Study of IRX4204 With Erlotinib in Previously Treated Advanced NSCLC
| Status: | Recruiting |
|---|---|
| Conditions: | Lung Cancer, Lung Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 8/9/2018 |
| Start Date: | May 2016 |
| End Date: | December 2019 |
| Contact: | Martin E Sanders, MD |
| Email: | msanders@io-therapeutics.com |
| Phone: | (650) 219-5973 |
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.
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.
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.
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.
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.
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