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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

Phase 2
18 Years
Open (Enrolling)
Ovarian Cancer

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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,

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).

Inclusion Criteria:

- Signed Informed consent.

- Initial histopathologic diagnosis of epithelial ovarian cancer, cancer of the
fallopian tube or primary peritoneal carcinoma

- Women ≥ 18 years

- ECOG performance status ≤ 1 (Eastern Cooperative Oncology Groupperformance)

- Initial surgical cytoreduction as primary treatment combinated with Platinum- based
chemotherapy administered as part of primary therapy.

Failure of the primary treatment as manifested by recurrent disease that have achieved a
second or third complete response with a second or third-line chemotherapy (platinum-based
or not).

The complete response to the second or third-line chemotherapy is defined as non symptoms
of cancer persistence, normal CA-125 (cancer antigen 125), negative medical examination,
and no evidence of disease in a TAC.

- At least 4 cycles of second or third-line chemotherapy must have been administered

- Surgery performed at first or second relapse in conjunction with second or third-line
chemotherapy is permitted.

Exclusion Criteria:

- Acute or chronic infection

- Concomitant treatment with cancer chemo- and/or radiotherapy

- Exposure to an investigational product within 28 days of first infusion

- Previous treatment with murine monoclonal antibodies

- Inadequate renal function: creatinine >1.5 upper limit of normal [ULN] and/ or
calculated creatinine clearance ≥ 50 mL/min

- Inadequate hepatic function (AST, ALT, >2.5 xULN; bilirubin >1.5 xULN),
Hypoalbuminaemia < 3 g/dL

- Platelets <80000 cells/mm3; absolute neutrophil count (ANC) <1000 cells/mm3,

- Hb < 8g/dL and PTT > 2 x ULN

- Patients with occlusive intestinal or symptomatic sub-occlusive intestinal within the
last 30 days.

- Significant cardiovascular disease including unstable angina or myocardial infarction
within 6 months before initiating study treatment or a history of ventricular

- Unable or unwilling to comply fully with the protocol.

- Any co-morbid disease that would increase risk of toxicity according to investigator

- Any kind of disorder that compromises the ability of the subject to give written
informed consent and/or comply with the study procedures

- Exposure to investigational product, cancer, chemo-or radiotherapy within the last 28
days (6 weeks for nitrosoureas or mitomycin C) before first infusion

- Known or suspected hypersensitivity to catumaxomab or similar antibodies

- Long-lasting steroid treatment (≥ 7 days), Patients should only be included after
stepwise discontinuation and free of steroids for a minimum of 5 days

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival (PFS)

Outcome Description:

Progression-free survival per protocol is defined as the period from the commencement of the consolidation treatment (catumaxomab Day 0) and the recurrence of the disease or the last follow-up for the patients not developing a recurrence.

Outcome Time Frame:

3 years

Safety Issue:


Principal Investigator

Ana Oaknin, Dra.

Investigator Role:

Study Chair

Investigator Affiliation:

Hospital de la Vall d'Hebron


Spain: Spanish Agency of Medicines

Study ID:




Start Date:

June 2010

Completion Date:

September 2013

Related Keywords:

  • Ovarian Cancer
  • Ovarian Neoplasms