A Phase I Dose Escalation Study of Erlotinib in Combination With Theophylline

NCT02080078 | Terminated Phase 1

• 1 other identifier: Theophylline 1.0
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to determine the use of theophylline in patients with NSCLC and advanced solid malignancies and whether treatment with theophylline will help lower or diminish the side effect of diarrhea in patients taking erlotinib. Patients will be enrolled in one of two parts of the study to verify the lowest dose of theophylline that is effective and the highest dose of erlotinib that can be tolerated with theophylline. If this study shows that theophylline is able to inhibit erlotinib induced diarrhea, it will help demonstrate that patients using the tyrosine kinase inhibitor (TKIs), erlotinib, can use it effectively at higher doses without experiencing severe diarrhea.

Conditions

Non-small Cell Lung Cancer; Advanced Solid Malignancies

Keywords

Erlotinib; Theophylline; Diarrhea

Outcome Measures

Primary Outcomes (1)

• The lowest effective dose of theophylline that will prevent or maximally ameliorate erlotinib's diarrhea at the standard dose of erlotinib at 150 mg/day taken daily for 28 days every 28 days

  28 days

Secondary Outcomes (1)

• The highest dose of erlotinib that can be administered with theophylline and can be administered with an acceptable safety profile

  28 days

Study Arms (2)

Increasing dose of Theophylline

EXPERIMENTAL

Patients will be put on the standard dose of 150 mg/day of erlotinib. Patients will be entered into the study on different dose levels of theophylline (100 mg/bid, 150 mg/bid, 200 mg/bid, or 200 mg/tid) for 28 days to find what is the lowest dose that effectively controls the diarrhea caused by erlotinib.

Drug: Theophylline; Drug: Erlotinib

Increasing dose of erlotinib

EXPERIMENTAL

Patients will be kept on a specified dose of theophylline while the dose of erlotinib increases in each group of patients enrolled (200 mg/qd, 225 mg/qd, or 250 mg/qd) for 28 days to determine what the maximum dose of erlotinib that can be given with theophylline and maintain a safety profile.

Drug: Theophylline; Drug: Erlotinib

Interventions

Theophylline DRUG

Also known as: Theo-Dur

Increasing dose of Theophylline; Increasing dose of erlotinib

Erlotinib DRUG

Also known as: Tarceva

Increasing dose of Theophylline; Increasing dose of erlotinib

Eligibility Criteria

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

You may qualify if:

• Signed informed consent obtained before any study specific procedure. Patients must be able to understand and willing to sign the written informed consent.
• Subjects with histologically confirmed, advanced, metastatic or refractory solid malignancy who are not candidates for standard therapy or patients with advanced or recurrent NSCLC
• Male / female subject ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
• Women of childbearing potential and men must agree to use adequate contraception since signing of the informed consent form until at least 8 weeks after the last study drug administration. The investigator or a designated associate is requested to advise the subject how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) as per standard of care.
• Women of childbearing potential must have a negative urine pregnancy test performed within 7 days before start of study treatment.
• Life expectancy at least 8 weeks
• Adequate bone marrow, renal function and liver function as assessed by the following laboratory requirements conducted within 7 days of starting the study treatment:
• Platelet count ≥ 100.000/cubic millimeters (mm3), hemoglobin (Hb) ≥ 9.0 g/dl, absolute neutrophil count (ANC) ≥ 1500/mm3.
• Total bilirubin ≤ 1.5 x the upper limit of normal range (ULN). Mildly elevated total bilirubin (\<6 mg/dL) is allowed if Gilbert's syndrome is documented.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤5 x ULN for subjects whose cancer involves their liver including liver metastasis)
• Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for subjects whose cancer involves their liver including liver metastasis).
• Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min as calculated using the Cockcroft-Gault formula
• International normalized ratio (INR) ≤ 1.5 x ULN. Subjects who are being treated with heparin are allowed to participate.

You may not qualify if:

• Prior treatment with erlotinib. Patients permanently withdrawn from study participation will not be allowed to re-enter the study.
• Symptomatic metastatic brain or meningeal tumors unless the patient is \> 6 months from definitive therapy, has no evidence of tumor growth on an imaging study within 4 weeks prior to study entry and is not on dexamethasone and clinically stable with respect to the tumor at the time of study entry.
• Major surgery, open biopsy, or significant traumatic injury within 28 days before starting the study treatment
• History of organ allograft
• Non-healing wound, skin ulcer, or bone fracture
• Uncontrolled concurrent medical illness including uncontrolled hypertension defined as systolic blood pressure \>150 millimeter of mercury (mmHg) or diastolic blood pressure \>90 mmHg, despite medical management
• History of cardiac disease: congestive heart failure \> NYHA (New York Heart Association) Class II; unstable angina (symptoms of angina at rest), new-onset angina (within the last 3 months), myocardial infarction within the past 6 months prior to screening (Visit 1); cardiac ventricular arrhythmias requiring anti-arrhythmic therapy (except for beta-blockers and digoxin)
• Pleural effusion or ascites that causes respiratory compromise (NCI-CTCAE version 4.0 Grade ≥ 2 dyspnea)
• Interstitial lung disease with ongoing signs and symptoms within 28 days before starting the study treatment
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication
• Subjects with evidence or history of bleeding diathesis; any hemorrhage or bleeding event CTCAE Grade ≥ 3 or higher within 4 weeks of start of investigational treatment
• Dehydration CTCAE Grade ≥ 1
• Unresolved toxicity higher than NCI-CTCAE version 4.0 Grade 1 (excluding alopecia, anemia or lymphopenia) attributed to any prior systemic or radiation therapy or other medical or surgical procedure
• Known hypersensitivity to erlotinib, study drug class, or excipients in the formulation
• Ongoing or active infection (bacterial, fungal, or viral, e.g. human immunodeficiency virus (HIV)) of NCI-CTCAE version 4.0 Grade ≥ 2

Sponsors & Collaborators

• AHS Cancer Control Alberta: lead
• Cross Cancer Institute: collaborator

Study Sites (1)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Diarrhea

Interventions

Theophylline; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinazolines

Study Officials

• Michael Sawyer, MD

  Alberta Health services

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 12, 2014
• First Posted: March 6, 2014
• Study Start: September 1, 2014
• Primary Completion: March 30, 2019
• Study Completion: April 30, 2019
• Last Updated: May 3, 2019

Record last verified: 2019-05

Locations

CA (1)