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
5389 - Two-weekly accelerated BEP (aBEP) regimen as induction chemotherapy (CT) in intermediate and poor prognosis patients (pts) with nonseminomatous germ cell tumors (NSGCT): final results of phase II trial.
Presenter: Alexey Tryakin
Session: Poster Display session 3
Resources:
Abstract
2934 - Differential expression of circulating miR375 and miR371 to detect teratoma and viable germ cell malignancy
Presenter: Lucia Nappi
Session: Poster Display session 3
Resources:
Abstract
3585 - Prognosis of anaemia in disseminated testicular germ cell tumours. On behalf of the Spanish Germ Cell Cancer Group (SGCCG)
Presenter: Esmeralda Garcia Torralba
Session: Poster Display session 3
Resources:
Abstract
2254 - The Effects Of Primary Testicular Tumor Localization On Prognosis In Patients With Nonseminomatous Testis Cancer
Presenter: Birol Yildiz
Session: Poster Display session 3
Resources:
Abstract
4505 - Initial Results of a Phase II study of Nivolumab and Ipilimumab in Metastatic Adrenal Tumors.
Presenter: Matthew Campbell
Session: Poster Display session 3
Resources:
Abstract
3369 - NEMIO: a randomized phase II trial evaluating efficacy and safety of dose dense MVAC (ddMVAC) + durvalumab +/- tremelimumab as neoadjuvant treatment in patients with bladder muscle-invasive urothelial carcinoma
Presenter: Constance Thibault
Session: Poster Display session 3
Resources:
Abstract
2075 - KEYNOTE-866: Phase 3 Study of Perioperative Pembrolizumab (pembro) or Placebo (pbo) in Combination With Neoadjuvant Chemotherapy in Cisplatin (cis)-Eligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
4824 - KEYNOTE-905: A Phase 3 Study of Cystectomy Plus Perioperative Pembrolizumab Versus Cystectomy Alone in Cisplatin (cis)-Ineligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Matthew Galsky
Session: Poster Display session 3
Resources:
Abstract
2253 - Phase 3 LEAP-011 trial: First-Line Pembrolizumab With Lenvatinib in Patients With Advanced Urothelial Carcinoma Ineligible to Receive Platinum-Based Chemotherapy
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
4310 - PULSE : A Single Arm Trial Assessing The Activity and Safety of Avelumab Immunotherapy Maintenance among Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma (mSCPC).
Presenter: Noemie Gassian
Session: Poster Display session 3
Resources:
Abstract