NCT01824901

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jan 2014

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 2, 2013

Completed
3 days until next milestone

First Posted

Study publicly available on registry

April 5, 2013

Completed
10 months until next milestone

Study Start

First participant enrolled

January 15, 2014

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 9, 2014

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2015

Completed
11 months until next milestone

Results Posted

Study results publicly available

March 1, 2016

Completed
Last Updated

June 29, 2023

Status Verified

June 1, 2023

Enrollment Period

6 months

First QC Date

April 2, 2013

Results QC Date

December 15, 2015

Last Update Submit

June 14, 2023

Conditions

Recurrent Non-small Cell Lung CancerSquamous Cell Lung Cancer

Keywords

AZD4547recurrent non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

  • Maximum Tolerated Dose (MTD) of FGFR Inhibitor AZD4547

    A total of 3 dose levels of AZD4547 were planned: 40mg (level 1), 60mg (level 2), and 80mg (level 3) in combination with a standard dose of docetaxel (75mg/m\^2). The starting dose level of AZD4547 was 40 mg. This portion of the study used a standard 3+3 design with patients enrolled in cohorts of 3. The plan was to recommend the maximum tolerated dose (MTD) as the dose level to be used in the phase II portion of the study. MTD is defined as the highest dose level at which less than or equal to 1 of 6 subjects experience dose limiting toxicity (DLT).

    Assessed during cycle 1 (21 days)

Study Arms (4)

Phase I

EXPERIMENTAL

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.

Drug: docetaxelDrug: AZD4547

Arm I (docetaxel; phase II step I)

EXPERIMENTAL

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.

Drug: docetaxel

Arm II (docetaxel and AZD4547; phase II step I)

EXPERIMENTAL

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.

Drug: docetaxelDrug: AZD4547

Phase II step II

EXPERIMENTAL

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.

Drug: AZD4547

Interventions

docetaxelDRUG

Given IV

Also known as: Taxotere, NSC 628503
Arm I (docetaxel; phase II step I)Arm II (docetaxel and AZD4547; phase II step I)Phase I
AZD4547DRUG

Given PO

Also known as: NSC 765338
Arm II (docetaxel and AZD4547; phase II step I)Phase IPhase II step II

Eligibility Criteria

Age25 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
  • Women of childbearing potential and sexually active males must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Measurable or non-measureable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; baseline measurements and evaluations of all sites of disease must be obtained =\< 4 weeks prior to registration
  • Histologically or pathologically confirmed squamous NSCLC; patients whose tumors contain mixed NSCLC histologies are eligible if squamous morphology is predominant; mixed tumors with small cell anaplastic elements are not eligible
  • Life expectancy \>= 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
  • Adequate organ and marrow function
  • Mean resting corrected QT interval (QTc) \< 470 msec obtained from 3 consecutive electrocardiograms

You may not qualify if:

  • Pregnant or breast-feeding women
  • Clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) e.g. complete left bundle branch block, third degree heart block
  • Factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval
  • Prior treatment with docetaxel (except in the adjuvant setting), or AZD4547
  • Prior treatment with any other chemotherapy, immunotherapy or anticancer agents within 2 weeks prior to registration
  • Current evidence or previous history of retinal pigmented epithelium detachment (RPED)
  • Previous laser treatment or intra-ocular injection for treatment of macular degeneration
  • Current evidence or previous history of dry or wet age-related macular degeneration
  • Current evidence or previous history of retinal vein occlusion (RVO)
  • Current evidence or previous history of retinal degenerative diseases (e.g. hereditary)
  • Current evidence or previous history of any other clinically relevant chorioretinal defect
  • Uncontrolled brain metastases
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD4547, docetaxel or other agents used in the study
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the investigational drug, previous significant bowel resection, or any other significant gastrointestinal disorder that could, in the opinion of the Investigator, interfere with the absorption of AZD4547
  • +14 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287-8936, United States

Location

Eastern Cooperative Oncology Group (ECOG) Research Base

Brookline, Massachusetts, 02445-7648, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

DocetaxelAZD4547

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenes

Results Point of Contact

Title
Study Statistician
Organization
ECOG-ACRIN Statistical Office
617-632-3012

Study Officials

  • Charles Rudin

    Eastern Cooperative Oncology Group

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 2, 2013

First Posted

April 5, 2013

Study Start

January 15, 2014

Primary Completion

July 9, 2014

Study Completion

April 1, 2015

Last Updated

June 29, 2023

Results First Posted

March 1, 2016

Record last verified: 2023-06

Data Sharing

IPD Sharing
Will not share

Locations

US(5)