Dasatinib and Erlotinib in Non-Small Cell Lung Cancer (NSCLC)

NCT00826449 | Completed Phase 1 Results

• 2 other identifiers: 2008-0353NCI-2012-01653
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of the Phase I portion of this study is to find the highest tolerable dose of the combination of dasatinib and erlotinib hydrochloride that can be given to patients with advanced solid tumors. The goal of the Phase II portion of this study is to learn if this combination is effective when given to patients with non-small cell lung cancer. The safety of this combination will be studied in both phases.

Conditions

Lung Cancer; Non-Small Cell Lung Cancer

Keywords

Advanced Solid Tumors; Advanced Cancer; Non-Small Cell Lung Cancer; NSCLC; Solid Tumor Malignancy; Dasatinib; BMS-354825; Sprycel®; Erlotinib; Erlotinib hydrochloride; Tarceva; OSI-774

Outcome Measures

Primary Outcomes (1)

• Phase I: Maximum Tolerable Dose (MTD) of Dasatinib Given With Erlotinib Hydrochloride

  MTD defined as the highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). Dose-limiting toxicity (DLT) defined using NCI Common Terminology Common Terminology Criteria for Adverse Events (CTCAE) version 3 as: grade 3 or higher non-hematologic toxicity (excluding initial nausea and vomiting), grade 4 neutropenia, febrile neutropenia, or grade 4 thrombocytopenia. Grade 3-4 nausea and vomiting that cannot be controlled within 2 weeks with anti-emetics considered a DLT.

  Baseline and at Day 21

Secondary Outcomes (2)

• Phase II: Number of Participant With Response According to Response Evaluation Criteria in Solid Tumors (RECIST)

  12 Weeks

• Phase II: Progression-Free Survival (PFS) Rate

  12 Weeks

Study Arms (1)

Phase I

EXPERIMENTAL

Dasatinib + Erlotinib

Drug: Dasatinib; Drug: Erlotinib

Interventions

Dasatinib DRUG

Starting dose of 70 mg by mouth daily for 21 day cycle.

Also known as: BMS-354825, Sprycel®

Phase I

Erlotinib DRUG

150 mg by mouth daily every 21 day cycle.

Also known as: Erlotinib hydrochloride, Tarceva, OSI-774

Phase I

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Advanced malignancy that is appropriate for systemic therapy without curative intent.
• Patients must provide verbal and written informed consent indicating they are aware of the investigational nature of the study. Parental consent and patient assent is required for those aged 16-17.
• Patients must be at least 16 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Adequate hematologic, hepatic, and renal function as follows: creatinine \< 1.5 x the institutional upper limit of normal (ULN), total bilirubin \< 2.0 x ULN, AST and ALT \< 2.5 x ULN, absolute granulocytes \>/= 1500/mm\^3; platelets \>/= 75,000 mm\^3; hemoglobin \>/= 10 g/dL.
• Serum potassium, magnesium, and phosphate within the institutional limits of normal. Patients with low potassium, phosphate, or magnesium levels may be repleted to allow for protocol entry.
• Serum calcium \>/= the institutional limits of normal. Patients with low calcium levels may be repleted to allow for protocol entry.
• Ability to take oral medication (dasatinib and erlotinib must be swallowed whole)
• Patients-both males \& females-w/reproductive potential must agree to use an adequate method of contraception to include hormonal contraceptives (birth control pills, injections, implants), intrauterine device (IUD), barrier contraceptive with spermicide, and/or abstinence throughout the study \& for at least 4 wks after the study drugs are stopped. Females w/ reproductive or childbearing potential include any female who has experienced menarche \& who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal
• Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 72 hours prior to the start of study drug administration.
• Asymptomatic brain metastases with prior cranial irradiation or resection are acceptable if there is no bleeding, no midline shift, and no need for steroids or anti-convulsants. Asymptomatic brain metastasis without prior treatment are acceptable if the largest lesion is less than 7 mm in diameter, there is no bleeding, midline shift, nor need for steroids or anti-convulsants.
• Patient agrees to discontinue St. Johns Wort at least 5 days before starting dasatinib or erlotinib.
• Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia.
• The patient's O\^2 saturation must be \>92% on room air.
• (Phase II only) - Patient has never received prior therapy with dasatinib, or erlotinib, or another epidermal growth factor receptor (EGFR) or Src family kinase (SFK) inhibitor.

You may not qualify if:

• Women who are pregnant, breastfeeding, or have child-bearing potential and are unwilling/unable to use an acceptable method of contraception for the entire study period and for at least 4 weeks after cessation of the study drugs. All women of child-bearing potential must have a negative pregnancy test prior to first receiving protocol therapy. If the pregnancy test is positive, the patient must not receive dasatinib or erlotinib, and must not be enrolled on the study
• Radiotherapy to ribs, sternum, pelvis, vertebrae or skull within 4 weeks prior to entering the study. (If none of these axial skeletal areas are included in the radiotherapy field, patients may have received palliative radiotherapy to long bones provided that it has ended at least 2 weeks prior to initiation of dasatinib-erlotinib therapy.)
• Patients with any of the following cardiac problems should be excluded: (a) Uncontrolled angina, congestive heart failure, or myocardial infarction within the previous 6 months; (b) Diagnosed congenital long QT syndrome; (c) Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); (d) Prolonged \[1\] corrected QT interval (QTc) interval on pre-entry electrocardiogram (\> 450 msec in women or \>440 msec in men). If the automated reading is prolonged, the ECG should be manually over read.
• Patients with pericardial effusion \> grade 1 (by Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0).
• Patients with pleural effusion \> grade 2 (by CTCAE v3.0). A grade 3 pleural effusion that is managed by a thoracentesis or an indwelling catheter is allowable as long as supplemental oxygen is not required.
• Patients with any condition that impairs their ability to swallow, retain, or absorb dasatinib or erlotinib tablets are excluded. This includes any condition resulting in an inability to take oral medication, a requirement for IV alimentation, prior surgical procedures that have resulted in chronic malabsorption, or active peptic ulcer disease.
• Patients with \> grade 2 neuropathy
• Patients with a history of pulmonary fibrosis (other than in a radiated field).
• Patients with inflammatory bowel disease or uncontrolled chronic diarrhea.
• Patients with a history of significant bleeding disorder unrelated to cancer, including: (a) Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease); (b) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies); (c) Ongoing or recent (\</= 3 months) significant gastrointestinal bleeding, defined as clinically evident hematemesis or hematochezia requiring therapeutic intervention.
• Known HIV-positive patients are ineligible because of the potential for pharmacokinetic interactions between dasatinib and antiretroviral therapy. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• Pts currently receiving any of the following medications will be excluded: (a) Any concurrent systemic anticancer therapy; (b) Any concurrent investigational agents (c) Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Pts must discontinue such drugs 7 days or more prior to starting dasatinib):i. quinidine, procainamide, disopyramide;ii. amiodarone, sotalol, ibutilide, dofetilide;iii. erythromycin, clarithromycin;iv. chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
• The patient has received prior investigational therapy, chemotherapy, radiotherapy, or major surgery within 3 weeks of initiating study drug.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bristol-Myers Squibb: collaborator
• OSI Pharmaceuticals: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Gold KA, Lee JJ, Harun N, Tang X, Price J, Kawedia JD, Tran HT, Erasmus JJ, Blumenschein GR, William WN, Wistuba II, Johnson FM. A phase I/II study combining erlotinib and dasatinib for non-small cell lung cancer. Oncologist. 2014 Oct;19(10):1040-1. doi: 10.1634/theoncologist.2014-0228. Epub 2014 Aug 28.

  PMID: 25170013 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Dasatinib; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Faye Johnson, Associate Professor, Thoracic/Head & Neck Med Oncology
• Organization: University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

Study Officials

• Faye M. Johnson, MD, PhD, BS

  UT MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2009
• First Posted: January 22, 2009
• Study Start: February 1, 2009
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: June 28, 2016
• Results First Posted: October 21, 2015

Record last verified: 2016-05

Locations

US (1)