Intravenously Administered Pegylated Liposomal Mitomycin-C Lipid-based Prodrug (PROMITIL) in Cancer Patients With Solid Tumors.
Condition: Cancer; Solid Tumor; Metastatic Colorectal Cancer (mCRC)
MeSH terms: Neoplasms; Colorectal Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a Phase I, multi-center, Dose-Escalating, Safety Study of an Intravenously
      Administered Pegylated Liposomal Mitomycin-C Lipid-based Prodrug (PL-MLP, PROMITIL) in Cancer
      Patients with Solid Tumors. The study comprised of:

      Escalated cohorts A-H: 27 male or female participants, ages 18-80, BMI 18-36 diagnosed with
      inoperable, recurrent or metastatic malignant solid tumors, deemed incurable, and who have
      failed to respond to standard therapy or for whom no standard therapy is available. Eligible
      subjects will be assigned, successively in order of accrual, to one of eight cohorts, to
      receive escalating doses of intravenously infused PROMITIL. PROMITIL will be administered as
      an intravenous infusion. Dose escalation will only proceed in the absence of dose-limiting
      toxicity (DLT). For this purpose, each cohort will only begin its first cycle of PROMITIL
      when the cohort preceding it has successfully completed its first 4-week cycle without any
      signs of DLT.

      Expanded cohort: 17 adult patients with metastatic CRC. The purpose of this expanded cohort
      is to further evaluate the safety of Promitil and to search for signs of antitumor activity
      of Promitil in this specific patient population.

      Combination Cohort (Promitil concomitantly with Capecitabine): 23 adult patients with
      metastatic CRC.

      Triple combination Cohort: 13 additional subjects with metastatic CRC, received combination
      of Promitil concomitantly with Bevacizumab (5 mg/kg) on day 1 of a 28 day cycle and
      Capecitabine on days 1-14 of a 28 day cycle.

      3 weekly cohort- 9 subjects with metastatic CRC will receive Promitil and Bevacizumab (7.5
      mg/kg) on day 1 of a 21 day cycle.
    

Detailed description: 
      For all cohorts, PROMITIL will be administered as an intravenous infusion at an initial rate
      of 0.25mg/min followed by gradual increase to a maximal rate of 2mg/min until completion of
      dosing, if absence of infusion reactions is established and in line with most updated version
      of IFU available for this study.

      For each subject, subsequent dosing will take place 28 days after the previous treatment,
      provided they are deemed fit to be dosed again.

      Patients will return to the study center on days 8, 15, 22 of cycle 1, and on day 15 of
      cycles 2 and 3, for monitoring assessments.

      All patients will be followed-up for survival and post-Promitil treatment. Patients who did
      not received 3 cycles of PROMITIL will be followed up only until PD.

      For the 3 weekly cohort Promitil will be administered at 3 week interval together with
      Bevacizumab (7.5 mg/kg). Patients will return to the study center on days 8 and 15 of cycle
      1, and on day 15 of cycles 2 and 3, for monitoring assessments.
    

Intervention name(s): Promitil; Capecitabine; Bevacizumab
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 2 mg/kg dose IV; 1000 mg dose BID PO for days 1-21 for Combination Cohort and on day 1-14 on Triple combination Cohort; for Triple combination cohort an IV dose of 5 mg/kg on day 1 at 4 week interval. For the 3 weekly cohort an IV dose of 7.5 mg/kg at 3 week interval.
Other intervention name(s): Xeloda; Avastin
Intervention MeSH terms: Bevacizumab; Capecitabine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: phase 1; dose escalating; prodrug; mitomycin C; Capecitabine