This study has been transitioned to CTIS with ID 2024-514168-15-00 check the CTIS register for the current data. Primary: To determine the maximum tolerated dose (MTD) of 1 or 2 cycli Lu-PSMA when given concurrent with EBRT+ADT. Secondary: To…
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
- Prostatic disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint: The maximum tolerated dose (MTD) of the 4 selected doses of
Lu-PSMA (3, 6, 9 or 2x7.4 GBq) when administered in combination with EBRT.
Dose-limiting toxicity (DLT) will be acute toxicity CTCAE v 5.0 grade 3 of any
type occurring from start of EBRT until 3 months after, determined to be
related to study treatment.
Secondary outcome
Secondary outcomes: late toxicity according to CTCAE v 5.0 at 6 months, PSA
response at 6 months, quality of life according to EORTC QLQ-C30 and -PR25
questionnaires, combined dosimetry based on added dose distributions from
EBRT+Lu-PSMA, and in vivo pharmacokinetics of Lu-PMSA during EBRT based on
biodistribution imaging and blood samples.
Background summary
In the past, prostate cancer patients with nodal metastases (clinically N1M0)
were not considered for curative treatment, based on the hypothesis that these
patients are affected by systemic disease. Today, patients with primary
diagnosed N1M0 prostate cancer increasingly receive curative intent high-dose
external beam radiotherapy (EBRT) to the prostate and regional nodes combined
with up to 3 years androgen deprivation therapy (ADT). This aggressive and
lengthy multimodal treatment can achieve long-term disease-free and overall
survival, but it also comes with significant toxicity and failure rates of up
to 47% within 5 years with locoregional recurrence within radiotherapy fields
and/or distant progression. A new strategy is needed to (1) enhance EBRT to
better control macroscopic tumor in the prostate and involved nodes, (2) better
treat undetected microscopic disease inside and outside EBRT fields, and (3)
potentially reduce or obviate the long use of ADT with its toxicity and
associated poor quality of life. Radioligand therapy (RLT) with Lutetium-177
labeled PSMA-ligands (Lu-PSMA) can selectively deliver radiation dose to both
macroscopic and microscopic tumor locations throughout the body, with limited
systemic toxicity. Based on radiobiologic considerations, the hypothesis is
that complementing EBRT with concurrent Lu-PSMA can provide synergistic
anti-tumor effects, without prolonging overall treatment time and with limited
toxicity. The feasibility of this innovative use of *RNT as the ultimate
radiosensitizer for EBRT* now needs to be explored.
Study objective
This study has been transitioned to CTIS with ID 2024-514168-15-00 check the CTIS register for the current data.
Primary: To determine the maximum tolerated dose (MTD) of 1 or 2 cycli Lu-PSMA
when given concurrent with EBRT+ADT. Secondary: To demonstrate acceptable late
toxicity at 6 months, superior dosimetric efficacy, anti-tumor efficacy at 6
months, feasibility of QoL evaluation, favorable pharmacokinetics.
Study design
Multicenter prospective phase I dose-escalation study, using a BOIN design,
with 4 dose levels for Lu-PSMA and a maximum of 24 patients.
Intervention
Standard of care treatment (EBRT of prostate and pelvic nodes with concurrent
ADT) is complemented with 1/2 concurrent cycle dose-escalated Lu-PSMA in week 2
(and 4).
Study burden and risks
Participation in the study involves one day hospitalization per administration
with IV catheter and administration of 3, 6, 9 or 2x7.4 GBq 177Lu-PSMA-617 in
week 2 (and week 4) of EBRT, and during the week after each administration 3
SPECT/CT scans from pelvis to head for dosimetry and 11 blood samples for
pharmacokinetics. Patient receive additional radiation exposure from Lu-PSMA,
which comes with a low risk for acute toxicity (infusion reaction, nausea,
vomiting), low risk for late toxicity (temporary salivary gland function loss),
a maximum of one or two days hospitalization in isolation, and after discharge
about 2 weeks radiation safety measures at home. These disadvantages are
considered acceptable for patients with node-positive prostate cancer, in the
scope of potential improvements in tumor control with associated benefits in
survival and QoL, for included patients as well as for future patients.
Plesmanlaan 121
AMSTERDAM 1066CX
NL
Plesmanlaan 121
AMSTERDAM 1066CX
NL
Listed location countries
Age
Inclusion criteria
- Histologically proven prostate cancer;
- cT2-4, partly determined by MRI;
- N1, determined by LND/SNP and/or PSMA PET/CT;
- iM0, determined by PSMA PET/CT;
- Accepted for curative intent treatment with EBRT of the prostate and regional
nodes + 3y ADT;
- Visually PSMA-positive primary tumor and nodes, largest lesion higher or
equal to average liver uptake;
- WHO performance score 0-1;
- Age > 18 years;
- For patients who have partners of childbearing potential: Willingness to use
a method of birth control with adequate barrier protection as described in
section 4.4 during the study and for 6 months after the study drug
administration; and
- Signed written informed consent.
Exclusion criteria
- Inability to comply to study procedures;
- Inability to adhere to radiation safety measures in hospital or at home;
- Inability to undergo the required biodistribution scans;
- Prior or current malignant disease with potential impact on treatment outcome
or survival;
- Prior treatment with EBRT;
- Prior treatment with ADT, already initiated >1 month before the start of EBRT;
- Prior treatment with radionuclide therapies, Lu-PSMA or other;
- Reduced bone marrow reserve (Hb<6 mmol/L, Leukocytes<2.5 10E9/L, or
Platelets<100 10E9/L not older than 1 month before start of EBRT);
- Reduced renal function (GFR < 60 not older than 1 month before start of EBRT);
- Reduced salivary gland function (history of prior salivary gland disease); or
- Miction problems requiring pre-treatment with ADT.
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 | CTIS2024-514168-15-00 |
| EudraCT | EUCTR2020-005577-27-NL |
| CCMO | NL75976.031.21 |