Date: 2013-01-21
Type of information:
phase: 1-2
Announcement: initiation of the study
Company: Axelar (Sweden)
Product: AXL1717 (picropodophyllin)
Action
mechanism: AXL1717 - picropodophyllin is a targeted oral small-molecule insulin-like growth factor 1 (IGF-1) receptor pathway inhibitor with no observable effect on the closely related insulin receptor. Most tumor cells are dependent on the IGF-1 receptor signal pathway and the IGF-1 receptor is therefore regarded as a promising target for cancer therapy. To date, there are no IGF-1 receptor inhibitor drugs on the market. Axelar is currently running a randomized Phase II clinical trial with AXL1717 in non-small cell lung cancer patients. A first-in-man Phase I/II clinical trial with AXL1717 including 49 patients has been completed demonstrating a good tolerability profile of the compound, in addition to its superior preclinical efficacy against numerous tumors.
Disease: anaplastic astrocytoma
glioblastoma
gliosarcoma
anaplastic oligodendroglioma
anaplastic oligoastrocytoma
anaplastic ependymoma
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: 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. (NCT01721577).
Latest
news: * On January 21, 2013, Axelar, a Karolinska Development AB portfolio company, has announced that an investigator sponsored Phase I/II study with AXL1717 in patients with malignant astrocytomas, a type of brain tumor, has commenced in the United States. The study is conducted at the Rush University Medical Center in Chicago in patients with relapsed or progressive malignant astrocytomas (glioblastoma and anaplastic astrocytoma), with AXL1717 - an oral small-molecule insulin-like Growth Factor 1 (IGF-1) receptor inhibitor - as the investigational drug. This study is also supported by Voices Against Brain Cancer and Gateway for Cancer Research.
