Conditions: Recurrent Non-small Cell Lung Cancer Squamous Cell Lung Cancer
Keywords: AZD4547 recurrent non-small cell lung cancer
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 2
Healthy volunteers: no

Brief summary:
This randomized phase I/II trial studies the side effects and best dose of fibroblast growth factor receptor (FGFR) inhibitor AZD4547 when given with docetaxel and to see how well it works in treating patients with recurrent non-small cell lung cancer. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. FGFR inhibitor AZD4547 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether docetaxel and FGFR inhibitor AZD4547 are more effective when given together or separately.

Detailed description:
PRIMARY OBJECTIVES:

I. Determination of a recommended phase II dose for the combination of docetaxel and AZD4547 (FGFR inhibitor AZD4547). (Phase I) II. Estimation and comparison of progression-free survival (PFS) of each treatment arm. (Phase II)

SECONDARY OBJECTIVES:

I. Pharmacokinetic evaluation of docetaxel with or without concomitant AZD4547. Pharmacokinetic evaluation of AZD4547 with concomitant docetaxel. (Phase I) II. Safety assessment and toxicity characterization of the combination. (Phase I) III. Initial assessment of clinical activity of the combination. (Phase I) IV. Response rate. (Phase II) V. Overall survival. (Phase II) VI. Estimation of response to single agent AZD4547 among patients who crossover from single agent docetaxel. (Phase II) VII. Further safety assessment and toxicity characterization of AZD4547 alone and in combination with docetaxel. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of FGFR inhibitor AZD4547 followed by a randomized phase II study.

PHASE I:

Patients receive docetaxel intravenously (IV) over 60 minutes on day 1 and FGFR inhibitor AZD4547 orally (PO) twice daily (BID) on days 2-15 of course 1 and days 1-14 of all subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

PHASE II, STEP I: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive docetaxel IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who experience progressive disease may then receive FGFR inhibitor AZD4547 PO BID on days 1-14.

ARM II: Patients receive docetaxel IV as in Arm I and FGFR inhibitor AZD4547 PO BID on days 1-14.

In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

PHASE II, STEP II:

Patients receive FGFR inhibitor AZD4547 PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 years.

This study opened to accrual on September 19, 2013 and was suspended to accrual on January 29, 2014 after each of the first two patients had been registered to the first dose level of the phase I and experienced dose limiting toxicities (DLTs) during week 1 of cycle 1. The study was subsequently terminated on April 17, 2014 after having met the predefined criteria for closure per the phase I study design.

Arms:
arm 1: Patients receive docetaxel IV over 60 minutes on day 1 and FGFR inhibitor AZD4547 PO BID on days 2-15 of course 1 and days 1-14 of all subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. arm 2: Patients receive docetaxel IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who experience progressive disease may then register to step II treatment and receive FGFR inhibitor AZD4547 PO BID on days 1-14. arm 3: Patients receive docetaxel IV over 60 minutes on day 1 and FGFR inhibitor AZD4547 PO BID on days 1-14. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. arm 4: Patients receive FGFR inhibitor AZD4547 PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Interventions: intervention 1: docetaxel intervention 2: AZD4547
Intervention descriptions: intervention 1: Given IV intervention 2: Given PO

Protocol document: