This study has been transitioned to CTIS with ID 2023-509881-39-00 check the CTIS register for the current data. The aim of this study is to evaluate the difference in the fraction of patients that have disease progression within 6 months after…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
- Prostatic disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main goal of this study is to assess the difference in the fraction of
patients that have disease progression during the 6 month follow up of this
study after 177Lu-PSMA RLT or a deferred androgen deprivation treatment
schedule.
Secondary outcome
Secondary endpoints will be the ADT free survival, PSA response, toxicity
defined by NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0),
radiological state of the disease expressed in the difference in amount and
size of suspicious nodes 18F-PSMA PET/CT and (whole body) MRI between pre- and
post-therapy and quality of life assessments.
Background summary
Radioligand therapy (RLT) is a promising new therapeutic approach to treat
metastatic prostate cancer. This tumor-specific treatment is directed against
prostate-specific membrane antigen (PSMA), which is overexpressed in prostate
cancer cells. In the last few years, several lutetium-177 (177Lu, β emitter)
labeled PSMA ligands have been developed and are currently applied in nuclear
medicine departments worldwide to treat metastatic castrate resistant prostate
cancer (mCRPC) patients. A large retrospective study reported an overall
biochemical response rate of 45% following multiple 177Lu-PSMA RLT cycles in
mCRPC patients, while 40% of patients already responded after a single cycle.
RLT with 177Lu-PSMA was generally well tolerated and 12% of the patients
suffered grade 3 to 4 hematological toxicity. In addition, mild and often
transient xerostomia occurred in 8%.(1) A prospective study carried out in
Australia confirmed these results recently.(2) Based on these promising
outcomes Endocyte (a Novartis company) is currently carrying out an
international multicenter prospective registration study for end-stage mRCPC
patients (ClinicalTrials.gov Identifier: NCT03511664).
Although these results are promising, it is noteworthy that most of the
currently available data is retrospective and 177Lu-PSMA RLT has only been
evaluated in end stage prostate cancer patients to date. Based on the mode of
action, RLT could be more effective in low volume disease because of the very
high tumor uptake of radioligands in small lesions. In Radboudumc we initiated
a pilot study to evaluate the doses delivered to the tumors and organs at risk
as well as the toxicity of 177Lu-PSMA RLT in an earlier disease stage; low
volume metastatic hormone sensitive prostate cancer patients. All patients were
currently treated under this protocol of which 4 completed the study entirely,
including the six month follow up. None of the patients had any high grade
treatment related toxicity. All did show a good response to the treatment with
one patient having a complete remission on imaging. Notably, all four patients
had a PSA doubling time of less than six months before inclusion and all of
them postponed other treatments (e.g. androgen deprivation therapy; ADT) for
six months and three out of the four patients postponed hormonal treatment for
over 10 months. In summary, we were able to show, that 177Lu-PSMA treatment is
safe coupled with promising response rates and postponing hormonal treatment by
conserving good quality of life.
Here we propose a multicenter randomized clinical trial to investigate the
efficacy of 177Lu-PSMA RLT in patients with low volume metastatic prostate
cancer, prior to the hormone insensitive state.
Study objective
This study has been transitioned to CTIS with ID 2023-509881-39-00 check the CTIS register for the current data.
The aim of this study is to evaluate the difference in the fraction of patients
that have disease progression within 6 months after applying 177Lu-PSMA RLT in
patients with low volume, hormone sensitive metastatic prostate cancer.
Ultimately, the goal is to stabilize previously progressive disease in this
patient cohort and to improve the quality of life by postponing the need for
ADT.
Study design
This is a multi-center, two-arm randomized phase II study. Patients randomized
to the control arm are eligible to receive 177Lu-PSMA RLT if they meet the end
of treatment (EOT) 1 criteria and are willing to undergo a 177Lu-PSMA RLT. This
cohort will be analyzed separately for secondary study objectives.
Intervention
A maximum of 2 (expandable to 4 if clinically benefiting) cycles of 177Lu-PSMA
radioligand therapy (RLT).
Study burden and risks
The study will require time and effort from participating patients. They will
undergo a 18F -PSMA PET/CT and a (whole body) MRI scan prior to inclusion and 6
months after the last treatment. Also, for monitoring, they will receive
several blood draws for safety and response evaluation. The extensive
monitoring is also beneficial for patients.
A potential risk is the therapeutic injection with 177Lu-PSMA RLT itself, as it
is not completely clear yet what the long term toxicity of this new treatment
is. However, it is important to note that the administered radiation doses are
in the lower range of the previously published data in mCRPC patients. And
importantly, treatment with 177Lu-PSMA RLT shows potential in stabilization of
previously progressive malignant disease and may maintain/improve the quality
of life of patients with low volume prostate cancer by postponing the need for
ADT (and thus postponing hormonal treatment related toxicity).
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
- Histological proven adenocarcinoma of the prostate with archived tumor
material.
- Biochemical recurrence or clinical progression (PSA > 1.0 µg/l).
- ECOG 0-1.
- PSA-doubling time < 6 months.
- 18F-PSMA-PET-CT positive metastases in bones and/or lymph nodes (N1/M1ab):
>=1, maximally 5 metastases.
- Local treatment for oligometastases with radiotherapy or surgery appears to
be no option anymore (due to prior treatment or the location of the metastatic
lesions).
- No prior hormonal therapy (including any androgen directed treatment such as
Bicalutamide, Apalutamide, Abiraterone or Enzalutamide) or taxane based
chemotherapy (docetaxel or cabazitaxel); testosterone > 1.7 nmol/l.
Exception: local prostate cancer treated with local radiotherapy plus adjuvant
ADT; these patients need to be stopped with ADT at least 6 months.
- No visceral metastases.
- Laboratory values:
• White blood cells > 3.0 x 10^9/l
• Platelet count > 75 x 10^9/l
• Hemoglobin > 6.2 mmol/l
• ASAT, ALAT < 3 x ULN
• MDRD-GFR >= 50 ml/min
- Signed informed consent.
Exclusion criteria
- A detectable lesion on the 18F-PSMA PET/CT with significant PSMA avidity,
defined by a SUVmax > 10 (partial volume corrected).
- A known subtype other than prostate adenocarcinoma.
- Previous PSMA based radioligand treatment.
- Visceral or brain metastases.
- Any medical condition present that in the opinion of the investigator will
affect patients* clinical status when participating in this trial.
- Prior hip replacement surgery potentially influencing performance of PSMA
PET/CT.
- Sjogren's syndrome.
- A second active malignancy other than prostate cancer.
- Patients who are sexually active and not willing/able to use medically
acceptable forms of barrier contraception.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-509881-39-00 |
| EudraCT | EUCTR2020-000076-37-NL |
| CCMO | NL72585.091.20 |