Phase I/II Trial of Safety and Anti-tumor Efficacy of AXL1717(Picropodophyllin) in the Treatment of Recurrent Malignant Astrocytomas (AXL1717)
Recruitment status was: Recruiting
|Glioblastoma Gliosarcoma Anaplastic Astrocytoma Anaplastic Oligodendroglioma Anaplastic Oligoastrocytoma Anaplastic Ependymoma||Drug: AXL1717||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Clinical Trial of the Safety, Tolerability, and Anti-tumor Efficacy of the IGF-1R Inhibitor, AXL1717 (Picropodophyllin), in the Treatment of Recurrent Malignant Astrocytomas|
- Phase I - Determine recommended Phase II dose. [ Time Frame: 8 months ]To determine the recommended phase II dose (RPTD) of AXL1717 in recurrent malignant astrocytomas
- Phase II - Determine Antitumor effect [ Time Frame: 4 months ]To determine if AXL1717 has any antitumor effect as a single agent treatment in recurrent malignant astrocytomas by evaluating progression-free-survival (PFS) at 6-months.
- Phase I - Maximum Tolerated Dose (MTD) [ Time Frame: 8 months ]To identify the MTD of AXL1717.
- Phase I - Molecular markers of optimum response [ Time Frame: 8 months ]To assess potential molecular markers that might predict optimum response sub-population groups
- Phase I - Molecular Markers of IGF (insulin like growth factor)-1R pathway [ Time Frame: 8 months ]To evaluate surrogate molecular markers of IGF-1R pathway activation/inhibition after treatment with AXL1717 in patients with malignant astrocytomas
- Phase II - Time-To-Progression (TTP) and Overall Survival (OS) [ Time Frame: 4 months ]To determine time-to-progression (TTP) and overall survival (OS) of patients treated with AXL1717
- Phase II - Overall Response Rate [ Time Frame: 4 months ]To assess overall response rate (ORR) in recurrent malignant astrocytomas after treatment with AXL1717
- Phase II - Imaging Evidence of Response. [ Time Frame: 4 months ]To identify surrogate imaging evidence of response on MRI (magnetic resonance imaging)sequences by RANO criteria (with additional special attention to T2-FLAIR, DWI (diffusion-weighted imaging), perfusion MRI and multi-voxel MRS (magnetic resonance spectroscopy) sequences).
|Study Start Date:||December 2012|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
In the first phase, 10-20 patients will be enrolled and treated with 300-520 mg BID of AXL1717 for 28 days. The primary endpoint of the first phase is to determine the recommended Phase 2 dose (RP2D) of AXL1717 and to assess the safety and toxicity of AXL1717. The study has a 3+3 design and the first cohort will be treated with 400 mg AXL1717 BID for 28 days repeated in up to 5 cycles. The highest dose level without DLT or with maximally one DLT out of 6 patients will be the RP2D. Non-progressing patients may be treated for a total of five 28-day cycles (24 weeks).
IGF-1 receptor inhibitor
Other Name: picropodophyllin
AXL1717, as a ready-to-use suspension of picropodophyllin for oral administration, will be distributed in bottles for single use at a concentration of 25 mg/mL. Fixed doses will be used, i.e. there are no adjustments for weight or body surface. There will be no randomization or blinding in the study.
The trial will be divided in two phases. In the first phase, 10-20 patients will be enrolled and treated with 300-520 mg BID of AXL1717 for 28 days. The primary endpoint of the first phase is to determine the recommended Phase 2 dose (RP2D) of AXL1717 in patients with recurrent or progressive glioblastoma and to assess the safety and toxicity of AXL1717 in this patient population. The study has a 3+3 design and the first cohort will be treated with 400 mg AXL1717 BID for 28 days repeated in up to 5 cycles. If dose-limiting toxicity (DLT) such as neutropenia occurs, dosing will be interrupted and the individual patient will, following normalization, be restarted on the same or a lower dose level according to standardized procedure. If two or three of the first 3 patients on a specific dose level experience a DLT during the first 28 days of treatment with AXL1717, the following patients will be treated with a lower dose level. If one DLT occurs during the first 28 days of dosing in the first 3 three patients another 3 patients will be treated with the same dose level. If 2 of the 6 patients display DLT, the next patients will be treated with a lower dose level. The highest dose level without DLT or with maximally one DLT out of 6 patients will be the RPTD. All assessments with respect to dose adjustments for subsequent cohorts will be done during the first 28 days of treatment. Non-progressing patients may be treated for a total of five 28-day cycles (24 weeks).
In the second phase, 12 patients will be enrolled and treated with the identified RP2D of AXL1717 for 28 days repeated in five cycles. The primary endpoints of phase II is to assess the proportion of patients who are progression-free at 24 weeks and to assess safety, tolerability, and adverse event profile of AXL1717.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01721577
|Contact: Robert Aiken, MDemail@example.com|
|Contact: Jeanne Sixta, RNfirstname.lastname@example.org|
|United States, Illinois|
|Rush University Medical Center||Recruiting|
|Chicago, Illinois, United States, 60612|
|Contact: Jeanne Sixta, RN 312-942-2388 email@example.com|
|Principal Investigator: Robert Aiken, MD|
|Principal Investigator:||Robert Aiken, MD||Rush University Medical Center|