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Original research
CINOVA: a phase II study of CPC634 (nanoparticulate docetaxel) in patients with platinum resistant recurrent ovarian cancer
  1. Ingrid Boere1,
  2. Ignace Vergote2,
  3. Rob Hanssen3,
  4. Mathilde Jalving4,
  5. Christine Gennigens5,
  6. Petronella Ottevanger6,
  7. Yes J van de Wouw7,
  8. Cristianne J F Rijcken3,
  9. Ron H J Mathijssen1 and
  10. Jonathan Ledermann8
  1. 1Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
  2. 2Division of Gynaecological Oncology, Leuven Cancer Institute, Department of Gynaecology and Obstetrics, Universitaire Ziekenhuizen Leuven, Katholieke Universiteit Leuven, Leuven, Belgium
  3. 3Cristal Therapeutics, Maastricht, The Netherlands
  4. 4Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  5. 5Department of Medical Oncology, CHU de Liège, Liège, Belgium
  6. 6Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands
  7. 7Department of Internal Medicine, VieCuri Medical Centre, Venlo, The Netherlands
  8. 8Department of Oncology, University College London (UCL) Cancer Institute, UCL & UCL Hospitals Comprehensive Biomedical Research Centre, London, UK
  1. Correspondence to Dr Ingrid Boere, Cancer Institute Department of Medical Oncology, Erasmus MC, Rotterdam, Zuid-Holland, The Netherlands; i.boere{at}erasmusmc.nl

Abstract

Objective Recurrent platinum-resistant ovarian cancer has a poor prognosis with limited therapeutic options. Sub‐therapeutic intra-tumoral drug concentrations may add to therapy resistance. CPC634 (docetaxel entrapped in CriPec nanoparticles) was designed to enhance tumor accumulation of drug with localized drug release at the target site to increase therapeutic efficacy. This study investigated the therapeutic effect of CPC634 in patients with platinum-resistant ovarian cancer.

Methods According to a Simon 2-stage design trial, the first stage included 13 patients, and 12 patients were enrolled in the second stage. Eligible patients had measurable disease and had progressed ≤6 months after the last platinum-based therapy. Platinum-refractory disease was excluded. In stage 1, the number of previous treatment lines was unlimited; in the second stage, a maximum of two prior lines altogether were allowed. The primary endpoint was the objective response rate by Response Evaluation Criteria in Solid Tumor (RECIST) V1.1. Secondary endpoints included safety, progression-free survival at 6 months, cancer antigen 125 (CA125) response, and disease control rate.

Results The patients’ median age was 66 years (range 22–77) and most were International Federation of Gynecology and Obstetrics (FIGO) stage III (56%). The median number of previous treatment lines was 3 (range 3–5) in stage I and 2 (range 1–4) in stage II of the study. None of the patients had an objective response, one patient had a CA125 response (5%), and seven patients had stable disease at first evaluation (35%). Median progression-free survival was 1.4 months in stage 1 and 3.0 months in stage 2. Adverse events (all grades) were mainly gastrointestinal in 24 patients (96%), fatigue in 11 (44%), dyspnea in 10 (40%), and infections in 10 (40%) of patients. Grade 3 or higher adverse events occurred in 14 patients (36%), including gastrointestinal in 4 (16%), anemia in 3 (12%), and febrile neutropenia, fatigue, chronic kidney disease, dehydration, and hypertension each in 1 (4%) patient. The trial was stopped prematurely due to futility.

Conclusions Treatment with CPC634 was feasible, but without apparent clinical activity in patients with recurrent platinum-resistant ovarian cancer. Side effects were mainly gastrointestinal in 24 (96%) patients, including nausea, vomiting, and decreased appetite, fatigue, anemia, and dyspnea.

  • Ovarian Cancer
  • Cystadenocarcinoma, Serous

Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

http://dx.doi.org/10.1136/ijgc-2023-004308

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    Data availability statement

    Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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    Footnotes

    • Contributors Conception and design: CJFR, RH, RHJM, JL, IV. Development of methodology: CJFR, RH, RHJM, JL, IV. Acquisition of data (acquired and managed patients, provided facilities, etc): IB, IV, MJ, CG, PO, YJvdW, RHJM, JL. Analysis and interpretation of data (eg, statistical analysis, biostatistics, computational analysis): IB, IV, RHJM, CJFR, JL. Writing, review, and/or revision of the manuscript: IB, IV, MJ, CG, PO, YJvdW, RHJM, CJFR, JL. Administrative, technical, or material support (ie, reporting or organizing data, constructing databases): CJFR. Study supervision: RHJM, JL. Other (providing medication CPC634): RH.

      Responsible for the overall content as guarantor: IB

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests CJFR was employee and is meanwhile paid consultant for Cristal Therapeutics, while RH was employed till August 2021 by Cristal Therapeutics.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.