NCT01246440

Catumaxomab as a Consolidation Therapy in Patients With Ovarian Cancer in Second or Third Clinical Disease Remission

A Phase II of Intraperitoneal Catumaxomab as a Consolidation Therapy in Patients With Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma in Second or Third Complete Clinical Disease Remission

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 39 (actual)
• Sponsor: Grupo Español de Investigación en Cáncer de Ovario · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the efficacy and safety of catumaxomab as consolidation treatment in patients with epithelial ovarian cancer in second or third complete remission.

Detailed description

Epithelial ovarian cancer is the most lethal malignant gynecological tumor and the fourth most common cause of death by cancer among women. The highest incidence rates are observed in Eastern and Northern Europe, and in the United Status. In Spain, 3,262 new cases were diagnosed in 2002, and the figure is expected to rise to 3,722 cases in 2015 (Globocan 2002, International Agency for Research on Cancer -IARC). The majority of patients with ovarian cancer are diagnosed at an advanced stage, and are treated with maximum cytoreductive surgery followed by intraperitoneal and/or intravenous chemotherapy. What is considered standard chemotherapy consists of a platinum (carboplatin or cisplatin) combined with a taxane, usually paclitaxel (Ozols, 2003; Armstrong 2006). Although many patients respond to the initial treatment, the majority experience subsequent recurrence of the disease, which is why they need to be treated with successive salvage therapies in an attempt to control the disease until it is converted into totally refractory (Markman, 2004). Only 20-30% of patients can be cured with current treatments, which is why it is necessary to investigate and develop new treatments and/or treatment strategies (Yap, 2009). Although with the initial treatment based on cytoreductive surgery and platinum-based chemotherapy the large majority of patients achieve complete remission of the disease, 90% of the patients with sub-optimum cytoreductive surgery and 70% with optimum cytoreductive surgery develop a recurrence in the first 24 months. One of the treatment strategies being investigated to try and improve the results is the administration of consolidation or maintenance treatment to those patients that have achieved a complete response of their disease to reduce the risk of subsequent recurrence (Sabbatini, 2006). In the last few years, various studies have established that investigating a possible therapeutic effect of consolidation or maintenance treatment following second or third complete clinical remission, obtained with a salvage chemotherapy, produces several advantages over the same strategy applied on a first complete clinical response: the median of progression-free survival after second or third complete response is shorter and more predictable -10 months-, and moreover the recurrence is practically universal (Markman 2004; Harrison, 2007; Levine, 2007; Markman, 2008; Juretza, 2008). Catumaxomab has proven to be effective in patients with refractory tumours and recurring malignant ascites, i.e. patients with a very advanced disease, a large tumour and no treatment options. These clinical conditions are the worst for researching into any immune-based therapy, hence it seems logical to study the efficacy of catumaxomab in more favourable conditions. Patients with ovarian cancer in second or third complete remission may be a more suitable population for investigating the intraperitoneal administration of catumaxomab as consolidation treatment: 1. 100% of the epithelial ovarian cancers express EpCAM (Epithelial cell adhesion molecule )(Kim, 2003; Bellone, 2009). 2. These patients present a minimal residual disease that cannot be eliminated with standard chemotherapy and is responsible for a subsequent recurrence in practically every patient, with a median progression-free survival of 10 months (Markman, 2004; Harrison, 2007). 3. The peritoneal cavity is a very common location for residual disease and/or recurrence in ovarian cancer (Ferrandina, 2006). 4. The absence of macroscopic disease in the peritoneal cavity may bring about a greater absorption of catumaxomab on the blood level, with a hypothetical greater efficacy on the systemic level without entailing a greater risk of toxicity (Heiss, 2008; Lordick, 2008). The intention in this phase II study is to estimate the clinical benefit of consolidation treatment with catumaxomab in patients with epithelial ovarian cancer in second or third complete remission, by measuring progression-free survival, the percentage of progression-free patients at 12, 18 and 24 months, and comparing individually for each patient the duration of progression-free survival obtained following consolidation with catumaxomab with that observed in her first complete remission. If we observe a median of progression-free survival equal to or greater than 14 months, accompanied by a significant percentage of progression-free patients at 18 and 24 months, we will assess the possibility of subsequently designing a phase III study of consolidation with catumaxomab. To improve the tolerability of catumaxomab, premedication will be administered with low-dose corticoids before each infusion of catumaxomab. The low doses of corticoids have been shown not to interfere with the efficacy of catumaxomab, but by reducing the release of certain cytokines like TNF-α (Tumor Necrosis Factor Alpha) they may reduce the associated adverse effects (Waltz, 2005).

Conditions

• Ovarian Cancer

Interventions

Type	Name	Description
DRUG	Catumaxomab	Catumaxomab: 4 intraperitoneal infusions of catumaxomab over 11 days administered in a period of 3 hours through an intraperitoneal catheter with the following dosage: 1) 10 µg on Day 0. 2) 20 µg on Day 3. 3) 50 µg on Day 7. 4) 200 µg on Day 10.

Timeline

• Start date: 2010-06-01
• Primary completion: 2014-02-01
• Completion: 2014-12-01
• First posted: 2010-11-23
• Last updated: 2016-08-11

Locations

17 sites across 1 country: Spain