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Trial record 12 of 636 for:    Louisville AND Dayton

Lung-MAP: AZD4547 as Second-Line Therapy in Treating FGFR Positive Patients With Recurrent Stage IV Squamous Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT02965378
Recruitment Status : Active, not recruiting
First Posted : November 16, 2016
Last Update Posted : January 4, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

Brief Summary:
This phase II/III trial studies how well FGFR inhibitor AZD4547 (AZD4547) works in treating patients with stage IV squamous cell lung cancer that has come back after previous treatment. This is a sub-study that includes all screened patients positive for the fibroblast growth factor receptor (FGFR) biomarker. FGFR can cause tumor cells to grow more quickly. AZD4547 may decrease the activity of FGFR and may be able to shrink tumors.

Condition or disease Intervention/treatment Phase
FGFR1 Gene Amplification FGFR1 Gene Mutation FGFR2 Gene Amplification FGFR2 Gene Mutation FGFR3 Gene Amplification FGFR3 Gene Mutation Recurrent Squamous Cell Lung Carcinoma Stage IV Squamous Cell Lung Carcinoma AJCC v7 Drug: Docetaxel Drug: FGFR Inhibitor AZD4547 Other: Laboratory Biomarker Analysis Phase 2 Phase 3

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate if there is sufficient evidence to continue to the Phase III component by evaluating the objective response rate (ORR) with AZD4547 in FGFR-positive patients. (Phase II) II. If the study meets the criteria specified in S1400, the study will be amended to include a follow-on randomized Phase III trial. (Phase III)

SECONDARY OBJECTIVES:

I. To evaluate investigator-assessed progression free survival (IA-PFS) and overall survival (OS) in FGFR-positive patients treated with AZD4547. (Phase II) II. To evaluate the duration of response (DoR) among FGFR positive patients treated with AZD4547 who achieve a complete response (CR) or partial response (PR) (confirmed and unconfirmed) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. (Phase II) III. To evaluate the frequency and severity of toxicities associated with AZD4547 in FGFR positive patients. (Phase II)

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To identify additional predictive tumor/blood biomarkers that may modify response or define resistance to the AZD4547 beyond the chosen biomarker for biomarker-driven sub-studies.

II. To identify potential resistance biomarkers at disease progression. III. To establish a tissue/ blood repository from patients with refractory squamous cell carcinoma (SCCA) of the lung.

OUTLINE: As of 12/18/2015, patients are assigned to Arm I.

ARM I: Patients receive FGFR inhibitor AZD4547 orally (PO) twice daily (BID) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II (CLOSED TO ACCRUAL 12/18/2015): Patients receive docetaxel intravenously (IV) on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, patients may be eligible to re-register to Arm III.

ARM III: Patients in Arm II eligible for re-registration receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, all patients are followed up every 6 months for the first 2 years and then at the end of the year 3 from date of sub-study/re-registration.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of AZD4547 for Previously Treated FGFR-Positive Patients With Stage IV Squamous Cell Lung Cancer (Lung-Map Sub-Study)
Actual Study Start Date : June 16, 2014
Estimated Primary Completion Date : April 1, 2022
Estimated Study Completion Date : April 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Docetaxel

Arm Intervention/treatment
Experimental: Arm I (AZD4547)
Patients receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: FGFR Inhibitor AZD4547
Given PO
Other Name: AZD4547

Other: Laboratory Biomarker Analysis
Correlative studies

Experimental: Arm II (docetaxel - closed to accrual 12/18/2015)
Patients receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, patients may be eligible to re-register to Arm III.
Drug: Docetaxel
Given IV
Other Names:
  • Docecad
  • RP56976
  • Taxotere
  • Taxotere Injection Concentrate

Other: Laboratory Biomarker Analysis
Correlative studies

Experimental: Arm III (AZD4547 re-registration)
Patients in Arm II eligible for re-registration receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: FGFR Inhibitor AZD4547
Given PO
Other Name: AZD4547

Other: Laboratory Biomarker Analysis
Correlative studies




Primary Outcome Measures :
  1. Objective Response Rate (confirmed and unconfirmed, complete and partial) (Design #2, Phase II) [ Time Frame: Up to 3 years ]
    The investigational therapy arm will be judged to have provided sufficient evidence to proceed to the Phase III component if the objective response rate is at least 25%. Response rates and associated confidence intervals will be calculated.


Secondary Outcome Measures :
  1. Duration of response among patients who achieve a complete response or partial response by Response Evaluation Criteria in Solid Tumors 1.1 (Design #2, Phase II) [ Time Frame: Up to 3 years ]
    Estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median duration of response.

  2. Overall survival with investigational therapy (Design #2, Phase II) [ Time Frame: Up to 3 years ]
    A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival comparing the two treatment arms at the levels specified. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.

  3. Progression free survival with investigational therapy (Design #2, Phase II) [ Time Frame: Up to 3 years ]
    A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to progression free survival comparing the two treatment arms at the levels specified. A Cox proportional hazards (PH) model will be used to estimate the hazard ratios and associated confidence intervals.

  4. Severity of toxicities associated with investigational therapy (Design #2, Phase II) [ Time Frame: Up to 3 years ]
    Analysis of toxicities will be performed using a chi-square or Fisher?s exact test, as appropriate.


Other Outcome Measures:
  1. Screen success rate [ Time Frame: Up to 3 years ]
    Will be monitored by the percentage of screened patients that register to a therapeutic sub-study.

  2. Treatment arm randomization acceptance rate [ Time Frame: Up to 3 years ]
    Will be monitored by the percentage of patients that receive at least one dose of the treatment they are randomized to receive.



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMON ELIGIBILITY CRITERIA as specified in S1400: Phase II/III Biomarker-Driven Master Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map)
  • Patients must be assigned to S1400D
  • Patients must not be taking, nor plan to take while on protocol treatment and for 14 days after the last dose of study treatment, drugs, herbal supplements or foods that are known to be strong/moderate CYP3A4 or CYP2D6 inhibitors and/or inducers
  • Patients must not have received nitrosourea or mitomycin C within 42 days prior to sub-study registration
  • Patients must not have had any prior exposure to any agent with FGFR inhibition as its primary pharmacology
  • Patients must not have a mean resting corrected QT interval (QTc) > 450 msec obtained from 3 consecutive electrocardiograms (ECGs); performed within 28 days prior to sub-study registration; patients must not have any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block); patients must not have any 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
  • Patients must not be planning to receive any concomitant medication known to prolong QT interval
  • Patients must be able to take oral medications; patient may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of AZD4547 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
  • Patients must not have a history of hypersensitivity to active or inactive excipients of AZD4547 or drugs with a similar chemical structure or class to AZD4547
  • Patients must not have any of the following ophthalmological criteria: 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); or current evidence or previous history of any other clinically relevant chorioretinal defect
  • Patients must have an eye exam performed within 28 days prior to sub-study registration; patients with uncontrolled glaucoma or intra-ocular pressure >= 21 mm Hg at screening should be referred for ophthalmological management and the condition controlled prior to registration
  • Patients must have albumin, urinalysis, and Troponin I obtained within 7 days prior to sub-study registration
  • Patients must have corrected calcium and phosphate < upper limit or normal (ULN) obtained within 7 days prior to sub-study registration
  • Patients must have multigated acquisition (MUGA)/echocardiogram performed within 28 days prior to sub-study registration
  • Patients must also be offered participation in banking for future use of specimens
  • STEP 2 TO AZD4547 RE-REGISTRATION:
  • Patients must have progressed on Arm 2 (docetaxel) of this sub-study
  • Patients must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 21 days prior to re-registration; patients must have recovered (=< grade 1) from any side effects of prior therapy
  • Patients must have measurable disease documented by computed tomography (CT) or magnetic resonance imaging (MRI); the CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality; measurable disease must be assessed within 28 days prior to re-registration; pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease; non-measurable disease must be assessed within 42 days prior to re-registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form; patients whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to registration
  • Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to Step 2 Re-registration; patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment prior to re-registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to re-registration
  • Patients must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment; concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable
  • Patients must have albumin, urinalysis, and Troponin I obtained within 7 days prior to substudy registration
  • Patients must have corrected calcium and phosphate < ULN obtained within 7 days prior to sub-study registration
  • Patients must have MUGA/echocardiogram performed within 28 days prior to sub-study registration
  • Patients must not have any of the following ophthalmological criteria: 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); or current evidence or previous history of any other clinically relevant chorioretinal defect; patients must have an eye exam performed within 28 days prior to Step 2 re-registration; patients with uncontrolled glaucoma or intra-ocular pressure >= 21 mm Hg at screening should be referred for ophthalmological management and the condition controlled prior to crossover registration
  • Patients must not be taking, nor plan to take while on protocol treatment and for 14 days after the last dose of study treatment, drugs, herbal supplements or foods that are known to be strong/moderate CYP3A4 or CYP2D6 substrates
  • Patients must not have a mean resting corrected QT interval (QTc) > 450 msec obtained from 3 consecutive electrocardiograms (ECGs); performed within 28 days prior to Step 2 re-registration; patients must not have any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block); patients must not have any 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
  • Absolute neutrophil count (ANC) >= 1,500/mcl obtained within 28 days prior to Step 2 re-registration
  • Platelet count >= 100,000 mcl obtained within 28 days prior to Step 2 re-registration
  • Hemoglobin >= 9 g/dL obtained within 28 days prior to Step 2 re-registration
  • Serum bilirubin =< institutional upper limit of normal (IULN); for patients with liver metastases, bilirubin must be =< 5 x IULN within 28 days prior to Step 2 re-registration
  • Either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 2 x IULN within 28 days prior to Step 2 re-registration (if both ALT and AST are done, both must be =< 2 IULN); for patients with liver metastases, either ALT or AST must be =< 5 x IULN (if both ALT and AST are done, both must be =< 5 x IULN)
  • Patients must have a serum creatinine =< the IULN OR measured or calculated creatinine clearance >= 50 mL/min using the Cockroft-Gault formula
  • Patients must have Zubrod performance status of 0-1 documented within 28 days prior to Step 2 re-registration
  • Patients must not have any grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, and myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia
  • Patients must not have documented evidence of acute hepatitis or have an active or uncontrolled infection
  • Patients with a known history of human immunodeficiency virus (HIV) seropositivity: 1. Must have undetectable viral load using standard HIV assays in clinical practice; 2. Must have cluster of differentiation (CD)4 count >= 400/mcL; 3. Must not require prophylaxis for any opportunistic infections (i.e., fungal, mycobacterium avium complex [mAC], or pneumocystis pneumonia [PCP] prophylaxis); 4. Must not be newly diagnosed within 12 months prior to re-registration
  • Prestudy history and physical exam must be obtained within 28 days prior to re-registration
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
  • Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
  • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
  • Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)
  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02965378


  Show 1084 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Vassiliki Papadimitrakopoulou Southwest Oncology Group

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Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT02965378     History of Changes
Other Study ID Numbers: S1400D
NCI-2014-01381 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S1400D
S1400D ( Other Identifier: SWOG )
S1400D ( Other Identifier: CTEP )
U10CA180888 ( U.S. NIH Grant/Contract )
First Posted: November 16, 2016    Key Record Dates
Last Update Posted: January 4, 2019
Last Verified: January 2019

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Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Carcinoma
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action