Ifetroban in Treating Patients With Malignant Solid Tumors at High Risk of Metastatic Recurrence

PRIMARY OBJECTIVES:

I. To assess the safety and feasibility of ifetroban sodium (ifetroban) administration in
patients with malignant solid tumors at high risk of metastatic recurrence, after completion
of all planned (neo)adjuvant locoregional and systemic therapies.

SECONDARY OBJECTIVES:

I. To assess rate of metastatic recurrence after completion of ifetroban in patients with
malignant solid tumors.

EXPLORATORY OBJECTIVES:

I. To quantify pharmacodynamic markers of ifetroban effects.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP 1 (IFETROBAN): Patients receive ifetroban sodium orally (PO) once daily (QD). Courses
repeat every 28 days for 12 months in the absence of disease progression or unacceptable
toxicity.

GROUP 2 (PLACEBO): Patients receive a placebo PO QD. Courses repeat every 28 days for 12
months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then up to 12
months.

Inclusion Criteria:

- Signed and dated written informed consent.

- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.

- One of the following current diagnoses:

- Stage IIa to III triple negative breast cancer (TNBC).

- Stage I to II pancreatic adenocarcinoma.

- Lung Cancer.

- Stage IIa to III non-small cell lung cancer (NSCLC).

- Limited stage small cell lung cancer (SCLC).

- Stage IIa to III esophageal or gastroesophageal (GE) junction cancers (squamous
cell carcinoma [SCCA] or adenocarcinoma).

- Stage IIa to III stomach cancer.

- Patients must have completed all standard locoregional and systemic therapy for their
cancer.

- Administration of an investigational agent prior to enrollment needs to be completed
at least 30 days prior to enrollment.

- Patients must have recovered (=< grade 1 toxicities) from effects of local (surgery,
radiation) or systemic treatments.

- Platelet count >= 100,000 per mL of blood.

- Hemoglobin >= 9/g/dL (may have been transfused).

- Serum creatinine =< 1.5 x upper limit of normal (ULN) or estimated creatinine
clearance >= 50 mL/min as calculated using the Cockcroft-Gault (CG) equation.

- Total serum bilirubin =< 1.5 times upper limit of normal (ULN).

- Aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT/serum glutamate-pyruvate transaminase [SGPT]) =< 2.5 x
ULN.

- International normalized ratio (INR) below upper limit of normal (ULN).

- Female patients of childbearing potential and non-sterile males must agree to use at
least two methods of acceptable contraception from 15 days prior to first trial
treatment administration until at least 5 months after study participant's final dose
of study drug.

* Note: Females of childbearing potential are defined as those who are not surgically
sterile or post-menopausal (i.e. patient has not had a bilateral tubal ligation, a
bilateral oophorectomy, or a complete hysterectomy; or has not been amenorrheic for 12
months without an alternative medical cause). Post-menopausal status in females under
55 years of age should be confirmed with a serum follicle-stimulating hormone (FSH)
level within laboratory reference range for postmenopausal women. Non-sterile males
are those who have not had a vasectomy with documentation of the absence of sperm in
the ejaculate.

- Patients unable to read/write in English are eligible to participate in the overall
study but will not participate in the Patient-Reported Outcome questionnaires
throughout the trial.

- Re-enrollment of a subject that has discontinued the study as a pre-treatment screen
failure (i.e. a consented patient who did not receive study drugs) is permitted. If
reenrolled, the subject must be re-consented. Only the screening procedures performed
outside of protocol-specified timing must be repeated.

Exclusion Criteria:

- Clinical evidence of residual or distant disease after completion of standard
treatment.

- Current use of anti-platelet drugs (acetylsalicylic acid [ASA], nonsteroidal
anti-inflammatory drugs [NSAIDs], clopidogrel, argatroban, etc.) or anticoagulants
(warfarin, heparin products, etc.).

- Active malignancy within 5 years prior to current diagnosis except for in situ disease
or cancer with very high curability rate (i.e. testicular cancer, etc.).

- Uncontrolled co-morbid serious systemic illnesses that in the opinion of the
investigator could compromise therapeutic safety.

- No concurrent anticancer therapy. Required washout from prior therapy:

- Chemotherapy: 21 days.

- Major surgery: 14 days (provided wound healing is adequate).

- Radiation: 7 days.

- Investigational/Biologic Therapy: 30 days.

- Current symptomatic congestive heart failure (New York Heart Association > class II),
unstable cardiac arrhythmia requiring therapy (e.g. medication or pacemaker), unstable
angina (e.g. new, worsening or persistent chest discomfort), or uncontrolled
hypertension (systolic > 160 mmHg or diastolic > 100mmHg). Or any of the following
occurring within 6 months (180 days) prior to first dose of study drugs: Myocardial
infarction, coronary/peripheral artery bypass graft, cerebrovascular accident or
transient ischemic attack. (Use of antihypertensive medication to control blood
pressure is allowed.)

- Ongoing peptic ulcer disease requiring treatment. History of gastrointestinal bleed.
Severe gastro-esophageal reflux disease requiring treatment.

- History of bleeding diathesis.

- Planned elective major surgical intervention while taking ifetroban.

- Pregnant or breastfeeding females.

- Prisoners or subjects who are involuntarily incarcerated.

- Known psychiatric condition, social circumstance, or other medical condition
reasonably judged by the patient's study physician to unacceptably increase the risk
of study participation; or to prohibit the understanding or rendering of informed
consent or anticipated compliance with scheduled visits, treatment schedule,
laboratory tests and other study requirements.