Sunitinib® in Patients With Recurrent Ovarian Clear Cell Carcinoma
Condition: Ovarian Cancer; Adverse Effects
MeSH terms: Carcinoma; Ovarian Neoplasms; Adenomyoepithelioma; Adenocarcinoma, Clear Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      Patients with early and advanced stages of epithelial ovarian cancer are treated with
      postoperative systemic chemotherapy after appropriate surgical staging and cytoreductive
      surgery. For ovarian cancer patients with recurrence, salvage chemotherapy with or without
      secondary cytoreductive surgery are recommended. The recommendation for specific primary
      adjuvant or salvage chemotherapy is cyclophosphamide or paclitaxel plus platinum regimens.
      Despite the high objective response rate associated with primary chemotherapy in ovarian
      cancer, the majority of patients will eventually experience disease recurrence and be
      potential candidates for a second-line treatment approach.

      Ovarian clear cell adenocarcinoma (OCCA) is recognized as a distinct histological type of
      cancer in the WHO-classification of ovarian tumors. OCCA is thought to arise from
      endometriosis and most patients present with the disease at early stages (International
      Federation of Gynecology and Obstetrics (FIGO) stages I and II). The incidence of OCCA among
      epithelial ovarian cancers is estimated to be less than 5-10%. However, OCCA occurs more
      frequent in Japan and Taiwan (around 10-15%). Unfortunately, OCCA is usually more resistant
      to systemic chemotherapy than other types and has a poorer prognosis.

      Sunitinib is a small molecule with anti-tumor properties pharmacologically mediated through
      inhibition of multiple receptor tyrosine kinase (RTKs), which are important regulators of
      tumor cell growth, angiogenesis, and metastasis. Due to its multi-targeted profile, the
      pharmacological activity of sunitinib is likely mediated by inhibition of multiple RTK
      targets and multiple pathways. c-KIT has been implicated in mastocytosis/mast cell leukemia,
      germ cell cancers, small-cell lung cancer, GISTs, AML, neuroblastoma, melanoma, and ovarian
      and breast carcinoma. In addition, sunitinib has demonstrated a higher response rate than
      that reported for anti- VEGF antibody treatment in patients with renal cell carcinoma (RCC).
      A few clinical case reports indicated sunitinib is effective in treating recurrent ovarian
      clear cell adenocarcinoma (OCCA) which is almost resistant to second line chemotherapy.

      So we would like to conduct this Phase II Sunitinib clinical trial in recurrent / persistent
      ovarian clear cell cancer patients.
    

Detailed description: 
      Ovarian cancer is the 10th leading cancer in women in Taiwan. There were 894 new cases in
      2004 and 297 women died of ovarian cancer in 2001 according to the data released by the
      Department of Health. The incidence of epithelial ovarian cancer increases with age and the
      median age at the time of diagnosis is 63 years, and 70% of patients present with advanced
      disease.

      Primary treatment for ovarian cancer consists of appropriate surgical staging and
      cytoreductive surgery, followed in most patients by systemic chemotherapy. Initial surgery
      should be a comprehensive staging laparotomy. For patients with clinical stage III or IV
      disease, the usual recommendation continues to be maximally cytoreductive surgery followed by
      adjuvant chemotherapy.

      Most patients with epithelial ovarian cancer will receive postoperative systemic
      chemotherapy. Observation is recommended for stage Ia, grade 1 tumors, owing to their high
      cure rate. For patients with higher-grade and/or higher-stage tumors, systemic chemotherapy
      is indicated. The recommendation for specific primary chemotherapy/primary adjuvant therapy
      is Paclitaxel plus platinum regimens. Paclitaxel plus cisplatin or carboplatin are the
      recommended regimens. The extent of treatment varies with stage of disease. For patients with
      advanced-stage disease, six cycles of chemotherapy are recommended, whereas for earlier-stage
      disease, three to six cycles are recommended, pending the results of ongoing studies in this
      group of patients.

      Treatment of relapsed ovarian cancer Despite the high objective response rate associated with
      primary platinum/taxane-based chemotherapy in advanced ovarian cancer, the majority of
      patients will eventually experience disease recurrence and be potential candidates for a
      second-line treatment approach. Treatment options for relapsed cancer are numerous. Patients
      with platinum-sensitive tumors (response to initial platinum therapy with no relapse for at
      least 6 months) may be retreated with platinum agents and/or taxanes upon relapse.

      Clear cell carcinomas of the ovary comprise approximately 5% of all ovarian neoplasms and
      exhibit unique features including a more aggressive clinical course and more malignant
      behavior. Clinically, clear cell carcinomas often present as a large pelvic mass, the
      majority of which are detected at an early stage (FIGO stage I). Despite the early stage
      diagnosis, survival rates are significantly lower for women with clear cell carcinoma
      relative to stage-matched serous adenocarcinoma of the ovary. Furthermore, tumors are more
      chemoresistant, resulting in a high degree of recurrence and exhibit more frequent early
      metastasis to lymph nodes and parenchymal organs.

      Sunitinib is a small molecule with anti-tumor properties pharmacologically mediated through
      inhibition of multiple receptor tyrosine kinase (RTKs), which are important regulators of
      tumor cell growth, angiogenesis, and metastasis. Specifically, sunitinib is a potent
      ATP-competitive inhibitor of the catalytic activity of a group of closely related RTKs
      consisting of VEGFR-1, -2, and -3, PDGFR-α and -β, KIT, CSF-1R, FLT-3, and RET. Due to its
      multi-targeted profile, the pharmacological activity of sunitinib is likely mediated by
      inhibition of multiple RTK targets and multiple pathways.

      In this study, we would like to evaluated the effect of Sunitinib in recurrent / persisted
      ovarian clear cell carcinoma.
    

Intervention name(s): Sunitinib
Intervention type(s): Drug
Intervention description(s): 37.5mg everyday from D1-D28
Other intervention name(s): Sutent
Intervention MeSH terms: Sunitinib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Sunitinib; recurrent ovarian cancer; clear cell carcinoma