Phase II and Pharmacokinetic Study of Avastin and Doxil in the Treatment of Platinum-resistant or Refractory Ovarian Cancer
This study registration at clinicaltrials.gov is divided into 2 records. This record
(NCT00846612) is for pharmacokinetics of Doxil. Another record (NCT00945139) describes the
efficacy and safety of the combination treatment.
Treatment upon diagnosis of epithelial ovarian cancer (EOC) consists of surgery to achieve
maximal tumor debulking followed by platinum-based chemotherapy (carboplatin + paclitaxel).
Recently, optimally (e.g., < 1 cm residual disease) debulked patients appear to benefit from
regimens that include intraperitoneal administration of cisplatin. While complete response
(CR) is frequently achieved, by two years 50% of the patients show signs of recurrence.
When EOC presenting at an advanced stage recurs, even after a CR had been achieved, it can
no longer be totally eradicated. Nevertheless, a number of drugs lead to objective
responses, patients benefit with a prolongation of survival. Anti-tumor activity of Doxil
against ovarian cancer was noted in a phase I study, and this was followed by a phase II
study that demonstrated activity in platinum and paclitaxel refractory disease. In the
expanded phase II experience at the University of Southern California, responses to Doxil
occurred preferably in disease that was not bulky and after fewer prior treatments.
Typically, several cycles were required for maximum response, and some patients had
prolonged stable disease. Subsequently, the study of Gordon et al established the preferred
role of this drug formulation in the 2nd line-setting. It is logical, therefore, to build
on this agent in trying to improve the outcome of patients with recurrent ovarian cancer,
and in particular, to consider a combination with Avastin, since Avastin has shown agent
activity in retrospective data and recent studies in EOC.
A combination of Doxil with Avastin has several aspects of interest to ovarian cancer
treatment: 1) independent single-agent activity, 2) enhanced localization of Doxil is
possible via increased half-life (if liposomal egress is diminished) and decreased tumoral
interstitial pressure, 3) improved Doxil distribution, and 4) likely favorable toxicity
profile since Doxil's only common problematic toxicity is to the skin (palmar-plantar
erythrodysesthesia or PPE). Pharmacokinetic issues will be addressed in selected patients,
by comparing cycle 1 (without Avastin) with cycle 2 (with Avastin).
Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
change in peak plasma concentration of Doxil without and with Avastin
In cycle 1, patients were treated only with Doxil; in cycle 2, patients were treated with Doxil and Avastin.
1 hour, 1, 4, 7, 10, 14, and 21 days post-dose in cycle 1 and cycle 2
Franco Muggia, MD
New York University School of Medicine
United States: Institutional Review Board
|Bellevue Hospital||New York, New York 10016|
|NYU Cancer Center||New York, New York 10016|
|Univ. of New Mexico cancer research and treatment center||Albuquerque, New Mexico 87131|
|NYU medical center (Tisch Hospital)||New York, New York 10016|