Trial Title:
A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Dosimetry of [177Lu]Lu-PSMA-617 in Chinese Adult Male Patients With Progressive PSMA-Positive mCRPC
NCT ID:
NCT05670106
Condition:
Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Conditions: Official terms:
Prostatic Neoplasms
Gallium 68 PSMA-11
Conditions: Keywords:
Chinese adult male population
therapeutic agent lutetium (177Lu) vipivotide tetraxetan
[177Lu]Lu-PSMA-617
radiolabeled compound gallium (68Ga) gozetotide
[68Ga]Ga-PSMA-11
Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer
Overall Response Rate
ORR
Prostate-specific Membrane Antigen
PSMA
Taxane
Androgen Receptor Pathway Inhibitor
ARPI
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
[177Lu]Lu-PSMA-617
Description:
Administered intravenously once every 6 weeks (1 cycle) for a maximum of 6 cycles.
Arm group label:
[177Lu]Lu-PSMA-617 plus best supportive/best standard of care (BS/BSOC)
Intervention type:
Other
Intervention name:
Best supportive/best standard of care (BS/BSOC)
Description:
Best supportive/best standard of care as defined by the local investigator
Arm group label:
[177Lu]Lu-PSMA-617 plus best supportive/best standard of care (BS/BSOC)
Intervention type:
Drug
Intervention name:
68Ga-PSMA-11
Description:
single intravenous dose of approximately 150 MBq. Administered dose must not be lower
than 111 MBq or higher than 259 MBq (3 - 7 mCi).
Arm group label:
[177Lu]Lu-PSMA-617 plus best supportive/best standard of care (BS/BSOC)
Summary:
The purpose of this study is to assess the efficacy, safety, tolerability,
Pharmacokinetic(s) (PK) and dosimetry of [177Lu]Lu-PSMA-617 when administered in addition
to Best Supportive/Best Standard of Care (BSC/BSoC) in Chinese participants with
progressive PSMA-positive mCRPC who received at least 1 novel androgen receptor pathway
inhibitor (ARPI) and were previously treated with 1 to 2 taxane regimens. Furthermore,
the safety, PK, and dosimetry of [68Ga]Ga-PSMA-11 are assessed.
Data from this study will be used to bridge global pivotal phase III study (VISION,
AAA617A12301) and to support China registration of [177Lu]Lu-PSMA-617 as a novel
anticancer modality, namely radioligand therapy, in mCRPC.
Detailed description:
This is a 2-part study:
1. Main part: Approximately 30 participants with at least 1 measurable lesion by
PCWG3-modified RECIST v1.1 criteria will be enrolled in the main part. The primary
endpoint of confirmed ORR will be analyzed with participants in this part, and will
be assessed via independent centralized review of radiographic images provided by
the Investigator and as outlined in PCWG3-modified RECIST v1.1 criteria.
2. Extension part: The extension part will enroll additional 30 participants with or
without measurable lesions following the main part. The secondary endpoints will be
analyzed with all participants in both main part and extension part.
Screening and enrollment period:
Written informed consent form (ICF) must be obtained prior to any screening procedures.
All screening procedures described in the Assessment Schedule must be completed within 28
days prior to enrollment, except for radiographic imaging assessment, which must be done
within 21 days prior to enrollment.
The participants will be assessed for eligibility and will undergo a mandatory
[68Ga]Ga-PSMA-11 Positron Emission Tomography (PET)/Computed Tomography (CT) scan to
evaluate Prostate-specific Membrane Antigen (PSMA) positivity for eligibility as assessed
by central readers. Only participants with PSMA positive cancer and confirmed eligibility
criteria will be enrolled.
Following completion of all required screening procedures and verifying participant
eligibility, the participant will be enrolled. [177Lu]Lu-PSMA-617 will be ordered in
parallel with interactive response technology (IRT) enrollment registration to allow at
least 2 weeks to order and deliver [177Lu]Lu-PSMA-617.
Treatment period:
In principle, all participants should begin [177Lu]Lu-PSMA-617 dosing within 14 days
after enrollment registration. However, Cycle 1 Day 1 (C1D1) can be delayed by up to an
additional 3 days only for unexpected scheduling delays. Participants will receive 7.4
Gigabecquerel (GBq) (200 Millicuries (mCi)) +/- 10% [177Lu]Lu-PSMA-617 once every 6 weeks
for a planned 6 cycles. BSC/BSoC may be used, including available care for the eligible
participants according to best institutional practice. ARPIs (e.,g., abiraterone, etc.)
are allowed. BSC/BSoC for each participant will be selected at the discretion of the
Investigator prior to [177Lu]Lu-PSMA-617 administration, and can be modified over time as
needed. BSC/BSoC will be administered per the physician's orders according to clinical
best practice.
Radiographic imaging (CT with contrast/Magnetic Resonance Imaging (MRI) and bone scan)
will be done at every 8 weeks (± 4 days) after first dose of [177Lu]Lu-PSMA-617 for the
first 24 weeks (independent of dose delays), then every 12 weeks (± 4 days) thereafter
and at End of Treatment (EOT) Visit (if not done within 28 days of EOT) until
radiographic disease progression confirmed by central reader, death, withdrawal of
consent, loss to follow-up, or subject/guardian's decision.
After the last day of study treatment period of [177Lu]Lu-PSMA-617 (i.e. after completion
of 6 cycles of treatment OR treatment discontinuation for any reason) [e.g. upon
radiographic progression as confirmed by blinded independent centralized review]), the
participants must have an EOT visit performed ≤ 7 days and enter into the Post-treatment
Follow-up period.
If a participant withdraws consent for the treatment period of the study, an EOT must be
done and the participant will enter into the Post-treatment Follow-up unless he
specifically withdraws consent for post-treatment Follow-up.
Post-treatment Follow-up period:
1. 30-day Safety Follow-up. All treated participants should have a safety follow-up
conducted approximately 30 days after EOT visit.
2. Long term Follow-up. The long-term follow-up starts after the 30-day Safety
follow-up and lasts until study completion. If a participant in the long term
follow-up period discontinues treatment for reasons other than BICR-determined
radiographic progression, his tumor assessments must be performed every 8 weeks
after first dose of study treatment for the first 24 weeks (week 9, 17, 25) and then
every 12 weeks (week 37, 49, etc) until confirmation of radiographic progression by
BICR. The long-term follow-up period will also include the collection of survival
and treatment updates, patient reported outcomes (PROs), serious adverse events
(suspected to be related to study treatment), as well as blood sampling for
hematology, chemistry testing, coagulation, and PSA. The visits will be carried out
every 12 weeks (± 4 weeks) until death, lost to follow-up, withdrawal of consent,
opposition to use data/biological samples or study completion, whichever occurs
first. This follow-up will allow the data collection on medically significant
long-term toxicities, such as long-term radiotoxicity.
If the participant withdraws consent for the collection of blood samples, PROs, and
imaging assessments during the long-term follow-up, the information on survival, serious
adverse events (SAEs) related to study treatment and post-treatment antineoplastic
therapy will be collected.
PK/dosimetry assessments:
Both PK and dosimetry of [68Ga]Ga-PSMA-11 will be evaluated in at least 10 and up to 12
participants (at least 6 participants in main part). PK and dosimetry of [68Ga]Ga-PSMA-11
can be evaluated in any participant regardless of his PSMA status.
Both PK and dosimetry of [177Lu]Lu-PSMA-617 will be evaluated in at least 10 and up to 12
participants (at least 6 participants in main part).
Participants who take part in PK and dosimetry evaluation of [177Lu]Lu-PSMA-617 will also
take part in the efficacy and safety evaluation together with the other participants. The
treatment and assessment procedure follow the same as above.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Written informed consent must be obtained before any assessment is performed.
2. Participants must be Chinese male adults >= 18 years of age.
3. Participants must have histological, pathological, and/or cytological confirmation
of prostate cancer.
4. Participants must be [68Ga]Ga-PSMA-11 PET/CT scan positive, and eligible as
determined by the sponsor's central reader according to the VISION read rules.
5. Participants must have a castrate level of serum/plasma testosterone (< 50 ng/dl, or
< 1.7 nmol/L).
6. Participants must have received at least one ARPI (such as enzalutamide
and/orabiraterone).
7. Participants must have been previously treated with at least 1, but no more than 2
previous taxane regimens.
- A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. If a
participant has received only 1 taxane regimen, the participant is eligible if:
the participants' physician deems him unsuitable to receive a second taxane
regimen (e.g., frailty assessed by geriatric or health status evaluation or
intolerance, etc.)
8. Documented progressive mCRPC, based on at least 1 of the following criteria:
- Serum/plasma PSA progression defined as 2 consecutive increases in PSA measured
at least 1 week apart, the minimal start value is 2.0 ng/ml
- Soft-tissue progression defined based on PCWG3-modified RECIST v1.1 (Eisenhauer
et al 2009, Scher et al 2016)
- Progression of bone disease: two new lesions; only positivity on the bone scan
defines metastatic disease to bone (PCWG3 criteria (Scher et al 2016)
9. Participants must have >= 1 metastatic lesion that is present on baseline CT, MRI or
bone scan imaging obtained =< 21 days prior to enrollment via central reading.
- In main part: participant must have at least one measurable lesion by
PCWG3-modified RECIST v1.1 via central reading
10. Participants must have adequate organ function:
- Bone marrow reserve:
- White blood cell (WBC) count >= 2.5 × 109/L OR absolute neutrophil count (ANC)
>= 1.5 × 109/L
- Platelets >=100 × 109/L
- Hemoglobin >= 9 g/dL
- Hepatic:
- Total bilirubin =< 1.5 x the institutional upper limit of normal (ULN). For
participants with known Gilbert's Syndrome =< 3 × ULN is permitted
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 3.0 × ULN
OR =< 5.0 × ULN for participants with liver metastases
- Renal:
- eGFR >= 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD)
equation
11. Albumin >3.0 g/dL.
Exclusion Criteria:
1. Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188,
Radium-223 or hemi-body irradiation.
2. Previous PSMA-targeted radioligand therapy.
3. Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological
therapy [including monoclonal antibodies], APRI is not included) within 28 days
prior to day of enrollment.
4. Any investigational agents (e.g. poly adenosine diphosphate-ribosyl polymerase
inhibitors [PARPi]) within 28 days prior to day of enrollment.
5. History of hypersensitivity to any of the study drugs or its excipients or to drugs
of similar chemical classes.
6. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or
investigational therapy.
7. Transfusion for the sole purpose of making a subject eligible for study inclusion.
8. Participants with a history of central nervous system (CNS) metastases who are
neurologically unstable, symptomatic, or receiving corticosteroids for the purpose
of maintaining neurologic integrity.
- Participants with CNS metastases are eligible if received therapy (surgery,
radiotherapy, gamma knife), asymptomatic and neurologically stable without
corticosteroids.
- Participants with epidural disease, canal disease and prior cord involvement
are eligible if those areas have been treated, are stable, and not
neurologically impaired.
9. Symptomatic spinal cord compression, or clinical or radiologic findings indicative
of impending cord compression.
Gender:
Male
Gender based:
Yes
Gender description:
Prostate cancer
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Novartis Investigative Site
Address:
City:
Guang Zhou
Zip:
510120
Country:
China
Facility:
Name:
Novartis Investigative Site
Address:
City:
Zhengzhou City
Zip:
450000
Country:
China
Facility:
Name:
Novartis Investigative Site
Address:
City:
Zhengzhou
Zip:
450008
Country:
China
Facility:
Name:
Novartis Investigative Site
Address:
City:
Wuhan
Zip:
430022
Country:
China
Facility:
Name:
Novartis Investigative Site
Address:
City:
Nanjing
Zip:
210006
Country:
China
Facility:
Name:
Novartis Investigative Site
Address:
City:
Shanghai
Zip:
200032
Country:
China
Facility:
Name:
Novartis Investigative Site
Address:
City:
Xian
Zip:
710032
Country:
China
Facility:
Name:
Novartis Investigative Site
Address:
City:
Xian
Zip:
710061
Country:
China
Facility:
Name:
Novartis Investigative Site
Address:
City:
Chengdu
Zip:
610041
Country:
China
Facility:
Name:
Novartis Investigative Site
Address:
City:
Beijing
Zip:
100034
Country:
China
Facility:
Name:
Novartis Investigative Site
Address:
City:
Beijing
Zip:
100036
Country:
China
Facility:
Name:
Novartis Investigative Site
Address:
City:
Beijing
Zip:
100730
Country:
China
Facility:
Name:
Novartis Investigative Site
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Facility:
Name:
Novartis Investigative Site
Address:
City:
Nanjing
Zip:
210036
Country:
China
Facility:
Name:
Novartis Investigative Site
Address:
City:
Shanghai
Zip:
200025
Country:
China
Facility:
Name:
Novartis Investigative Site
Address:
City:
Shanghai
Zip:
200032
Country:
China
Facility:
Name:
Novartis Investigative Site
Address:
City:
Shanghai
Zip:
200080
Country:
China
Facility:
Name:
Novartis Investigative Site
Address:
City:
Tianjin
Zip:
300308
Country:
China
Start date:
May 16, 2023
Completion date:
October 20, 2026
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/NCT05670106
