Karenitecin in Pediatric Patients With Refractory or Recurrent Solid Tumors N10010)
Condition: Solid Tumors
MeSH terms: Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a Phase 1, open-label, single-center, dose-escalating study in pediatric patients
      with refractory or recurrent solid tumors. Patients will be registered into 1 of 2 strata,
      depending upon the presence bone marrow metastases or previous treatment with intensive
      myelosuppression therapy. Patients will receive Karenitecin along with cyclophosphamide daily
      for 5 consecutive days, every 21 days (1 treatment cycle). Treatment may continue for up to
      20 cycles, as long as there is continued evidence of clinical benefit and an absence of
      unacceptable toxicity.
    

Detailed description: 
      This is a Phase 1, open-label, dose-escalating study of karenitecin plus cyclophosphamide in
      the treatment of pediatric patients with refractory or recurrent solid tumors. All patients
      must have histologically documented diagnosis of cancer (solid tumors) refractory to
      conventional therapeutic modalities or for which no curative treatment exists.

      Approximately 50 patients will be registered into the study in one of 2 strata.

      Stratum 1 will include patients with known bone marrow metastases or those who have had prior
      intensive myelosuppression therapy. Stratum 2 will include patients without previous
      intensive myelosuppressive therapy or bone marrow metastases. Each stratum will accrue
      patients independently.

      The primary endpoint in this study is the MTD and determining the recommended Phase 2 dose
      level for this study. The MTD will be determined for each stratum independently.

      There are 3 defined periods in this study:

      Period I (Screening and Registration)

      Period II (Active Treatment): An accelerated titration dose escalation design will be used in
      this study. Dose escalation will function independently for each stratum.

      Period III (End of Study): Once treatment has been discontinued, patients will undergo
      end-of-study procedures.
    

Intervention name(s): Kareniticin and cyclophosphamide
Intervention type(s): Drug
Intervention description(s): An accelerated titration dose escalation design will be used in this study. Dose escalation will function independently for each stratum. Patients in both strata will receive Karenitecin and cyclophosphamide administered as an IV infusion each day for 5 consecutive days. In addition, patients in Stratum 1 will receive prophylactic G-CSF starting 24 hours after completion of the fifth dose of Karenitecin and cyclophosphamide (and continuing daily until the ANC is over 1500/mm3 after nadir). The regimen will be repeated every 21 days (1 treatment cycle).
Treatment may continue for up to 20 cycles, provided there is continued evidence of clinical benefit and absence of unacceptable toxicity.
Intervention MeSH terms: Cyclophosphamide
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: solid tumors