Trial of Trientine Plus Pegylated Liposomal Doxorubicin and Carboplatin in Epithelial Ovarian Cancer
Condition: Ovarian Neoplasms Malignant (Excl Germ Cell); Peritoneal Carcinoma; Fallopian Tube Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Epithelial ovarian cancer (EOC) is the leading cause of gynecological malignancy-related
      deaths worldwide and is a substantial health threat to women. Many patients eventually
      develop chemoresistant relapsed disease and die despite surgery and combination chemotherapy.
      Progress in improving the survival in EOC has been slow, despite significant advances in
      treatment over the past 25 years. Tubal cancer and peritoneal cancer are thought to be
      similar in their origin, characteristics and treatment strategies. Based upon basic and
      animal studies, it is thought that copper chelators overcome platinum resistance. Thus,
      Trientine combined with carboplatin has been used to treat human cancers. The adverse effects
      (AEs) are acceptable in previously heavily-treated recurrent ovarian cancer patients,
      however, the treatment responses are limited. Therefore, here the investigators conduct a
      phase I trial of Trientine®, pegylated doxorubicin and carboplatin to find the dose-limited
      toxicities, and maximal toxicity dosage, and to explore whether the combination is applicable
      in epithelial ovarian, tubal and peritoneal cancers.
    

Detailed description: 
      Epithelial ovarian cancer, tubal, primary peritoneal cancers are lethal gynecologic
      malignances, with a 5-year survival rate below 25% for patients diagnosed with stage III-IV.
      Most advanced stage patients respond to cytoreductive surgery and platinum-based
      chemotherapy; however, >70% of women relapse, and platinum-resistant EOC is uniformly fatal.
      Physicians often increase the dosage of cytotoxic agents, or use single or combination
      second-line agents to overcome the drug resistance. Nevertheless, second-line chemotherapy
      sometimes may not achieve the expected cytotoxic effect and drug resistance may lead to
      cancer-specific death. Overcoming resistance is an important strategy for improving the
      therapeutic efficacy in cisplatin-containing cancer chemotherapy.

      Cu homeostasis in human cells involves the inter-regulatory circuitry composed of Cu, the
      high-affinity Cu transporter (hCtr1) and transcription factor Sp1. Human copper transporter 1
      (htr1) in humans are also involved in the import of antitumor agent cisplatin (Cp). Earlier
      the investigators also discovered that the magnitude of hCtr1 expression by Cu chelators
      depends upon the basal levels of hCtr1 expression, and that high levels of hCtr1 expression
      can be modulated through Cu deprivation in Cp-resistant (CpR) cells, providing a molecular
      basis for the development of Cu chelators as Cp resistance reversal agents in the clinical
      settings. D-penicillamine and Cp act synergistically to inhibit tumor growth. The
      investigators conduct this trial with combination agents, including LipoDox®, carboplatin and
      Trientine®, to develop the clinical application of copper chelator in conjunction with
      cytotoxic agents to conquer platinum-resistance. This trial is practical and is of
      perspective.
    

Intervention name(s): trientine dihydrochloride; pegylated liposomal doxorubicin; carboplatin
Intervention type(s): Drug; Drug; Drug
Intervention description(s): trientine dihydrochloride 300MG/CAPSUE PO daily (in different dose levels); pegylated liposomal doxorubicin 40mg/m2 IV D1; carboplatin AUC 4 IV D1
Other intervention name(s): pegylated liposomal doxorubicin; carboplatin; trientine dihydrochloride; carboplatin; trientine dihydrochloride; pegylated liposomal doxorubicin
Intervention MeSH terms: Carboplatin; Doxorubicin; Liposomal doxorubicin; Trientine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Copper chelator; Epithelial ovarian cancer; Tubal cancer; Peritoneal cancer; Trientine; Pegylated liposomal doxorubicin; Carboplatin