Pazopanib with Topotecan weekly for patients with platinum-resistant or intermediate-sensitive recurrent ovarian cancer: results - TOPAZ - multicentre, open label phase I/II study

Sep 24, 2026

The investigator-initiated phase I/II trial evaluated Topotecan combined with Pazopanib in platinum-resistant or intermediate-sensitive recurrent ovarian cancer (ROC), aiming to assess safety, tolerability, and clinical activity. Patients with first or second recurrence were enrolled in a multicentre open-label design. Phase I determined the maximum tolerated dose by dose escalation, and phase II evaluated safety and efficacy. Maintenance Pazopanib was allowed for patients in clinical remission until progression. Overall response was 16% and the clinical benefit rate reached 68%.

LanguageEnglish

CategoryHealthcare

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Abstract

Purpose

Methods

Results

Conclusion

Introduction

Background and unmet need in recurrent ovarian cancer

Prior antiangiogenic and targeted therapy evidence

Study rationale and related clinical trials

Journal of Cancer Research and Clinical Oncology (2023) 149:7637–7649 [https://doi.org/10.1007/s00432-023-04647-9](https://doi.org/10.1007/s00432-023-04647-9) Pazopanib with Topotecan weekly for patients with platinum‑resistant or intermediate‑sensitive recurrent ovarian cancer: results of a multicentre, open label phase I/II study (TOPAZ) Radoslav Chekerov1 · Tjadina Arndt1 · Klaus Pietzner1 · Ulrich Canzler2 · Pauline Wimberger2 · Hans‑Georg Strauß3 · Sven Mahner4 · Linn Woelber5 · Nikolaus de Gregorio6 · Gertraud Stocker7 · Ekkehard von Abel8 · Tanja Neunhoeffer9 · Antje Kristina Belau10 · Alexander Mustea11 · IsilYalinkaya1 · Elena Ioana Braicu1 · Rolf Richter1 · Jalid Sehouli1 · for the NOGGO ovarian cancer study group Received: 23 December 2022 / Accepted: 9 February 2023 / Published online: 31 March 2023 © The Author(s) 2023 Abstract Purpose Pazopanib has promising antiangiogenetic activity in solid cancers. The investigator-initiated phase I/II trial evaluated the combination of Topotecan with Pazopanib in platinum-resistant or intermediate-sensitive recurrent ovarian cancer (ROC) . Methods Patients (≥ 18 years) with first or second recurrence were enrolled in this multicentre open-label trial. Phase I analysed Topotecan 4 mg/m2 (day 1, 8, 15, ever 28 days) for six cycles to identify the maximum tolerated dose (MTD) of Pazopanib added in a dose-escalating scheme with 400 mg starting dose. The phase II analysed safety and efficacy aspects. For all patients with clinical remission a maintenance with Pazopanib until progression was allowed. This trial is registered [with ClinicalTrials.gov](with ClinicalTrials.gov), number NCT 01600573. Results Between June 2012 and February 2017, 11 patients were enrolled in the phase I, and 50 patients in the phase II study. The MTD of Pazopanib was determined by 400 mg/daily. Haematological and liver toxicities determined the dose limiting toxicities (DLT) and the most common grade 3–4 adverse events: leucopenia (25%), neutropenia (22%), thrombocytopenia (19%), accumulation of cholestatic (20%) and hepatocellular damage (15%), which often caused dose modifications, but no new life-threatening events. Overall response was 16% and clinical benefit rate 68%. Median progression-free survival (PFS) was 3.5 months (95% CI 2.0—5.0) . Due to early progression only 20% of the patients were able to start with maintenance treatment. Conclusion The combination of pazopanib and weekly topotecan is feasible, resulting in a manageable haematological and liver toxicity, but despite its encouraging response rate, was not associated with a significant survival benefit. Keywords Platinum-resistant ovarian cancer · Topotecan · Pazopanib | Radoslav Chekerov and Tjadina Arndt contributed equally to this study. | | --- | | Cancer Study Group is lisited in acknowledgements | * Radoslav Chekerov[radoslav.chekerov@charite.de](radoslav.chekerov@charite.de) Extended author information available on the last page of the article Introduction Epithelial ovarian cancer remains the gynaecological malignancy with the highest mortality being the seventh most common cancer in women worldwide (Sung et al. 2021) . Despite the progress in surgical and systemic treatment with implementation of anti-angiogenetic and poly (ADP-ribose) polymerase (PARP) inhibitors, more than 75% of all patients will progress with development of multidrug-resistance disease (Colombo 2019 ; Bois et al. 2009) . Recurrent ovarian cancer becomes a palliative character with generally less standardised treatment options dependent on the treatmentfree interval (TFI) to the last platinum chemotherapy and genetic features like BRCA mutation status. Especially for patients with short TFI of less than 6 months, where platinum seems not to be the best treatment option, the chance of remission remains low, which results in a particularly poor prognosis (Bois et al. 2009 ; Wilson et al. 2017) . Current treatment strategies a

FAQs

What was the main purpose of the TOPAZ phase I/II study?

To evaluate the combination of weekly Topotecan with Pazopanib in platinum-resistant or intermediate-sensitive recurrent ovarian cancer, focusing on safety and clinical activity.

How were doses and treatment phases structured in the trial?

Phase I used dose escalation of Pazopanib added to Topotecan over six cycles to identify the maximum tolerated dose, and phase II assessed safety and efficacy; patients with clinical remission could receive maintenance Pazopanib until progression.

What did the study find regarding safety and key toxicities?

Haematological and liver toxicities were dose-limiting, with the most common grade 3–4 adverse events including leucopenia, neutropenia, thrombocytopenia, and cholestatic/hepatocellular damage; these often required dose modifications and no new life-threatening events were reported.

Did the combination improve survival outcomes?

The combination was feasible and produced encouraging response rates, but it was not associated with a significant survival benefit; median progression-free survival was 3.5 months.

Sep 24, 2026

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