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A Phase I Dose Escalation Study of Erlotinib in Combination With Theophylline | Clinical Trials | Clareo Health

TERMINATEDPHASE1

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

A Phase I, Single-center, Non-randomized, Open-label Study to Determine the Lowest Effective Theophylline Dose That Decreased Erlotinib's Diarrhea at the Standard Dose of 150 mg/Day and to Determine the Highest Erlotinib Dose in Combination With Theophylline That Can be Administered to Patients

NCT02080078•AHS Cancer Control Alberta

View on ClinicalTrials.gov

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.

Detailed Description

Erlotinib is a tyrosine kinase inhibitor (TKI), which is a newer, effective treatment for cancer patients. TKIs are the only class of anticancer drugs that are predominately used as single agents. TKIs were hoped to lack side effects but can cause severe enough diarrhea that patients frequently stop treatment, even if TKIs are controlling their cancer. TKIs inhibit nucleoside transporters (NTs), perturbing regulation of adenosine levels in the intestine. It is possible that the reason for the inability to use TKIs in combination therapies has been their additive effects on NTs causing unacceptable diarrhea. It has been shown that TKIs are potent NT inhibitors, therefore it will theoretically inhibit NTs of intestinal epithelial cells causing an accumulation of extracellular adenosine resulting in chloride secretory diarrhea. If this hypothesis is correct, it has profound implications for oncology, since diarrhea is one of the dose-limiting toxicities of TKIs. It has been shown that co-incubating cells with 8-phenyltheophylline (8PT), which is an A2B adenosine receptor antagonist, block chloride secretion caused by nitrobenzyl-mercaptopurine ribonucleoside (NBMPR). Theophylline is also a methylxanthine and is a commercially available and licensed example of a 8PT. As it is already known that erlotinib is effective, it is used as a control factor in the first arm of the study and will be increased in the second arm to see what the maximally tolerated dose is when in combination with a controlled dose of theophylline.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•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.
+4 more criteria

Exclusion Criteria

•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
+13 more criteria

Locations (1)

Cross Cancer Institute

Edmonton, Alberta, Canada

Key Dates

Start Date

September 1, 2014

Primary Completion Date

March 30, 2019

Completion Date

April 30, 2019

Last Updated

May 3, 2019

Enrollment

ACTUAL participants

Conditions

Non-small Cell Lung CancerAdvanced Solid Malignancies

Interventions

Theophylline

DRUG

Erlotinib

DRUG

Sacituzumab Tirumotecan (MK-2870) Versus Pemetrexed and Carboplatin Combination Therapy in Participants With Epidermal Growth Factor (EGFR)-Mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors (MK-2870-009)

NCT06305754

Non-small Cell Lung Cancer (NSCLC)

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RECRUITINGPHASE3

A Clinical Study of Calderasib (MK-1084) and Other Treatments for Participants With Non-Small Cell Lung Cancer (MK-1084-007/KANDLELIT-007)

NCT07190248

Non-small Cell Lung Cancer

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: May 3, 2019Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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

Inclusion Criteria

Exclusion Criteria

Sacituzumab Tirumotecan (MK-2870) Versus Pemetrexed and Carboplatin Combination Therapy in Participants With Epidermal Growth Factor (EGFR)-Mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors (MK-2870-009)

A Clinical Study of Calderasib (MK-1084) and Other Treatments for Participants With Non-Small Cell Lung Cancer (MK-1084-007/KANDLELIT-007)

Study of Izalontamab Brengitecan (BMS-986507) Versus Platinum-Pemetrexed for EGFR-mutated Non-small Cell Lung Cancer After Failure of EGFR TKI Therapy (IZABRIGHT-Lung01)

Beamion LUNG-3: A Study to Test Whether Zongertinib Helps People With Surgically Removed, Non-small Cell Lung Cancer With HER2 Mutations Compared With Standard Treatment

Phase III, Open-label, Study of First-line Dato-DXd in Combination With Rilvegostomig for Advanced Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations

Reduced CT + Anti-PD-1 as First Line Tx in Vulnerable Older Adults w/Adv <50% PD-L1 Non-Small Cell Lung Cancer (NSCLC)