Clinical Trial: A Phase 1/2 Study of the Oral ALK/EGFR Inhibitor AP26113

Study Status: Enrolling by invitation
Recruit Status: Unknown status
Study Type: Interventional

Official Title: A Phase 1/2 Study of the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-Tumor Activity of the Oral ALK/EGFR Inhibitor AP26113

Brief Summary: The purpose of this study is 2-fold: initially, in the dose escalation phase, the goal is to determine the safety profile of orally administered AP26113, including: the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), recommended phase 2 dose (RP2D), and pharmacokinetic (PK) profile. Then, once the RP2D is established, an expansion phase will assess the preliminary anti-tumor activity of AP26113, both in non-small cell lung cancer (NSCLC) with ALK gene rearrangement (including patients with active brain metastases)or mutated EGFR, and in other cancers with abnormal targets against which AP26113 is active. Approximately 135 to 175 patients will be enrolled.

Detailed Summary: This is the first assessment of AP26113 in patients. The trial will be conducted in 2 parts: an initial dose escalation phase in 30 to 70 patients with advanced malignancies (all histologies other than leukemia), resistant to available therapies or for whom no standard or available curative treatments exist, followed by an expansion phase in 5 histologically and molecularly defined cohorts of patients (approximately 20-25 patients per cohort, approximately 105 patients altogether). The objectives of the dose escalation phase are to determine the safety, tolerability, pharmacokinetic profile, and recommended phase 2 dose (RP2D) of orally administered AP26113. The objectives of the expansion phase are to describe the preliminary anti-tumor activity (overall response rate) of AP26113 in patients with non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) gene rearrangement or mutated epidermal growth factor receptor (EGFR), and in patients with any cancers with abnormalities in ALK or other targets against which AP26113 is active, and to continue to assess safety and tolerability.
Sponsor: Ariad Pharmaceuticals

Current Primary Outcome:

  • Recommended Phase 2 Dose (RP2D) [ Time Frame: Day 1 to 28 (Cycle 1) ]
  • Overall response rate [ Time Frame: Up to 24 months after first dose ]


Original Primary Outcome:

  • Recommended Phase 2 Dose (RP2D) [ Time Frame: Day 1 to 28 (Cycle 1) ]
  • Response rate [ Time Frame: Up to 24 months after first dose ]


Current Secondary Outcome:

  • Maximum tolerated dose (MTD) [ Time Frame: Day 1 to 28 (Cycle 1) ]
  • Adverse Events as a measure of Safety and Tolerability [ Time Frame: Up to 24 months after first dose ]
  • Profile of Single Dose and Steady State Pharmacokinetics [ Time Frame: Day 1: pre-dose, 0.5, 1, 2, 4, 6, 8, and 24 hours after the first dose; pre-dose on days 8, 15 and 22; Day 29: pre-dose, 0 .5, 1, 2, 4, 6, 8, 24, 48 hours after first dose, and Cycle 3, Day 1 pre-dose sample ]
    Cmax, Tmax, AUC, half-life


Original Secondary Outcome:

  • Maximum tolerated dose (MTD) [ Time Frame: Day 1 to 28 (Cycle 1) ]
  • Adverse Events as a measure of Safety and Tolerability [ Time Frame: Up to 24 months after first dose ]
  • Profile of Single Dose and Steady State Pharmacokinetics [ Time Frame: Day 1: pre-dose, 0.5, 1, 2, 4, 6, 8, and 24 hours after the first dose; pre-dose on days 8, 15 and 22; Day 29: pre-dose, 0 .5, 1, 2, 4, 6, 8, 24, and 48 hours after first dose ]
    Cmax, Tmax, AUC, half-life


Information By: Ariad Pharmaceuticals

Dates:
Date Received: September 30, 2011
Date Started: September 2011
Date Completion: September 2015
Last Updated: August 21, 2014
Last Verified: August 2014