Nintedanib in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Failed Up to Two Previous Chemotherapy Regimens

Stage IV Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01948141
• Other study ID #: I 225512
• Secondary ID: NCI-2013-01618I
• Status: Active, not recruiting
• Phase: Phase 2
• First received: September 18, 2013
• Last updated: June 8, 2016
• Start date: January 2014

Study information

• Verified date: June 2016
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 6
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Recurrent Non-small Cell Lung Cancer
• Squamous Cell Lung Cancer
• Stage III Non-small Cell Lung Cancer
• Stage IV Non-small Cell Lung Cancer

Intervention

Drug:
• nintedanib
Given PO

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University Hospitals Case Medical Center	Cleveland	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute	Boehringer Ingelheim, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS rate within the entire FGFRI amplified group defined as the proportion of patients who are alive and progression-free	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.	At 6 months	No
Secondary	PFS rate for the entire FGFR1 amplified group vs. the FGFRI wild-type patients	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.	Time from study entry to the first of either disease progression or death, assessed at 6 months	No
Secondary	PFS rate between each of the FGFR1 amplified groups (low, intermediate, and high) vs. the FGFR1 wild-type patients	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.	Time from study entry to the first of either disease progression or death, assessed at 6 months	No
Secondary	PFS rate for each of the FGFRI amplified groups (low, intermediate, high) in comparison to historical controls	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.	Time from study entry to the first of either disease progression or death, assessed at 6 months	No
Secondary	OS	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.	From study entry to death from any cause, assessed up to 3 years	No
Secondary	Tumor response defined as complete response (CR) or partial response by RECIST 1.1 criteria		Up to 3 years	No
Secondary	Incidence of adverse events (AEs) accessed by the National Cancer Institute (NCI) CTCAE version 4.0	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.	Up to 30 days post-treatment	Yes