Phase I Erlotinib and Dovitinib (TKI258) in Advanced Non-small Cell Lung Cancer (NSCLC)

This study has suspended participant recruitment.
(Interim analysis of PK and toxicity data)
Sponsor:
Collaborators:
Genentech
Novartis
Information provided by (Responsible Party):
Heather Wakelee, Stanford University
ClinicalTrials.gov Identifier:
NCT01515969
First received: December 16, 2011
Last updated: February 1, 2013
Last verified: February 2013
  Purpose

This phase I trial studies the side effects and best dose of giving erlotinib and dovitinib together to treat patients with metastatic non-small cell lung cancer. Erlotinib blocks the epidermal growth factor receptor (EGFR) and has known activity in non-small cell lung cancer and dovitinib blocks the fibroblast growth factor receptor (FGFR) and other targets which may be important to treat lung cancer. The combination of both drugs may work better than either drug alone, but may also have increased side effects. This trial will look at the side effects of combining the drugs and look for how effective the combination may be.


Condition Intervention Phase
Recurrent Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Drug: erlotinib hydrochloride
Drug: dovitinib lactate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Erlotinib and Dovitinib (TKI258) in Advanced Non-small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Measure toxicity to determine the MTD of the combination of erlotinib hydrochloride and dovitinib lactate [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Dose limiting toxicity (DLT) is defined as a CTCAE v4.0 toxicity >= grade 3 or 4 occurring after 3 weeks of treatment. If 2 of 6 patients experience a DLT, then the MTD will be defined as the dose tolerated by the cohort preceding the cohort experiencing the DLT.


Secondary Outcome Measures:
  • ORR (complete response [CR]+ partial response [PR]) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • PFS [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • OS [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: July 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (enzyme inhibitor therapy)
Patients receive erlotinib hydrochloride PO QD. Starting on day 15, patients also receive dovitinib lactate PO QD on days 1-5 of each week. Treatment continues in the absence of disease progression or unacceptable toxicity.
Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Drug: dovitinib lactate
Given PO
Other Names:
  • CHIR-258
  • receptor tyrosine kinase inhibitor TKI258
  • RTK inhibitor TKI258
  • TKI258

Detailed Description:

PRIMARY OBJECTIVES:

I. To characterize the safety and tolerability of the combination of erlotinib (erlotinib hydrochloride) and dovitinib (dovitinib lactate), assessing for toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

II. To determine the maximum tolerated dose (MTD) of the combination of erlotinib and dovitinib.

SECONDARY OBJECTIVES:

I. To evaluate overall response rate (ORR), progression free survival (PFS), and overall survival (OS) of patients receiving the combination of erlotinib and dovitinib, although this phase will allow for patients who received any number of prior treatments, including prior treatment with erlotinib.

II. To evaluate the potential impact of dovitinib on erlotinib pharmacokinetics (PK).

OUTLINE: This is a dose-escalation study.

Patients receive erlotinib hydrochloride orally (PO) once daily (QD). Starting on day 15, patients also receive dovitinib lactate PO QD on days 1-5 of each week. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 12 months.

  Eligibility

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

Inclusion Criteria:

  • Histologically-confirmed metastatic non-small cell lung cancer
  • One or more primary or metastatic lesions measurable in at least one dimension by modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria (v1.1) within 4 weeks prior to entry of study
  • Patients who have failed any number of prior therapies, including those previously treated with erlotinib
  • Life expectancy > 2 months
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (>= 1500/mm^3)
  • Platelets (PLT) >= 100,000/mm^3
  • Hemoglobin (Hgb) >= 9 g/dL
  • Serum creatinine =< 1.5 x upper limit of normal (ULN)
  • Serum bilirubin =< 1.5 x ULN (regardless of whether liver metastases are present at baseline)
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) =< 3.0 x ULN (regardless of whether liver metastases are present at baseline)
  • Ability to understand and the willingness to provide verbal and written informed consent
  • Patients - both males and females- with reproductive potential (i.e. menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures throughout the study; women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration

Exclusion Criteria:

  • Patients who have received the last administration of chemotherapy or immunotherapy =< the timeframe defined below after the end of the cycle of the last treatment, prior to starting study drug, or who have not recovered from the side effects of such therapy:

    • Patients who have received the last administration of chemotherapy/immunotherapy in a daily schedule =< 7 days prior to starting study drug
    • Patients who have received the last administration of chemotherapy/immunotherapy in a weekly schedule =< 2 weeks prior to starting study drug
    • Patients who have received the last administration of chemotherapy/immunotherapy in a 2-weekly schedule =< 3 weeks prior to starting study drug
    • Patients who have received the last administration of chemotherapy/immunotherapy in a 3-weekly schedule =< 4 weeks prior to starting study drug
    • Patients who have received the last administration of chemotherapy/immunotherapy in a 4-weekly schedule =< 5 weeks prior to starting study drug
    • Patients who have received the last administration of nitrosourea, mitomycin-C =< 6 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
  • Patients who have received wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) =< 4 weeks or limited field radiation for palliation =< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Patients who have undergone major surgery =< 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • If history of other primary cancer, subject will be eligible only if she or he has:

    • Curatively resected non-melanomatous skin cancer, basal cell carcinoma, squamous cell carcinoma
    • Curatively treated cervical carcinoma in situ
    • Other primary solid tumor curatively treated with no known active disease present and no treatment administered for the last 3 years
  • Subjects known to have chronic or active hepatitis B or C infection with impaired hepatic function (ineligible if AST and ALT > 2.5 x ULN)
  • History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with study participation or study drug administration or may interfere with the conduct of the study or interpretation of study results
  • Patients who continue to smoke (given that smoking decreases serum levels of erlotinib)
  • Female subject who is breast-feeding or who has positive serum pregnancy test 72 hours prior to enrollment
  • Any of the following concurrent severe and/or uncontrolled medical conditions within 6 months of enrollment which could compromise participation in the study:

    • Unstable angina pectoris
    • Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without anti-hypertensive medication; initiation or adjustment of antihypertensive medication(s) is allowed prior to study entry
    • Left ventricular ejection fraction (LVEF) assessed by 2-D echocardiogram (ECHO) < 50% or lower limit of normal (whichever is higher) or multiple gated acquisition scan (MUGA) < 45% or lower limit of normal (whichever is higher)
    • Myocardial infarction
    • Serious uncontrolled ventricular arrhythmia
    • Clinically significant resting bradycardia
    • Uncontrolled diabetes
    • Transient Ischemic Attach (TIA)
    • Cerebrovascular accident (CVA)
    • Pulmonary embolism (PE)
    • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
    • Serious active or uncontrolled infection
    • Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
    • Chronic renal disease
    • Cirrhosis, chronic active hepatitis or chronic persistent hepatitis
  • Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin or enoxaparin
  • Women of child-bearing potential, who are biologically able to conceive, not employing two forms of highly effective contraception; highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes during the study and must be continued for 8 weeks after the end of study treatment; oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study; women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (e.g., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test =< 14 days prior to starting study treatment
  • Patients unwilling to or unable to comply with the protocol
  • There may be danger of harm to study participants because of human immunodeficiency virus (HIV) comorbidity or drug interactions
  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: NCT01515969

Locations
United States, California
Stanford University
Stanford, California, United States, 94305
Sponsors and Collaborators
Heather Wakelee
Genentech
Novartis
Investigators
Principal Investigator: Heather Wakelee Stanford University
  More Information

No publications provided

Responsible Party: Heather Wakelee, Assistant Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT01515969     History of Changes
Other Study ID Numbers: LUN0044, NCI-2011-03333, SU-08012011-8166, 21659
Study First Received: December 16, 2011
Last Updated: February 1, 2013
Health Authority: United States: Institutional Review Board
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
Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014