Lung Cancer, Nonsmall CellPhase 1NCT02991651
Study of IRX4204 With Erlotinib in Previously Treated Advanced NSCLC
A Phase 1 study testing IRX4204 and erlotinib in people with Lung Cancer, Nonsmall Cell, run by Io Therapeutics at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer, Nonsmall Cell
- What is being tested?
- IRX4204 and erlotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Dec 2016to 9 May 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Geisel School of Medicine at Dartmouth
Lebanon, New Hampshire, 03756
About this study
Official title: 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;
Read more
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.
Read the detailed description
Numerous studies in pre-clinical models and in human clinical trials have clearly established the potential for the use of rexinoids in the treatment and prevention of cancer. IRX4204, a second generation rexinoid, is a highly potent and specific activator of RXRs. Because IRX4204 is significantly more potent and more selective for the RXRs relative to the RARs than a first generation approved RXR agonist drug, bexarotene, it potentially will be associated with fewer adverse events and greater activity in clinical use. Preclinical studies of the combination of IRX4204 plus erlotinib, and previous clinical studies of the combination of the bexarotene plus erlotinib indicated at least additive beneficial effects for treatment of NSCLC. This study seeks to investigate the safety and activity of IRX4204 in combination with erlotinib in patients with previously treated advanced NSCLC.
- Conditions
- Lung Cancer, Nonsmall Cell
- Being tested
- IRX4204, erlotinib
- Keywords
- RXR agonist IRX4204 erlotinib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IRX4204Drug
RXR agonist
erlotinibDrug
inhibitor of phosphorylation of the tyrosine kinase associated with the epidermal growth factor receptor
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1 | Experimental | IRX4204 5 mg/day PO + erlotinib 100 mg/day PO Receives: Drug: IRX4204; Drug: erlotinib |
| Dose Level 2 | Experimental | IRX4204 5 mg/day PO + erlotinib 150 mg/day PO Receives: Drug: IRX4204; Drug: erlotinib |
| Dose Level 3 | Experimental | IRX4204 10 mg/day PO + erlotinib 150 mg/day PO Receives: Drug: IRX4204; Drug: erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
To determine the recommended phase II dose (RP2D) for the combination of IRX4204 and erlotinib.
Measured: 30 days
Secondary outcomes (5)
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
Measured: one month
disease control rate (defined as rate of stable disease + partial response + complete response)
Measured: six months
progression free survival (PFS)
Measured: six months
overall survival (OS)
Measured: six months
response rate by RECIST 1.1
Measured: six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2016 (estimated)
- Study start7 Dec 2016
- Primary completion9 May 2025
- Study completion9 May 2025
Why it stopped: Study drug supply expired. No replacement manufactured. Sponsor did not want to continue study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung Cancer, Nonsmall CellStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Io Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Dartmouth College
- Responsible party
- Sponsor
- Investigators
- Martin E Sanders, MD, Study director, Io Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02991651
- Sponsor's protocol ID
- IRX4204 NSCLC 1 01 2015
- Status last verified
- May 2025
- First submitted
- 7 Dec 2016
- Last updated
- 14 May 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of IRX4204 in Combination With Erlotinib in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT02991651
- Acronym / sponsor ID
- IRX4204 NSCLC 1 01 2015
- Conditions
- Lung Cancer, Nonsmall Cell
- Keywords
- RXR agonist IRX4204 erlotinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study drug supply expired. No replacement manufactured. Sponsor did not want to continue study.
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Io TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Dartmouth College
- Study start
- 7 Dec 2016 (actual)
- Primary completion
- 9 May 2025 (actual)
- Study completion
- 9 May 2025 (actual)
- First posted
- 13 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Numerous studies in pre-clinical models and in human clinical trials have clearly established the potential for the use of rexinoids in the treatment and prevention of cancer. IRX4204, a second generation rexinoid, is a highly potent and specific activator of RXRs. Because IRX4204 is significantly more potent and more selective for the RXRs relative to the RARs than a first generation approved RXR agonist drug, bexarotene, it potentially will be associated with fewer adverse events and greater activity in clinical use. Preclinical studies of the combination of IRX4204 plus erlotinib, and previous clinical studies of the combination of the bexarotene plus erlotinib indicated at least additive beneficial effects for treatment of NSCLC. This study seeks to investigate the safety and activity of IRX4204 in combination with erlotinib in patients with previously treated advanced NSCLC.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1 | Experimental | Drug: IRX4204, Drug: erlotinibIRX4204 5 mg/day PO + erlotinib 100 mg/day PO |
| Dose Level 2 | Experimental | Drug: IRX4204, Drug: erlotinibIRX4204 5 mg/day PO + erlotinib 150 mg/day PO |
| Dose Level 3 | Experimental | Drug: IRX4204, Drug: erlotinibIRX4204 10 mg/day PO + erlotinib 150 mg/day PO |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IRX4204RXR agonist | Drug | Dose Level 1, Dose Level 2, Dose Level 3 |
| erlotinibinhibitor of phosphorylation of the tyrosine kinase associated with the epidermal growth factor receptor | Drug | Dose Level 1, Dose Level 2, Dose Level 3 |
Primary outcome
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.
5 secondary outcomes
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
disease control rate (defined as rate of stable disease + partial response + complete response)
Time frame: six months
progression free survival (PFS)
Time frame: six months
overall survival (OS)
Time frame: six months
response rate by RECIST 1.1
Time frame: six months
Results and safety
The study was stopped early (reason given: Study drug supply expired. No replacement manufactured. Sponsor did not want to continue study.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin E Sanders, MD study director
Io Therapeutics, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IRX4204 and erlotinib in people with Lung Cancer, Nonsmall Cell, run by Io Therapeutics at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study drug supply expired. No replacement manufactured. Sponsor did not want to continue study.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2025.