Dose Escalation Study of I-131-CLR1404 in Subjects With Cancer That Does Not Respond to Treatment or Has Returned

Inclusion criteria

• Relapsed or refractory advanced solid malignancy or choice not to pursue standard treatment. Tumor types allowed: non-small cell lung, triple negative breast, soft tissue sarcoma, colorectal, gastric, esophageal, prostate, ovarian cancer
• ≥ 1 lesion that qualifies as a "target lesion" based on RECIST 1.1
• Ambulatory w/ECOG performance status 0 to 2 and estimated life expectancy ≥ 4 mo.
• 18 years or older
• Judged by Investigator to have initiative and means to be compliant with protocol and w/n geographical proximity to make required study visits
• Ability to read, understand and provide written informed consent for initiation of any study related procedures (subject or legal representative)
• Brain metastasis acceptable if clinical condition stable ≥ 1 mo. Subjects with brain metastasis requiring steroids must have been on a stable or tapering dose of corticosteroids ≥ 1 mo. prior to enrollment
• Negative serum pregnancy test w/n 24 hours of enrollment (Female subjects of childbearing potential)
• Agreement to use effective contraception method (oral contraceptives, double-barrier methods, intrauterine device, Norplant, Depo-Provera) during study and 90 days following last dose

Exclusion criteria

• Subject or physician plans concomitant chemotherapy, therapeutic radiation and/or biological treatment for cancer including immunotherapy while on study. Localized palliative radiation therapy for bone pain allowed if clinically indicated. Ongoing hormonal therapy may be continued
• Received > 3 previous cytotoxic chemotherapy regimens
• Received > 25% of total bone marrow irradiated, total body or hemi-body irradiation or prior radioisotope therapy (except for benign thyroid disease)
• Diffuse lung disease or interstitial spread of carcinoma
• Prior radiation therapy or chemotherapy w/n 4 weeks of study start
• Extradural tumor in contact with spinal cord or tumor located where swelling in response to therapy may impinge upon spinal cord
• Other active medical condition or organ disease that may compromise safety or interfere with safety and/or outcome evaluation of study drug
• Laboratory abnormalities, including but not limited to: WBC < 3000/uL, Absolute neutrophil count < 1500/uL, Platelets < 150,000/uL, Hemoglobin ≤ 9.0 gm/dL, Total bilirubin > 1.5 x upper limit of normal for age, SGOT or SGPT > 3 x upper limit of normal for age if no liver metastases or > 5 x upper limit of normal for age in the presence of liver metastases, Serum creatinine > 1.5 x upper limit of normal for age, INR ≥ 2.0, 2+ proteinuria or casts indicative of intrinsic renal disease
• Treatment with investigational drug, investigational biologic, or investigational therapeutic device w/n 28 days of initiating study treatment
• Received severely marrow toxic drugs (eg nitrosoureas, mitomycin)
• Received blood transfusions or hematopoietic growth factor therapy w/n 30 days of study start
• Received prior stem cell transplantation
• Clinically significant cardiac co-morbidities including congestive heart failure (New York Heart Association class III-IV heart disease), left ventricular ejection fraction < 40%, unstable angina pectoris, serious cardiac arrhythmia requiring medication or pacemaker, myocardial infarction within past 6 months
• Concurrent or recent (w/n 1 month) use of thrombolytic agents or full-dose anticoagulants (except to maintain patency of preexisting, permanent indwelling IV catheters). Therapy with low-molecular weight heparin is acceptable as long as INR < 2.0
• Uncontrolled hypertension as defined by systolic blood pressure > 150 mm/Hg, diastolic blood pressure > 100 mm/Hg or uncontrolled diabetes that would compromise subject safety or interfere with safety and/or outcome evaluation of study drug
• Grade II-IV peripheral vascular disease or peripheral vascular surgery w/n past year
• Major surgery w/n 4 wks. of enrollment
• Poor venous access and unable to receive study drug into a peripheral venous catheter
• Significant traumatic injury w/n past 4 wks.
• Ongoing or active infection requiring antibiotics or with fever >38.1º C (>101º F) w/n 3 days of first scheduled day of dosing
• Receiving concurrent hemodialysis or peritoneal dialysis
• Known positive for HIV, Hepatitis C (active, previously treated or both) or is Hepatitis B core antigen positive
• Pregnant or lactating
• Hospitalized