Trial Title:
NEPC Study: An Exploratory Safety and Efficacy Study With PSMA, SSTR2 and GRPR Targeted Radioligand Therapy in Metastatic Neuroendocrine Prostate Cancer.
NCT ID:
NCT06379217
Condition:
Metastatic Neuroendocrine Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Metoclopramide
Antiemetics
Hormones
Prolactin Release-Inhibiting Factors
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
Gallium 68 PSMA-11
Lutetium Lu 177 dotatate
Conditions: Keywords:
[68Ga]Ga-PSMA-11
[177Lu]Lu-PSMA-617
[68Ga]Ga-DOTA-TATE
[177Lu]Lu-DOTA-TATE
[68Ga]Ga-NeoB
[177Lu]Lu-NeoB
Neuroendocrine prostate cancer (NEPC)
Metastatic Neuroendocrine Prostate Cancer (mNEPC)
Radioligand Imaging (RLI)
Radioligand Therapy (RLT)
Prostate-specific membrane antigen (PSMA)
Somatostatin Receptor 2 (SSTR2)
Gastrin Releasing Peptide Receptor (GRPR)
Phase 1
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
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
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
[68Ga]Ga-PSMA-11
Description:
[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 approximately 7 weeks after
last RLT dose. Administered dose should not be lower than 111 MBq (3 mCi) or higher than
259 MBq (7 mCi)
Arm group label:
GRPR-predominant NEPC
Arm group label:
PSMA-predominant NEPC
Arm group label:
SSTR2-predominant NEPC
Other name:
Gallium (68Ga) gozetotide
Intervention type:
Drug
Intervention name:
[68Ga]GA-DOTA-TATE
Description:
[68Ga]Ga-DOTA-TATE will be administered as a single intravenous dose to be administered
during baseline imaging and approximately 7 weeks after last RLT dose, within a range of
100-200MBq (2.7-5.4 mCi)
Arm group label:
GRPR-predominant NEPC
Arm group label:
PSMA-predominant NEPC
Arm group label:
SSTR2-predominant NEPC
Other name:
Gallium (68Ga) DOTA-TATE
Intervention type:
Drug
Intervention name:
[68Ga]Ga-NeoB
Description:
[68Ga]Ga-NeoB will be administered as a single intravenous dose to be administered during
baseline imaging and approximately 7 weeks after last RLT dose.within a range of 150-250
MBq (4.1-6.8 mCi).
Arm group label:
GRPR-predominant NEPC
Arm group label:
PSMA-predominant NEPC
Arm group label:
SSTR2-predominant NEPC
Other name:
Gallium NeoB
Intervention type:
Drug
Intervention name:
[177Lu]Lu-PSMA-617
Description:
[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.
Arm group label:
PSMA-predominant NEPC
Other name:
Lutetium (177Lu) vipivotide tetraxetan
Intervention type:
Drug
Intervention name:
[177Lu]Lu-DOTA-TATE
Description:
[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.
Arm group label:
SSTR2-predominant NEPC
Other name:
Lutetium (177Lu) DOTA-TATE
Intervention type:
Drug
Intervention name:
[177Lu]Lu-NeoB
Description:
[177Lu]Lu-NeoB will be administered as an intravenous infusion at a dose of 9.25 GBq
(250mCi) every 6 weeks for 6 cycles
Arm group label:
GRPR-predominant NEPC
Other name:
Lutetium NeoB
Intervention type:
Drug
Intervention name:
L-Lysine HCl-L-Arginine HCl, 2.5 %,
Description:
sterile solution for infusion Lysine HCl-Arginine HCl, 2.5 % (1L)
Arm group label:
SSTR2-predominant NEPC
Other name:
Lysine HCl-Arginine HCl, 2.5 %
Intervention type:
Drug
Intervention name:
Gonadotropin-releasing hormone (GnRH) analogues
Description:
Anatomical Therapeutic Chemical [ATC] code L02AE
Arm group label:
GRPR-predominant NEPC
Arm group label:
PSMA-predominant NEPC
Arm group label:
SSTR2-predominant NEPC
Intervention type:
Drug
Intervention name:
GnRH antagonists
Description:
abarelix, degarelix, or relugolix
Arm group label:
GRPR-predominant NEPC
Arm group label:
PSMA-predominant NEPC
Arm group label:
SSTR2-predominant NEPC
Intervention type:
Drug
Intervention name:
Antiemetics & antinauseants
Description:
ATC code A04A
Arm group label:
SSTR2-predominant NEPC
Intervention type:
Drug
Intervention name:
Metoclopramide
Description:
ATC code A03FA01
Arm group label:
SSTR2-predominant NEPC
Summary:
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 start and after the completion of 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).
Detailed description:
The screening period for each subject 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 end of treatment (EoT) with RLT, participants will be scanned again with the 3 RLIs.
All EoT PET/CT scans should be performed using the 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
and long-term 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. 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.
Criteria for eligibility:
Criteria:
Key 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 scans
- 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
Key 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
Other protocol-defined inclusion/exclusion criteria may apply.
Gender:
Male
Gender based:
Yes
Gender description:
Participants must have metastatic prostate cancer
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Nebraska Cancer Specialists
Address:
City:
Omaha
Zip:
68130
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jena Depue
Phone:
402-691-6972
Email:
jdepue@nebraskacancer.com
Investigator:
Last name:
Samuel Mehr
Email:
Principal Investigator
Facility:
Name:
Novartis Investigative Site
Address:
City:
Lille
Zip:
59037
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Nantes Cedex 1
Zip:
44093
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Hospitalet de LLobregat
Zip:
08907
Country:
Spain
Status:
Recruiting
Start date:
July 29, 2024
Completion date:
June 22, 2027
Lead sponsor:
Agency:
Novartis Pharmaceuticals
Agency class:
Industry
Source:
Novartis
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06379217
