Safety of RAD301 in Healthy Human Volunteers and Patients With Pancreatic Cancer

Healthy Volunteers Clinical Trial

Official title: Characterizing the Radiochemical and Radiation Safety of RAD301 in Healthy Human Volunteers and Patients With Pancreatic Ductal Adenocarcinoma

Status Recruiting

Clinical Trial Summary

The objective of this clinical trial is to determine the safety of an intravenously administered radioisotope, RAD301 ([68Ga]-Trivehexin), in either health volunteers or patients with pancreatic cancer.

All subjects will undergo:

Screening, which entails physical examination and blood samples for standard blood testing.

Subjects that successfully pass screening will undergo:

Gallium-68 PET scanning procedures, which will occur during a single day (about 5-6 hours).

These subjects will return to the clinic at 2 weeks for additional safety labs. All scanned subjects will also be evaluated by telephone follow up on a weekly basis for 1 month after scanning.

Clinical Trial Description

Intervention Description: Single administrations of a radiopharmaceutical at a dose below the no observable (pharmacological) effect level (NOEL).

Primary Objective: To characterize the radiation and radiochemical safety profile of RAD301 in healthy adults and patients with PDAC.

Primary Endpoints:

1. Radiation Absorbed Doses in internal organs, in units of mGy and mSv;

2. Changes in VSs and ECGs, such as the PR and QTcF intervals; as percentages and absolute values approaching critical safety zones;

3. Changes in clinical laboratory tests of internal organ function; as percentages and absolute values outside the reference ranges of normal.

This study will enroll healthy volunteers (N=3) and patients with pancreatic ductal adenocarcinoma (PDAC; N=6) age 18 and older (no upper limit). Patients may be at any stage of their illness.

This will be a Phase 1a, open label, single dose, extended study of safety and biokinetics of RAD301 in three healthy human volunteers (HV) and six patients with pancreatic ductal adenocarcinoma (PDAC). The procedures will be nearly identical in both groups, but there could be more scans in HVs during the day and fewer in patients during the same time interval simply because patients might not have the tolerance for lying still on an imaging table for very long. In all participants, vital signs (VSs) will be measured, electrocardiograms (ECGs) will be acquired, and blood will be sent to the clinical laboratory for safety assessments before-and-after a single dose, intravenous (IV) administration of the investigational radiopharmaceutical, RAD301. Vital signs (VSs) will be re-measured, electrocardiograms (ECGs) will be acquired again, and additional blood will be sent to the clinical laboratory for repeat safety assessments at multiple times post-injection (p.i.). There will be two (2) whole body (WB) PET-CT scanning sessions. The initial PET scanning session starts at the time of injection by acquiring dynamic images of the heart and aorta to quantify the imaging-derived input function (IDIF). After approximately 6-to-10 minutes, scanning will shift to acquiring WB images of up to 200 cm from head-to-toe, with 150 cm much more typical because the knees will be bolstered, and the neck will be flexed. The initial WB acquisition should take approximately ten (10) minutes. As time passes and less and less radioactivity is localizable to the distal extremities, the scan length may be decreased from vertex-to-thighs. The duration of each scan may increase to partially compensate for radioactive decay. More than one WB scan may be performed in volunteers during the first imaging session, but only one scan will be required in patients with PDAC who are not feeling well. The subjects will then be given a rest period ("lunch break") after which the sequence of events could be repeated. This second imaging session will be optional, and depend on the robustness of the subject AND the availability of the clinical scanner. There will be one last, or "final" imaging session at the end of the day for all subjects, which will strive to include the time interval after about four (4) physical half-lives of Gallium-68. The primary outcome measure will be related to radiation safety. Estimates of radiation absorbed doses will be derived from the areas under the time-activity curves (AUCs) for internal organs. Co-primary clinical safety measures will include changes in vital signs, ECG parameters (such as the PR and corrected QT intervals) and clinical laboratory tests (such as white blood cell counts that are indicative of immune system activation and proteins that reflect excretory function). Secondary endpoints will include the time-activity curves (TACs) and total volumes of distribution (VT) of radiopharmaceutical in the internal organs.

Subjects will be in the study for up to eight (8) weeks from the time they first meet with the study team until the last telephone call. Screening may occur anytime for up to five (5) weeks before the first PET imaging procedure. The two imaging sessions will take approximately one day. One physical visit at the site for clinical safety lab and surveillance of adverse events two (2) weeks after administration of RAD301 will take about 20 minutes. Follow up surveillance for adverse events takes about 10 minutes per phone at day 2, week 1, and 4.

The time a subject will need to set aside during each period will be as follows:

• A pre-study telephone screening should take less than 15 minutes.

• Period 1: screening. Two (2) hours or less.

• Period 2: RAD301 ([68Ga]-Trivehexin) administration and serial safety studies with PET imaging sessions. One day.

• Period 3: one month for post study surveillance of adverse events (AEs) with one physical visit at the site for standard blood lab safety testing 2 weeks after administration of RAD301 and phone calls of about 5-to-20 minutes or less on Day 2, Day 8, and Day 29, all +/- 2 days, after the PET scanning session.

The first in-person screening session will take about two hours. The sessions encompassing serial PET scans will take approximately one day, nominally corresponding to five (5) physical half-lives of [68Ga]. Follow up phone calls for AE surveillance should take less than 15 minutes or less each. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Healthy Volunteers
• Pancreatic Ductal Adenocarcinoma

• NCT number: NCT05799274
• Study type: Interventional
• Source: Radiopharm Theranostics, Ltd
• Contact: Lionel S Zuckier, MD
• Phone: (+1) 718 405 8454
• Email: LZuckier@montefiore.org
• Status: Recruiting
• Phase: Phase 1
• Start date: November 9, 2023
• Completion date: September 2024