Abstract 3224
Background
High risk lymph node positive non-metastatic (N+M0) prostate cancer (PCa) patients (pts) are treated with pelvic radiotherapy (RT) and androgen deprivation therapy (ADT), which can lead to significant toxicity. Docetaxel (Doc) has been acknowledged for its radiosensitizing activity. Chemoradiation with RT on the primary tumour could improve local and systemic control, while avoiding toxicity of pelvic RT. This has been investigated in 6 trials with weekly intravenous Doc. Oral chemotherapy is often preferred, improves cost-effectiveness and avoids dexamethasone prophylaxis. However, oral Doc treatment is challenging due to a low systemic uptake. Co-administration of ritonavir (r), a Cyp3A4 and P-glycoprotein inhibitor, and formulation of water soluble tablets (ModraDoc006), increased the bioavailability of orally given Doc (ModraDoc006/r). This phase I study assesses the pharmacokinetics (PK), safety and maximum tolerated dose (MTD) of ModraDoc006/r, given with IMRT and ADT in high risk N+M0 PCa.
Trial design
High risk PCa is defined as newly diagnosed N+M0 disease (>4 radiologic pathologic pelvic lymph nodes), Gleason score ≥4 + 3=7, ≥cT2c and any PSA, with an indication for (pelvic) RT and ADT. Pts are treated with ADT (28 mo), Image-guided Arc Therapy on the primary tumour (77 Gy in 35 fractions) and weekly ModraDoc006/r for 7 (Part 1A) or 18 weeks (Part 1B). Sampling for PK of ModraDoc006/r, measured by a validated liquid chromatography with tandem mass spectrometry assay, is done up to 48h after intake. Adverse events (AEs) are evaluated with the National Cancer Institute’s Common Terminology Criteria for AEs and RT Oncology Group/European Organization for Research and Treatment of Cancer scale. Efficacy is assessed by Prostate Specific Antigen and Magnetic Resonance Imaging. In Part 1A, three dose levels are investigated. Dose-escalation is based on acute (within 3 mo) and late (within 12 mo) dose limiting toxicities (DLTs), evaluated in a Time-to-Event Continual Reassessment Method model. The MTD is the highest dose at which ≤15% of ≥ 6 pts experience DLTs. The number of pts is currently 19 in Part 1A and will be ≥ 9 in Part 1B.
Clinical trial identification
NCT03066154.
Editorial acknowledgement
Legal entity responsible for the study
Netherlands Cancer Institute - Antoni van Leeuwenhoek (NKI-AVL).
Funding
Netherlands Cancer Institute - Antoni van Leeuwenhoek (NKI-AVL).
Disclosure
J.H. Beijnen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Modra Pharmaceuticals B.V. All other authors have declared no conflicts of interest.
Resources from the same session
4634 - Comparative molecular analyses between microsatellite stable BRAFV600E mutant colorectal cancers and BRAFV600E mutant melanomas.
Presenter: Mohamed Salem
Session: Poster Display session 3
Resources:
Abstract
3264 - A novel preclinical model of RAF-independent MEK1 mutant tumors and its treatment with novel ATP competitive MEK inhibitor
Presenter: Luca Hegedus
Session: Poster Display session 3
Resources:
Abstract
4918 - HER2 inhibition in Aggressive Squamous Cell Carcinomas driven by a common MET Sema Domain Polymorphism
Presenter: Nur Afiqah Mohamed Salleh
Session: Poster Display session 3
Resources:
Abstract
2426 - ADAM9 as a target for lung cancer treatment
Presenter: Yuh-pyng Sher
Session: Poster Display session 3
Resources:
Abstract
5537 - Novel polyurea/polyurethane nanocapsules loaded with a tambjamine analog to improve cancer chemotherapy delivery and safety in lung cancer
Presenter: Marta Perez Hernandez
Session: Poster Display session 3
Resources:
Abstract
1597 - Discovery of Clinical Candidate DBPR112, a Furanopyrimidine-based Epidermal Growth Factor Receptor Inhibitor for the Treatment of Non-Small Cell Lung Cancer
Presenter: Hsing-pang Hsieh
Session: Poster Display session 3
Resources:
Abstract
3543 - Molecular characteristics in lung squamous cell carcinomas dependent on TP53 status – putative targets
Presenter: Vilde Haakensen
Session: Poster Display session 3
Resources:
Abstract
4111 - Comparison of molecular profiles between primary tumour and matched metastasis in non-small cell lung cancer
Presenter: Asuka Kawachi
Session: Poster Display session 3
Resources:
Abstract
4559 - Treatment with BLU-667, a potent and selective RET inhibitor, provides rapid clearance of ctDNA in Patients with RET-altered Non-Small Cell Lung Cancer (NSCLC) and Thyroid Cancer
Presenter: Giuseppe Curigliano
Session: Poster Display session 3
Resources:
Abstract
2501 - Triple MET/SRC/PIM inhibition in MET addicted tumors
Presenter: Ilaria Attili
Session: Poster Display session 3
Resources:
Abstract