Molecular Imaging of DNA Damage Response by [18F]-Olaparib PET ([18F]-olaparib)

This is a single-centre, non-randomized, two-stage design, proof-of-concept study evaluating the radiolabelled PARP inhibitor [18F]-olaparib als potential tracer for imaging of tumour PARP expression by PET.

Study Overview

• Status: Not yet recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma (HNSCC)
• Intervention / Treatment: Diagnostic test: [18F]-olaparib PET scan

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Michel van Kruchten, MD, PhD; Phone Number: +31 50 361 2821; Email: m.van.kruchten@umcg.nl

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen
    • Contact: Michel van Kruchten, MD, PhD; Phone Number: +31 50 361 2821; Email: m.van.kruchten@umcg.nl
    • Contact: Michel van Kruchten, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients >18y, with biopsy-proven HPV-negative HNSCC, or patients >40y with HPV-positive HNSCC and high-risk features (i.e. > 10 smoke packs/year AND ≥N2b)
2. Treatment with chemoradiotherapy using platinum-based chemotherapy is anticipated
3. Recent archival tumour tissue (<8 weeks prior to inclusion) should be available with suffi-cient residual material for determination of tumour PARP1 levels
4. Presence of a tumour lesion ≥10 mm in diameter
5. ECOG performance status 0-2
6. Negative pregnancy test in women with childbearing potential
7. Life expectancy >3 months
8. Signed written informed consent and able to comply with the protocol
9. For stage II only: re-biopsy should be deemed feasible by the investigators (assessed by head-and-neck surgeon)

Exclusion Criteria:

1. Recent treatment with PARP inhibitors or other investigational therapies <30 days.
2. Presence of significant co-morbidities that make participation in the study undesirable according to the treating physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage I; Five patients with HNSCC will undergo a dynamic [18F]-olaparib PET during 30 min, followed by a static whole body PET scans at 120 min post-injection of [18F]-olaparib.	Diagnostic test: [18F]-olaparib PET scan; The IMP investigated is [18F]Olaparib, a radiolabelled PARP inhibitor suitable for PET imaging.
Experimental: Stage II; After determination of the most optimal time point for imaging, five patients with HNSCC scheduled for chemoradiotherapy will undergo serial [18F]-olaparib PET at baseline (i.e. prior to treatment initiation) and a second scan during the first week of chemoradiotherapy. Patients in stage II will undergo a study biopsy in the first week of chemoradiotherapy to evaluate changes in PARP protein expression.	Diagnostic test: [18F]-olaparib PET scan; The IMP investigated is [18F]Olaparib, a radiolabelled PARP inhibitor suitable for PET imaging.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dosimetry assessment	Assess dosimetry, most optimal time point for imaging (Stage I), and safety of [18F]olaparib PET (Stage I + II)	6-12 months
Correlation between tumour uptake and expression	Determine the correlation between tumour [18F]-olaparib uptake and tumour PARP-1 expression levels on tumour biopsy (Stage I + II).	12-18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of changes in tumour uptake	Evaluate changes in tumour [18F]-olaparib uptake, as a read-out of DNA damage, during treatment with platinum-based chemoradio-therapy, and its correlation with changes in PARP protein expression (Stage II).	12-18 months

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Principal Investigator: Michel van Kruchten, MD, PhD, University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: June 25, 2024
• First Submitted That Met QC Criteria: June 25, 2024
• First Posted (Actual): July 1, 2024

Study Record Updates

• Last Update Posted (Actual): April 18, 2025
• Last Update Submitted That Met QC Criteria: April 15, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Poly(ADP-ribose) Polymerase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Olaparib
• Other Study ID Numbers: 19310

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No