRUG

\[177Lu\]Lu-PSMA-617 will be administered as an intravenous infusion at a dose of 7.4 GBq (200mCi) (+/- 10%), every 6 weeks for 6 cycles.

Gonadotropin-releasing hormone (GnRH) analogues

Intervention Type DRUG

Anatomical Therapeutic Chemical \[ATC\] code L02AE

GnRH antagonists

Intervention Type DRUG

abarelix, degarelix, or relugolix

SSTR2-predominant NEPC

Group Type EXPERIMENTAL

[68Ga]Ga-PSMA-11

Intervention Type DRUG

\[68Ga\]Ga-PSMA-11 will be administered as a single intravenous dose of approximately 150 MBq (4 mCi) to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. Administered dose should not be lower than 111 MBq (3 mCi) or higher than 259 MBq (7 mCi)

[68Ga]GA-DOTA-TATE

Intervention Type DRUG

\[68Ga\]Ga-DOTA-TATE will be administered as a single intravenous dose to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. within a range of 100-200MBq (2.7-5.4 mCi)

[68Ga]Ga-NeoB

Intervention Type DRUG

\[68Ga\]Ga-NeoB will be administered as a single intravenous dose to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. within a range of 150-250 MBq (4.1-6.8 mCi).

[177Lu]Lu-DOTA-TATE

Intervention Type DRUG

\[177Lu\]Lu-DOTA-TATE will be administered as an intravenous infusion at a dose of 7.4 GBq (200mCi) (+/- 10%) every 6 weeks for 6 cycles.

L-Lysine HCl-L-Arginine HCl, 2.5 %,

Intervention Type DRUG

sterile solution for infusion Lysine HCl-Arginine HCl, 2.5 % (1L)

Gonadotropin-releasing hormone (GnRH) analogues

Intervention Type DRUG

Anatomical Therapeutic Chemical \[ATC\] code L02AE

GnRH antagonists

Intervention Type DRUG

abarelix, degarelix, or relugolix

Antiemetics & antinauseants

Intervention Type DRUG

ATC code A04A

Metoclopramide

Intervention Type DRUG

ATC code A03FA01

GRPR-predominant NEPC

Group Type EXPERIMENTAL

[68Ga]Ga-PSMA-11

Intervention Type DRUG

\[68Ga\]Ga-PSMA-11 will be administered as a single intravenous dose of approximately 150 MBq (4 mCi) to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. Administered dose should not be lower than 111 MBq (3 mCi) or higher than 259 MBq (7 mCi)

[68Ga]GA-DOTA-TATE

Intervention Type DRUG

\[68Ga\]Ga-DOTA-TATE will be administered as a single intravenous dose to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. within a range of 100-200MBq (2.7-5.4 mCi)

[68Ga]Ga-NeoB

Intervention Type DRUG

\[68Ga\]Ga-NeoB will be administered as a single intravenous dose to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. within a range of 150-250 MBq (4.1-6.8 mCi).

[177Lu]Lu-NeoB

Intervention Type DRUG

\[177Lu\]Lu-NeoB will be administered as an intravenous infusion at a dose of 9.25 GBq (250mCi) every 6 weeks for 6 cycles

Gonadotropin-releasing hormone (GnRH) analogues

Intervention Type DRUG

Anatomical Therapeutic Chemical \[ATC\] code L02AE

GnRH antagonists

Intervention Type DRUG

abarelix, degarelix, or relugolix

Interventions

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[68Ga]Ga-PSMA-11

\[68Ga\]Ga-PSMA-11 will be administered as a single intravenous dose of approximately 150 MBq (4 mCi) to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. Administered dose should not be lower than 111 MBq (3 mCi) or higher than 259 MBq (7 mCi)

Intervention Type DRUG

[68Ga]GA-DOTA-TATE

\[68Ga\]Ga-DOTA-TATE will be administered as a single intravenous dose to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. within a range of 100-200MBq (2.7-5.4 mCi)

Intervention Type DRUG

[68Ga]Ga-NeoB

\[68Ga\]Ga-NeoB will be administered as a single intravenous dose to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. within a range of 150-250 MBq (4.1-6.8 mCi).

Intervention Type DRUG

[177Lu]Lu-PSMA-617

\[177Lu\]Lu-PSMA-617 will be administered as an intravenous infusion at a dose of 7.4 GBq (200mCi) (+/- 10%), every 6 weeks for 6 cycles.

Intervention Type DRUG

[177Lu]Lu-DOTA-TATE

\[177Lu\]Lu-DOTA-TATE will be administered as an intravenous infusion at a dose of 7.4 GBq (200mCi) (+/- 10%) every 6 weeks for 6 cycles.

Intervention Type DRUG

[177Lu]Lu-NeoB

\[177Lu\]Lu-NeoB will be administered as an intravenous infusion at a dose of 9.25 GBq (250mCi) every 6 weeks for 6 cycles

Intervention Type DRUG

L-Lysine HCl-L-Arginine HCl, 2.5 %,

sterile solution for infusion Lysine HCl-Arginine HCl, 2.5 % (1L)

Intervention Type DRUG

Gonadotropin-releasing hormone (GnRH) analogues

Anatomical Therapeutic Chemical \[ATC\] code L02AE

Intervention Type DRUG

GnRH antagonists

abarelix, degarelix, or relugolix

Intervention Type DRUG

Antiemetics & antinauseants

ATC code A04A

Intervention Type DRUG

Metoclopramide

ATC code A03FA01

Intervention Type DRUG

Other Intervention Names

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Gallium (68Ga) gozetotide Gallium (68Ga) DOTA-TATE Gallium (68Ga) NeoB Lutetium (177Lu) vipivotide tetraxetan Lutetium (177Lu) DOTA-TATE Lutetium (177Lu) NeoB Lysine HCl-Arginine HCl, 2.5 %

Eligibility Criteria

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Inclusion Criteria

* Participants must have metastatic prostate cancer with neuroendocrine differentiation as determined by at least one of the following:

1. Histologically small cell or neuroendocrine cancer from a primary prostate or metastatic biopsy confirmed by local laboratory.
2. Expression of NEPC markers (e.g., chromogranin or synaptophysin) in tumor tissue by IHC confirmed by local laboratory
3. Progression of visceral metastases in the absence of PSA progression
4. Serum chromogranin A \> 5x normal limit, or neuron-specific enolase \> 2x normal limit with control for proton-pump inhibitors (PPI) drugs among concomitant treatment
5. Prostate adenocarcinoma with molecular features of neuroendocrine differentiated cancer (e.g., 2 of the following 3: PTEN, TP53, or RB loss)
* PSMA and/or SSTR2 and/or GRPR PET-positive participants, with at least one measurable lesion per RECIST 1.1 with moderate target expression in at least one of the 3 PET/CT scans per BICR assessment
* Castrate level of serum/plasma testosterone (\< 50 ng/dl, or \< 1.7 nmol/L) for participants with adenocarcinoma component or stable testosterone level for participants with pure neuroendocrine carcinoma
* Recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapy
* Participant has adequate bone marrow and organ function (as assessed by central laboratory for eligibility)
* ECOG status =\< 2

Exclusion Criteria

* Previous treatment with any of the following within 6 months prior to Screening: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation
* Previous PSMA, SSTR2, or GRPR targeted radioligand therapy
* Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy or investigational therapy
* History of CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity
* Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
* History or current diagnosis of ECG abnormalities indicating significant risk of safety for study participants
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Stanford University

Palo Alto, California, United States

Site Status RECRUITING

Nebraska Cancer Specialists

Omaha, Nebraska, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Ctr

New York, New York, United States

Site Status RECRUITING

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status RECRUITING

Novartis Investigative Site

Lille, , France

Site Status WITHDRAWN

Novartis Investigative Site

Nantes, , France

Site Status ACTIVE_NOT_RECRUITING

Novartis Investigative Site

München, , Germany

Site Status ACTIVE_NOT_RECRUITING

Novartis Investigative Site

Rostock, , Germany

Site Status ACTIVE_NOT_RECRUITING

Novartis Investigative Site

Meldola, FC, Italy

Site Status RECRUITING

Novartis Investigative Site

Reggio Emilia, RE, Italy

Site Status WITHDRAWN

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, Spain

Site Status RECRUITING

Novartis Investigative Site

Madrid, , Spain

Site Status RECRUITING

Novartis Investigative Site

Sutton, Surrey, United Kingdom

Site Status RECRUITING

Novartis Investigative Site

London, , United Kingdom

Site Status RECRUITING

Countries

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United States France Germany Italy Spain United Kingdom

Central Contacts

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Novartis Pharmaceuticals

Role: CONTACT

1-888-669-6682

Novartis Pharmaceuticals

Role: CONTACT

+41613241111

Facility Contacts

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Tiffany Chen

Role: primary

Marlene Bridwell

Role: primary

402-691-6972

Abirame Guruparan

Role: primary

+1 646 422 4379

Patrick Panlasigui

Role: primary

206-288-2056

Other Identifiers

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2023-505655-43

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CAAA617H12101

Identifier Type: -

Identifier Source: org_study_id

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