A Phase I, open-label, multi-center study of radiation dosimetry, safety, and tolerability of extended lutetium (177Lu) vipivotide tetraxetan treatment in chemo-naïve adults with metastatic castration-resistant prostate cancer: RADIOpharmaceutical DOSimetry Evaluation (RADIODOSE) study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Nov 2024 → ongoing

Decision date (initial)

2024-10-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novartis Pharma AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Dose response

-To assess organ dosimetry of AAA617 following the administration of 7.4 GBq (±10%) for up to 12 cycles in taxane-naïve participants with progressive PSMA-positive mCRPC with normal kidney function or mild renal impairment.
- To assess the safety of AAA617 following the administration of 7.4 GBq (±10%) for up to 12 cycles in taxane-naïve participants with progressive PSMA-positive mCRPC with normal kidney function or mild renal impairment.
-To assess the tolerability of AAA617 following the administration of 7.4 GBq (±10%) for up to 12 cycles in taxane-naïve participants with progressive PSMA-positive mCRPC with normal kidney function or mild renal impairment.

Secondary objectives 10

1. -To assess tumor dosimetry of AAA617 following the administration of 7.4 GBq (±10%) for up to 12 cycles in taxane-naïve participants with progressive PSMA-positive mCRPC with normal kidney function or mild renal impairment.
2. -To assess pharmacokinetics (PK) of AAA617.
3. -To assess the efficacy of AAA617 with respect to overall response rate (ORR) based on Prostate Cancer Working Group 3 (PCWG3) modified-RECIST 1.1 per local investigator assessment
4. -To assess the efficacy of AAA617 with respect to disease control rate (DCR) based on PCWG3 modified-RECIST 1.1 per local investigator assessment.
5. -To assess the efficacy of AAA617 with respect to duration of response (DOR) based on PCWG3 modified-RECIST 1.1 per local investigator assessment.
6. -To assess the efficacy of AAA617 with respect to radiographic progression-free survival (rPFS) based on PCWG3 per local investigator assessment.
7. -To assess the efficacy of AAA617 with respect to PSA response per PCWG3.
8. -To assess the safety of AAA617 following the administration of 7.4 GBq (±10%) for up to 12 cycles in taxane-naïve participants with progressive PSMA-positive mCRPC with normal kidney function or mild renal impairment in terms of overall survival.
9. -To assess additional safety parameters of AAA617 following the administration of 7.4 GBq (±10%) for up to 12 cycles in taxane-naïve participants with progressive PSMA-positive mCRPC with normal kidney function or mild renal impairment.
10. -To assess additional tolerability parameters of AAA617 following the administration of 7.4 GBq (±10%) for up to 12 cycles in taxane-naïve participants with progressive PSMA-positive mCRPC with normal kidney function or mild renal impairment.

Conditions and MedDRA coding

Metastatic Castration-Resistant Prostate Cancer

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002419-PIP02-18, EMEA-002577-PIP01-19

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. - Participants must be adults ≥ 18 years of age.
2. -Participants must have an ECOG performance status ≤ 1
3. -Participants must have histological confirmation of adenocarcinoma of the prostate.
4. -Participants must be PSMA-positive per gallium (68Ga) gozetotide (also referred to as [68Ga]Ga-PSMA-11 or radiolabeled AAA517 and 68 Ga-PSMA-11) positron emission tomographic–computed tomographic (PET/CT) scans at baseline with at least 1 lesion showing intermediate or high uptake level (PSMA expression score 2 or 3 per PROMISE V2 criteria and no lesions meeting the size criteria as defined in the read rules showing PSMA expression scores 0 or 1 as determined by the central reader.
5. -Participants must have a castrate level of serum/plasma testosterone (≤50 ng/dL or ≤1.7 nmol/L) either by pharmaceutical or surgical methods.
6. -Participants must have progressed only once on prior second generation ARPIs (abiraterone, enzalutamide, darolutamide, or apalutamide).

Exclusion criteria 4

1. -Previous treatment with any of the following within 6 months of study enrollment: Strontium‑89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation
2. -Any previous radioligand therapy.
3. -Prior treatment with cytotoxic chemotherapy for metastatic castration-resistant prostate cancer(mCRPC) (e.g., taxanes, platinum, estramustine, vincristine, methotrexate, etc.), immunotherapy or biological therapy [including monoclonal antibodies]. [Note: Taxane exposure (maximum 6 cycles) is allowed if 12 months have elapsed since completion of this therapy in pre-mCRPC setting. Prior treatment with sipuleucel-T is allowed].
4. -Any investigational agents within 42 days prior to the day of the first RLT treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. -Time activity curves (TACs) and absorbed radiation dose of AAA617 in organs.
2. -Incidence and severity of adverse events (AEs) and serious AEs (SAEs)
3. -AAA617 dose reductions, interruptions, discontinuations

Secondary endpoints 10

1. -TACs and absorbed radiation doses of AAA617 in tumors
2. -Concentrations of AAA617 in blood over time and derived PK parameters from blood radioactivity data.
3. -ORR is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR) per investigator assessment and according to PCWG3 modified-RECIST v1.1.
4. -DCR is defined as the proportion of CR, PR, stable disease or non-CR/non-PD per investigator assessment and according to PCWG3 modified-RECIST v1.1 assessment in soft tissue, lymph node, and visceral lesions.
5. -DOR is defined as the duration of time between the date of the first documented BOR (CR or PR) per investigator assessment according to PCWG3 modified-RECIST v1.1 and the date of first documented progression or death due to any cause.
6. -Radiographic progression free survival (rPFS) defined as the time from the date of first dose of study treatment to the date of the first documented radiographic disease progression as assessed by investigator and PCWG3 modified-RECIST v1.1 criteria or death due to any cause, whichever occurs first.
7. -Prostate specific antigen (PSA) response is defined as proportion of participants who achieve any decrease from baseline that is confirmed by a second PSA measurement ≥4 weeks. participants with any decrease in PSA will also be summarized by visit.
8. -Overall survival is defined as the time from the first dose of study treatment to death due to any cause.
9. -Changes in safety laboratory parameters, vital signs, electrocardiogram (ECG).
10. -Duration of exposure to AAA617 and dose intensity.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 17

Locations

3 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Application history

5 submissions — initial application plus substantial / non-substantial modifications