Trial Information

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

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).