NCT02134886

Terminated

Phase 1

A Phase I/Pharmacokinetic Study of Erlotinib for Advanced Non-small Cell Lung Cancer in Persons With HIV Infection

National Cancer Institute (NCI)5 sites in 1 country48 target enrollmentJuly 2014

ConditionsHIV Infection Recurrent Non-Small Cell Lung Carcinoma Stage IIIA Non-Small Cell Lung Cancer Stage IIIB Non-Small Cell Lung Cancer Stage IV Non-Small Cell Lung Cancer

InterventionsErlotinib Hydrochloride Laboratory Biomarker Analysis Pharmacological Study Quality-of-Life Assessment

DrugsErlotinib Hydrochloride

Overview

Phase: Phase 1
Intervention: Erlotinib Hydrochloride
Conditions: HIV Infection
Sponsor: National Cancer Institute (NCI)
Enrollment: 48
Locations: 5
Primary Endpoint: Incidence of toxicities evaluated with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (v4.0)
Status: Terminated
Last Updated: 10 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This phase I trial studies the side effects and best dose of erlotinib hydrochloride in treating non-small cell lung cancer that has spread to other parts of the body or cannot be removed by surgery in patients with human immunodeficiency virus (HIV) infection. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Erlotinib hydrochloride is a standard drug used for treating lung cancer, however, it is not yet known whether it is safe to give erlotinib hydrochloride to patients who also have HIV infection or not.

Detailed Description

PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of erlotinib (erlotinib hydrochloride) as a single agent in non-small cell lung cancer participants with HIV infection and to determine the maximum tolerated dose of erlotinib in combination with antiretroviral therapy in this participant population. SECONDARY OBJECTIVES: I. To evaluate the efficacy of erlotinib in advanced non-small cell lung cancer persons with HIV infection. II. To investigate possible pharmacokinetic interactions between erlotinib and antiretroviral therapy in persons with HIV infection, while accounting for nicotine exposure. III. To investigate the effects of therapy on participant immune status and HIV viral load. IV. To preliminarily evaluate known molecular and phenotypic correlates of improved clinical outcomes associated with epidermal growth factor receptor (EGFR) inhibitors. OUTLINE: This is a dose-escalation study. Patients receive erlotinib hydrochloride orally (PO) once daily (QD) 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 for 30 days.

Registry

clinicaltrials.gov

Start Date

July 2014

End Date

September 2015

Last Updated

10 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

National Cancer Institute (NCI)

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Participants must have known HIV infection and histologically confirmed non-small cell lung cancer that is metastatic or unresectable; patients will be eligible regardless of tumor EGFR mutation status
•Participants may have received any number of prior lines of chemotherapy (other than erlotinib or other EGFR-targeted therapy) for incurable non-small cell lung cancer; (first line platinum-doublet based chemotherapy plus switch maintenance chemotherapy counts as one line of therapy; prior adjuvant chemotherapy for early stage disease does not count as one line of therapy if 12 months or greater elapsed between completion of adjuvant therapy and initiation of first-line systemic therapy; if less than 12 months elapsed, adjuvant chemotherapy counts as one line of therapy)
•PARTICIPANTS WITH NO PRIOR THERAPY FOR INCURABLE LUNG CANCER: trial eligibility will be restricted to those participants whose tumors harbor known EGFR activating mutations
•PARTICIPANTS WITH PRIOR LINES OF THERAPY: all other participants (those whose tumors harbor wild-type EGFR or unknown EGFR status, or those with EGFR mutations not previously treated with erlotinib/EGFR-targeted therapy)
•At least 4 weeks must have elapsed since prior chemotherapy or biological therapy, 6 weeks if the regimen included carmustine (BCNU) or mitomycin C; prior radiation therapy to the thoracic cavity, abdomen, or pelvis must be completed at least 3 months prior to registration; radiotherapy to any other site (including bone or brain metastases) must be completed at least 28 days prior to registration
•Molecular characterization of non-squamous non-small cell lung cancer will be recommended prior to enrollment per standard of care/institutional guidelines; consistent with current National Comprehensive Cancer Network (NCCN) guidelines and the recent Food and Drug Administration (FDA)-approval indication of erlotinib for first-line treatment of advanced non-small cell lung cancer in persons with tumor EGFR mutations, participants who have known EGFR sensitizing mutations in tumors will be permitted to enter the study and receive erlotinib as initial monotherapy; for participants who have received one or more prior lines of chemotherapy, molecular characterization of tumors is required whenever possible with an understanding that inability to obtain sufficient tissue specimen for characterization will not preclude enrollment into the study
•Participants must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria; baseline measurements and evaluation of ALL sites of disease must be obtained within 4 weeks prior to registration
•Serologic documentation of HIV infection at any time prior to study entry, as evidenced by positive enzyme-linked immunosorbent assay (ELISA), positive Western blot, or any other federally approved licensed HIV test; alternatively, this documentation may include a record that another physician has documented that the participant has HIV infection based on prior ELISA and Western blot, or other approved diagnostic tests
•Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
•Life expectancy of greater than 12 weeks

Exclusion Criteria

•Participants who received prior treatment with erlotinib or other EGFR-targeted agents
•Participants who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
•Participants who are receiving any other investigational agents
•The participant has active brain metastases or epidural disease; participants with stable brain metastases previously treated with whole brain radiation or radiosurgery or participants with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 4 weeks before starting study treatment are eligible; neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment; baseline brain imaging with contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) scans for participants with known brain metastases is required to confirm eligibility
•History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib
•The participant has prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test \>= 1.3 the laboratory ULN within 7 days before the first dose of study treatment
•Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
•Participants with history of chronic diarrhea, grade \>= 2 prior to study participation; persons with up to grade 1 diarrhea will be eligible
•The participant requires chronic concomitant treatment with the following strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers OTHER than antiretroviral agents: dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, primidone, modafinil, and other enzyme inducing anti-convulsant drugs (EIACD), and St. John's Wort; use of efavirenz or etravirine is permitted for participants considered for the CYP3A4-inducer based antiretroviral therapy (ART) regimen arm (Stratum B) of the trial
•Although study participants will be eligible regardless of smoking history, smokers should be strongly advised to stop smoking while on erlotinib; smoking induces cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) enzymes and alters erlotinib exposure by 64%

Arms & Interventions

Treatment (erlotinib hydrochloride)

Patients receive erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Intervention: Erlotinib Hydrochloride

Treatment (erlotinib hydrochloride)

Patients receive erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Intervention: Laboratory Biomarker Analysis

Treatment (erlotinib hydrochloride)

Patients receive erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Intervention: Pharmacological Study

Treatment (erlotinib hydrochloride)

Patients receive erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Intervention: Quality-of-Life Assessment

Outcomes

Primary Outcomes

Incidence of toxicities evaluated with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (v4.0)

Time Frame: Up to 30 days

Maximum tolerated dose of erlotinib hydrochloride defined as the dose level in which less than or equal to 1 out of 6 participants experiences dose-limiting toxicity evaluated with NCI CTCAE v4.0

Time Frame: 28 days

Secondary Outcomes

Response assessed via RECIST 1.1(Up to 30 days)
CD4+ counts(Up to 30 days)
CD8+ counts(Up to 30 days)
HIV viral load(Up to 30 days)
Pharmacokinetic parameters of erlotinib hydrochloride, including half-life (T1/2), clearance (Cl), and area under the curve (AUC)(Pre-treatment, 1, 2, 3, 4, 6, 8, and 24 hours post treatment)
Incidence of erlotinib hydrochloride-associated skin rash(Up to 30 days)