Trial record 1 of 1 for:    NCT01948141
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Nintedanib in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Failed Up to Two Previous Chemotherapy Regimens

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Roswell Park Cancer Institute
Sponsor:
Collaborators:
Boehringer Ingelheim
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01948141
First received: September 18, 2013
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

This phase II trial studies how well nintedanib works in treating patients with advanced non-small cell lung cancer who have failed up to two previous chemotherapy regimens. Nintedanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Recurrent Non-small Cell Lung Cancer
Squamous Cell Lung Cancer
Stage III Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Drug: nintedanib
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: FGFR1 Amplification as A Predictor of Efficacy in A Biomarker-Driven Phase II Study of BIBF 1120 in Advanced Squamous Cell Lung Cancer Patients Who Have Failed Up to Two Prior Chemotherapeutic Regimens

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • PFS rate within the entire FGFRI amplified group defined as the proportion of patients who are alive and progression-free [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
    Tested at the 1-sided 0.10 significance level with all eligible, treated patients. Distributions of PFS will be estimated using the Kaplan-Meier method.


Secondary Outcome Measures:
  • PFS rate for the entire FGFR1 amplified group vs. the FGFRI wild-type patients [ Time Frame: Time from study entry to the first of either disease progression or death, assessed at 6 months ] [ Designated as safety issue: No ]
    Distributions of PFS will be estimated using the Kaplan-Meier method. Any comparisons between FGFRI groups will be done via the log-rank test for OS, along with the chi-square (or Fisher's exact test) for categorical data like tumor response and adverse events.

  • PFS rate between each of the FGFR1 amplified groups (low, intermediate, and high) vs. the FGFR1 wild-type patients [ Time Frame: Time from study entry to the first of either disease progression or death, assessed at 6 months ] [ Designated as safety issue: No ]
    Distributions of PFS will be estimated using the Kaplan-Meier method. Any comparisons between FGFRI groups will be done via the log-rank test for OS, along with the chi-square (or Fisher's exact test) for categorical data like tumor response and adverse events.

  • PFS rate for each of the FGFRI amplified groups (low, intermediate, high) in comparison to historical controls [ Time Frame: Time from study entry to the first of either disease progression or death, assessed at 6 months ] [ Designated as safety issue: No ]
    Distributions of PFS will be estimated using the Kaplan-Meier method. Any comparisons between FGFRI groups will be done via the log-rank test for OS, along with the chi-square (or Fisher's exact test) for categorical data like tumor response and adverse events.

  • OS [ Time Frame: From study entry to death from any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
    Distributions of OS will be estimated using the Kaplan-Meier method. Any comparisons between FGFRI groups will be done via the log-rank test for OS, along with the chi-square (or Fisher's exact test) for categorical data like tumor response and adverse events.

  • Tumor response defined as complete response (CR) or partial response by RECIST 1.1 criteria [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Incidence of adverse events (AEs) accessed by the National Cancer Institute (NCI) CTCAE version 4.0 [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]
    Frequency tables will be reviewed to determine AE and toxicity patterns by FGFR1 groups. The frequency of AEs will be tabulated by grade across all dose levels and courses.


Estimated Enrollment: 67
Study Start Date: January 2014
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (nintedanib)
Patients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: nintedanib
Given PO
Other Names:
  • BIBF 1120
  • multitargeted tyrosine kinase inhibitor BIBF 1120
  • Tyrosine Kinase Inhibitor BIBF 1120
  • Vargatef
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the 6-month progression-free survival (PFS) rate of fibroblast growth factor receptor 1 (FGFRI) amplified squamous cell lung cancer patients treated with BIBF 1120 (nintedanib).

SECONDARY OBJECTIVES:

I. Compare the 6-month PFS rate for the entire FGFRI amplified group versus the FGFRI wild-type patients.

II. Compare the 6-month PFS rate for each FGFRI amplified group (low, intermediate, and high) versus historical controls and FGFRI wild-type patients.

III. To assess the following endpoints overall and by FGFRI group: PFS, overall survival (OS), confirmed tumor response rate, and adverse events.

TERTIARY OBJECTIVES:

I. The relation of FGFRI gene copy number with PFS, OS, confirmed response rate, and adverse events.

II. The relationship fibroblast growth factor receptor (FGFR) polymorphisms with toxicity and efficacy.

OUTLINE:

Patients receive nintedanib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 8 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with advanced histologically proven squamous cell carcinoma of the lung
  • Patients who have failed at least 1 systemic chemotherapy regimen for metastatic disease, but not more than 2 regimens
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
  • The pathologic tissue is available to determine FGFR1 amplification status
  • Presence of either evaluable disease or measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Hemoglobin (HgB) >= 9 g/dL
  • Platelets >= 100,000/uL
  • Total bilirubin =< upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 1.5 x ULN (ALT and AST =< 2.5 x ULN is acceptable if there is liver metastasis)
  • Calculated or measured creatinine clearance >= 45 mL/min
  • Patients of child-bearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment and have a negative serum or urine pregnancy test done =< 7 days prior to registration (for women of childbearing potential only)
  • Life expectancy >= 12 weeks
  • Willingness to provide the blood specimens as required by the protocol; please note that the willingness to participate pertains only to the patient and does not factor in the institution's ability to participate in any part of the translational component

Exclusion Criteria:

  • Patients with any known endothelial growth factor receptor (EGFR) mutation and/or anaplastic lymphoma receptor tyrosine kinase (ALK) translocation
  • Symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases or seizure disorder; patients with asymptomatic CNS metastases treated with whole brain radiation (WBRT) or gamma knife radiosurgery (GKR) may be enrolled >= 1 week after completion of WBRT/GKR provided toxicities are =< Common Toxicity Criteria (CTC) grade I at the time of registration and/or controlled with dexamethasone 2 mg once daily for at least 5 days at the time of study treatment; patients with symptomatic CNS metastases treated with WBRT/GKR may be enrolled >= 2 weeks after completion of WBRT/GKR provided toxicities are =< CTC grade 1 at the time of registration and neurologic symptoms controlled with dexamethasone =< 2 mg once daily for at least 1 week at the time of study treatment
  • Patients receiving palliative radiation to skeletal metastases may be registered as early as 1 week after completion of radiation therapy provided toxicities are =< CTC grade I at the time of registration
  • Any of the following prior therapies for malignancy:

    • Systemic chemotherapy =< 4 weeks prior to registration
    • Radiation therapy =< 4 weeks prior to registration (exceptions noted in the prior bullet); the site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease
    • Major surgery (i.e., laparotomy), open biopsy, or significant traumatic injury =< 4 weeks prior to registration; minor surgery =< 2 weeks prior to registration; insertion of a vascular access device is not considered major or minor surgery in this regard
    • Other investigational agent =< 30 days prior to study treatment
  • The following patients will be excluded from this study:

    • Pregnant women
    • Breastfeeding women
    • Men or women who are sexually active and unwilling to use a medically acceptable method of contraception (e.g., such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during the trial and for at least three months after end of active therapy; a highly effective method of birth control is defined as one which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly; patients will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation/salpingectomy, or post-menopausal for at least 2 years
  • Second primary malignancy with the following exceptions which are allowed:

    • Carcinoma in situ of the cervix
    • Non-melanoma skin cancer
    • History of low-grade (Gleason score =< 6) localized prostate cancer even if diagnosed < 5 years prior to registration
    • Treated stage I breast cancer even if diagnosed =< 5 years prior to registration
    • Other prior malignancy (including melanoma) allowed if it was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of BIBF 1120 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or extensive small bowel resection)
  • Leptomeningeal disease
  • Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded because of possible pharmacokinetic interactions with oral investigational agents
  • Unwilling to, or unable to, comply with the protocol
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring systemic antimicrobial therapy (including history of active or chronic hepatitis C and/or hepatitis B infection), significant pulmonary symptoms at baseline due to disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Centrally located tumors with radiographic evidence (computed tomography [CT] or magnetic resonance imaging [MRI]) of local invasion of major blood vessels
  • Significant weight loss (> 10% of baseline body mass) within past 6 months prior to inclusion into the study
  • Coagulation parameters: International normalized ratio (INR) > 2, prothrombin time (PT) and partial thromboplastin time (PTT) > 50% of deviation of institutional ULN
  • Proteinuria by Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater
  • Known inherited predisposition to bleeding or thrombosis
  • Therapeutic anticoagulation (except for low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous device) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid < 325 mg per day)
  • Baseline hemoptysis, per clinician/investigator evaluation
  • Active alcohol or drug abuse
  • History of arterial or venous thrombotic/embolic events =< 12 months prior to registration
  • Prior history with BIBF 1120 or any other vascular endothelial growth factor (VEGF)/VEGF receptor (R) inhibitor
  • New York Heart Association (NYHA) class III or IV; NOTE: patients classified as NYHA class II controlled with treatment may participate, with increased monitoring
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01948141

Locations
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Roswell Park    877-275-7724    ASKRPCI@roswellpark.org   
Principal Investigator: Alex A. Adjei         
Sponsors and Collaborators
Roswell Park Cancer Institute
Boehringer Ingelheim
Investigators
Principal Investigator: Alex Adjei Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT01948141     History of Changes
Other Study ID Numbers: I 225512, NCI-2013-01618, I 225512, P30CA016056
Study First Received: September 18, 2013
Last Updated: January 31, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 26, 2014