- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02991651
Study of IRX4204 With Erlotinib in Previously Treated Advanced NSCLC
A Phase I Study of IRX4204 in Combination With Erlotinib in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer
Patient selection: a) Pathological confirmation of non-small cell lung cancer without activating EGFR mutations; b) Advanced stage disease (IV or IIIB with malignant effusion) with at least two prior chemotherapy regimens; c) No available curative therapy; d) Pregnant women are excluded; e) Informed consent.
Pretreatment evaluation: a) Medical history and physical examination; b) Hepatic and renal function (bilirubin, aspartate aminotransaminase, creatinine); c) Preoperative staging evaluation including CT-chest or PET/CT scan;
Treatment plan: Three dose levels of IRX4204 and erlotinib will be studied using intra-patient dose escalation for dose levels 1 and 2. These study agents will be administered orally until progression of disease, unacceptable toxicities, activation of a phase II study of the combination, or exhaustion of the IRX4204 drug supply.
Evaluation on study: Adverse events will be graded on a scale of 0 to 5, using the Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0. Efficacy will be assessed using the RECIST v1.1 criteria based on CT-chest or PET/CT scan after 8 weeks of study treatment.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
New Hampshire
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Lebanon, New Hampshire, United States, 03756
- Geisel School of Medicine at Dartmouth
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed stage IV non-small cell lung cancer, or recurrent non-small cell lung cancer which is not amenable to curative intent therapy.
- Documented disease progression on at least two prior lines of chemotherapy for advanced NSCLC. Progression within 6 months of adjuvant chemotherapy or definitive chemoradiation will count as one line of therapy.
- Age ≥18 years.
- ECOG performance status ≤2.
- Ability to take pills by mouth.
- Patients must have normal organ and marrow function as defined below:
- Leukocytes ≥3,000/mcL
- Absolute neutrophil count ≥1,500/mcL
- Platelets ≥100,000/mcL
- Hemoglobin ≥8.5 g/dL
- Total bilirubin ≤1.5 x institutional upper limit of normal (ULN)
- AST(SGOT)/ALT(SGPT) ≤2.5 × ULN or ≤5 x ULN if metastases to the liver
- Creatinine clearance ≥40 mL/min
- Patients with asymptomatic brain metastases are allowed, as long as they are stable and do not require treatment with anticonvulsants or escalating doses of steroids. Maximum daily dose of steroids should be prednisone 20 mg or equivalent. Radiation therapy for brain metastases must be completed at least 14 days prior to treatment on protocol.
- Women of child-bearing potential and men must agree to use highly effective contraception (if using hormonal birth control must add a second barrier method; abstinence) prior to study entry, for the duration of study participation as well as for at least 1 month after the last dose of IRX4204. Men treated or enrolled on this protocol must also agree to use highly effective contraception prior to the study, for the duration of study participation and 3 months after completion of IRX4204 administration.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study.
- Activating EGFR mutations detected in the tumor.
- Prior treatment with an EGFR tyrosine kinase inhibitor.
- Prior treatment with IRX4204 or another retinoid or rexinoid administered for the purpose of cancer treatment. Prior topical retinoid use is allowed.
- History of allergic reactions attributed to IRX4204 or erlotinib or to compounds of similar chemical or biologic composition.
- 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.
- Pregnant and nursing women.
- Patients with a history of another active malignancy within the past two years, with the exception of non-melanoma cutaneous malignancy, cervical carcinoma in situ, or ductal carcinoma in situ which has been successfully treated with curative intent therapy.
- Any gastrointestinal disorder expected to limit absorption of IRX4204 or erlotinib.
- Patients with a history of active thyroid disease. However, patients with a history of hypothyroidism maintained in euthyroid state by supplementation with thyroid hormone, or a thyroid hormone containing preparation may be enrolled.
- Patients taking coumarin-derived anticoagulants.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dose Level 1
IRX4204 5 mg/day PO + erlotinib 100 mg/day PO
|
RXR agonist
inhibitor of phosphorylation of the tyrosine kinase associated with the epidermal growth factor receptor
|
Experimental: Dose Level 2
IRX4204 5 mg/day PO + erlotinib 150 mg/day PO
|
RXR agonist
inhibitor of phosphorylation of the tyrosine kinase associated with the epidermal growth factor receptor
|
Experimental: Dose Level 3
IRX4204 10 mg/day PO + erlotinib 150 mg/day PO
|
RXR agonist
inhibitor of phosphorylation of the tyrosine kinase associated with the epidermal growth factor receptor
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety of co-administration of IRX4204 + erlotinib to determine recommended phase 2 dose based on number of participants experiencing treatment-related adverse events as assessed as grade 4 by CTCAE v4.0
Time Frame: 30 days
|
To determine the recommended phase II dose (RP2D) for the combination of IRX4204 and erlotinib.
|
30 days
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
toxicity profile of the combination of IRX4204 and erlotinib based on number of participants experiencing treatment-related grades 1-4 adverse events as assessed by CTCAE v4.0
Time Frame: one month
|
one month
|
disease control rate (defined as rate of stable disease + partial response + complete response)
Time Frame: six months
|
six months
|
progression free survival (PFS)
Time Frame: six months
|
six months
|
overall survival (OS)
Time Frame: six months
|
six months
|
response rate by RECIST 1.1
Time Frame: six months
|
six months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Martin E Sanders, MD, Io Therapeutics, Inc.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Erlotinib Hydrochloride
Other Study ID Numbers
- IRX4204 NSCLC 1 01 2015
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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