Targeted Radionuclide Therapy in Metastatic Prostate Cancer Using a New PSMA Ligand Radiolabelled With Terbium-161 (161Tb-SibuDAB) - Dose Identification/Escalation Phase Ia/b Study

NCT06343038 | Recruiting Phase 1 DMC

• 1 other identifier: 2023-01868; th23Nicolas
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Researchers will test a new treatment for prostate cancer. This treatment uses an antibody tagged with a small amount of radioactive material. Researchers believe the new antibody might work better than those used before. In the first part of the study researchers will compare the new treatment to the old one on prostate cancer patients using very low doses, not strong enough to treat nor to cause strong adverse reactions. Each patient will eventually receive both treatments, but one at a time. The aim of the second part of the study is to find the best dose of the new treatment for patients. This means finding the dose that offers the most benefits with the fewest side effects. The performance of different prostate cancer diagnostic methods is also in scope of the study.

Conditions

Castration-resistant Prostate Cancer

Keywords

Radioligand Therapy; Phase Ia/Ib; Circulating Tumour Cells; Biomarkers Development; Voxel-based 3D Dosimetry

Outcome Measures

Primary Outcomes (2)

• Phase Ia: Tumour absorbed dose

  Comparison of median tumour absorbed dose, in Gy, after sequential injections of non-therapeutic test activity of 161Tb-SibuDAB and 177Lu-PSMA I\&T in the same patients. Tumour absorbed dose is obtained by SPECT/CT of head, thorax, abdomen and pelvis and represents the time integrated tumour activity (3 tumours per patient). To avoid carry-over effects, a period of at least 21 days will be allowed between the two consecutive test injections.

  3, 24, 48 and 168 hours after each injection

• Phase Ib: Identification of the optimal biological dose of 161Tb-SibuDAB for mCRPC RLT

  Identification of the optimal biological dose of 161Tb-SibuDAB, in GBq, for mCRPC RLT. The optimal maximum tolerated dose / biological dose will be the highest 161Tb-SibuDAB injected activity which elicits a clinically relevant adverse event grade G3 (according to CTCAE 5.0, ranging from G1 to G5 where G1 corresponds to mild AE and and G5 corresponds to AE related death) in maximal 1 patient per cohort / 1 patient in two cohorts.

  baseline and 1 week, 2 weeks and 4 weeks after each injection. Long term: 6 and 12 months after RLT

Secondary Outcomes (4)

• Phase Ia: Estimation of critical organ median absorbed doses

  3, 24, 48 and 168 hours after each injection

• Phase Ia: Estimation of the median tumour-to-critical organ absorbed dose ratios

  3, 24, 48 and 168 hours after each injection

• Phase Ib: Cumulative median tumour and organ absorbed doses after 4 cycles of 161Tb-SibuDAB RLT

  3, 24, 48 and 168 hours after each injection

• Phase Ib: Estimation of the "therapy index" for 161Tb-SibuDAB RLT.

  3, 24, 48 and 168 hours after each injection

Study Arms (3)

Cross-Over Group A

ACTIVE COMPARATOR

Cross-over design (n=10, random allocation at a 1:1 ratio). Event order: 1. Injection of 1 GBq of 161Tb-SibuDAB, 2. 3 weeks washout period, 3. Injection of 1GBq of 177Lu-PSMA-I\&T

Drug: Injection, 161Tb-SibuDAB,1GBq; Drug: Injection, 177Lu-PSMA-I&T, 1GBq

Cross-Over Group B

ACTIVE COMPARATOR

Cross-over design (n=10, random allocation at a 1:1 ratio). Event order: 1. Injection of 1 GBq of 177Lu-PSMA-I\&T, 2. 3 weeks washout period, 3. Injection of 1GBq of 161Tb-SibuDAB

Drug: Injection, 161Tb-SibuDAB,1GBq; Drug: Injection, 177Lu-PSMA-I&T, 1GBq

Dose Escalation Study

EXPERIMENTAL

Arm composed of 5 patient cohorts each with 3-patients. Treatment consists of 4 cycles of 161Tb-SibuDAB based on the available MTD and DLT findings. Safety and efficacy evaluation performed after each therapy cycle.

Drug: Injection, 161Tb-SibuDAB, Dose Escalation

Interventions

Injection, 161Tb-SibuDAB,1GBq DRUG

Intravenous injection via peripheral venous catheter of \~1GBq 161Tb-SibuDAB (\~200 μg / \~125 nM) in saline

Cross-Over Group A; Cross-Over Group B

Injection, 177Lu-PSMA-I&T, 1GBq DRUG

Intravenous injection via peripheral venous catheter of \~1GBq 161Tb-SibuDAB (\~100 μg / \~65 nM) in saline

Cross-Over Group A; Cross-Over Group B

Injection, 161Tb-SibuDAB, Dose Escalation DRUG

Intravenous injection via peripheral venous catheter of 161Tb-SibuDAB in saline. The intervention comprises 4 cycles at 6-week intervals. The 161Tb-SibuDAB entry activity will be calculated based on dosimetry and toxicity data from the first 3 patients in Phase Ia of the study. The escalated or de-escalated 161Tb-SibuDAB activity for the subsequent 3-patient cohorts will be determined based on the clinical and biochemical safety information and on organ dosimetry results of the entry/previous cohort. Up to 4 escalation or de-escalation steps will be performed.

Dose Escalation Study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Consent form signed
• Male patients with age \> 18 years
• Clinical indication for RLT with 177Lu-PSMA-I\&T (progressive PSMA-positive mCRPC patients after androgen receptor signalling pathway inhibitor and taxan-based chemotherapy or patient unfit for chemotherapy)
• Patients will be included in Phase Ia while being under active therapy with 177Lu-PSMA-I\&T (SoC) and after they have completed the first two cycles of 177Lu-PSMA-I\&T RLT
• At least 3 measurable tumours on PSMA PET/CT (\>1.5 cm) with sufficiently intense PSMA uptake (SUVmax\>20)
• ECOG Performance status: 0-1
• Blood parameters: a) Leucocytes ≥ 3 G/L; b) Haemoglobin ≥ 100 g/L; c) Thrombocytes ≥ 100 G/L
• Estimated glomerular filtration rate (eGFR) \> 45 ml/min
• Albumin \> 25 g/L
• ALT, AST, AP: ≤ 5 times upper standard value
• Bilirubin ≤ 2 times upper standard value
• For male patients who are not surgically sterilized (orchiectomy or vasectomy), appropriate contraceptive measures must be taken during RLT and until 4 months after completion of RLT. As acceptable contraceptive count sexual abstinence or double contraceptive methods: hormonal contraceptive (oral, transdermal, implants or injections) in combination with barrier methods (spiral, condom, diaphragm)

You may not qualify if:

• Prior PSMA-targeted RLT (except for the 2 first cycles in Part Ia)
• PSMA-negative (or PSMA-negative / FDG-positive) disease
• Known intolerance against DOTA, DOTAGA, urea-based analogues or against any of the components/formulation of 177Lu-PSMA-I\&T or 161Tb-SibuDAB solutions.
• Ongoing infection at the screening visit or a serious infection in the past 4 weeks
• Administration of another investigational product in the last 60 days before Visit 1 Day 1
• Prior or planed administration of a therapeutic radiopharmaceutical during 8 half-lives of the used radio-pharmaceutical's radionuclide, also during the ongoing study
• Any uncontrolled significant medical, psychiatric or surgical condition (active infection, unstable angina pectoris, cardiac arrhythmia, poorly controlled hypertension, poorly controlled diabetes mellitus \[HbA1c ≥ 9%\], uncontrolled congestive heart disease, etc.) or laboratory findings that might jeopardize the patient's safety or that would limit compliance with the objectives and assessments of the study. Any mental conditions which prevent the patient from understanding the type, extent and possible consequences of the study and/or an uncooperative attitude from the patient.
• Current history of any malignancy other than prostate cancer within 5 years of enrolment except for fully resected non-melanoma skin cancer

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel

Basel, 4031, Switzerland

RECRUITING

MeSH Terms

Interventions

Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Alin Chirindel, MD

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Damian Wild, MD

CONTACT

+41 61 328 66 83; damian.wild@usb.ch

Alin Chirindel, MD

CONTACT

+41 61 328 63 75; alin.chirindel@usb.ch

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In Phase Ia: Radiation dosimetry driven, head-to-head in cross-over design comparison of tumour and critical organ absorbed doses after sequential non-therapeutic injections of 161Tb-SibuDAB and 177Lu-PSMA-I\&T in the same mCRPC patients undergoing standard 177Lu-PSMA-I\&T RLT. In Phase Ib: Clinical and radiation dosimetry-based dose escalation study, with a classical 3+3 design, to identify the optimal biologic dose (injected activity) of 161Tb-SibuDAB for safe and effective RLT.

Study Record Dates

• First Submitted: March 26, 2024
• First Posted: April 2, 2024
• Study Start: February 20, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: August 14, 2024

Record last verified: 2024-08

Locations

CH (1)