Targeted Radiation Therapy for Ovarian Cancer: Intraperitoneal Treatment With 211-astatine-MX35 F(ab')2
Condition: Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Study type: Interventional
Phase: Early Phase 1

Summary: 
      In this alpha-radioimmunotherapy study groups of 3 patients with recurring epithelial ovarian
      cancer treated by salvage chemo-therapy and being in complete or good partial remission will
      receive one intra peritoneal infusion of 211 astatine (211At)-MX35 F(ab')2 . Patients will
      receive a single dose of MX35 F(ab')2 radiolabeled with increasing activity concentration of
      211At in 1.0 - 2 L Extraneal® solution starting at an activity concentration of 50
      megabecquerel per litre (MBq/L).
    

Detailed description: 
      -  Five days prior to therapy the patient is provided with a central intra venous line and
           an abdominal catheter will be introduced during laparoscopy. To investigate the access
           to the whole abdominal cavity and possible catheter leakage, a 99mTc-colloid, will be
           infused intra peritoneally (IP) within 1.0 L of a gluco-polymer (Extraneal®).

        -  At the day of treatment vital signs will be measured prior to and after the 30 min
           infusion and at least every second hour during the first 6 hours after infusion, daily
           for the remainder of the in-hospital stay and at a minimum at 2, 3, 4 and 8 weeks after
           the IP infusion. Blood samples will be obtained for pharmacokinetic analyses every hour
           after completion of the IP infusion for 8 hours, then every 6 hours, together with
           sampling from the i.p. catheter.

        -  SPECT imaging of the whole abdominal cavity and thorax including the thyroid may be
           performed following completion of the IP infusion and at approx 8 or 20hrs post
           infusion.

        -  Physical examination and electrocardiogram will be done prior to and 4 weeks after the
           IP infusion. Clinical biochemical and hematological parameters will be monitored weekly
           after treatment. Blood samples to evaluate immunogenicity as well as cancer antigen-125
           (CA-125) will also be taken at 2 and 8 weeks after treatment.

        -  The first patient will be observed for at least 4 weeks with any observed toxicity is
           Grade 2 or less, before the additional patient is accrued at the dose level.

        -  Dosimetry safety criteria: Based upon published data on maximal tolerated absorbed dose
           (Gy) recalculated to equivalent dose (Sv) with the assumption that the relative
           biological effectiveness (RBE) = 5, a limit for organ doses is defined. If any organ
           would reach the defined limit the study will be stopped.
    

Intervention name(s): 211-astatine MX35 F(ab')2
Intervention type(s): Combination Product
Intervention description(s): Alpha emitting radionuclide 211At conjugated to monoclonal antibody MX35 F(ab')2. Targeting the sodium phosphate transporter (NaPi2b).
Intervention model: Sequential Assignment
Intervention model description: To investigate the pharmacokinetics of the conjugate 211At-MX35 F(ab') 2.
Groups of 3 patients will be treated at increasing activity concentrations starting at 50 MBq/L
Masking: None (Open Label)
Primary purpose: Treatment