A Phase I/II Trial of Crolibulin (EPC2407) Plus Cisplatin in Adults With Solid Tumors With a Focus on Anaplastic Thyroid Cancer (ATC)

• INCLUSION CRITERIA:

Pathologic confirmation of cancer by the Laboratory of Pathology, National Cancer Institute (NCI)

Phase I: Diagnosis of recurrent, metastatic or primary unresectable solid tumor that does not have curative standard treatment.

Phase II: Diagnosis of recurrent, metastatic or primary unresectable anaplastic thyroid cancer (ATC), including ATC as part of a thyroid carcinoma of another histologic subtype.

Measurable disease at presentation with disease measurable by Response Evaluation Criteria in Solid Tumors (RECIST) required in the phase II cohort.

A life expectance of at least 3 months as evidenced by Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

Age greater than or equal to 18 years

Last dose of chemotherapy or experimental therapy more than 4 weeks (6 weeks in the case of nitrosourea) prior to enrollment date; unless the last therapy consisted of an oral agent whose average half life is known to be less than 48 hours in which case only 2 weeks need to have elapsed. Regardless of the therapy, any toxicity greater than Common Terminology Criteria in Adverse Events (CTCAE) grade 1 from previous anti-cancer therapy must have been resolved.

Last radiotherapy treatment 4 weeks prior to starting treatment with this protocol with the exception of palliative radiotherapy and there must be sites of measurable disease that did not receive radiation.

• Organ and marrow function as defined:
• total bilirubin < 1.5 times the upper limit of reference range (ULRR), unless the patient meets the criteria for Gilbert's Syndrome
• alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) all three < 2.5 times the ULRR, or < 5 times the ULRR if judged by the investigator to be related to liver metastases
• serum creatinine ULRR or creatinine clearance greater than or equal to 50 mL/minute (calculated by Cockcroft-Gault formula or measured in a timed urine collection)
• serum calcium below the CTCAE grade 1 upper limit (11.5mg/dL or 2.9 mmol/L). In cases where the serum calcium is below the normal range, the calcium adjusted for albumin is calculated and substituted for the measured value.
• Serum potassium greater than the lower limit of normal (LLN) and < 5.5 mmol/L.
• Serum magnesium greater than the LLN and < 3.0 mg/dL or 1.23 mmol/L.
• absolute neutrophil count greater than or equal to 1000/mm(3)
• platelet count (Bullet) 100,000/m m(3)
• Prothrombin time (PT) less than or equal to 4 seconds above ULN and partial thromboplastin time (PTT) less than or equal to 10 seconds above ULN.

Ability to understand and sign an informed consent document.

Provision of informed consent prior to any study-related procedures

Negative pregnancy test for women of childbearing potential

Ability and willingness to follow the guidelines of the clinical protocol including visits to NCI, Bethesda, Maryland for treatment and follow up visits.

Because the effects of chemotherapy on the developing human fetus are potentially harmful, female patients must be one year post-menopausal, surgically sterile, or using an acceptable method of contraception during and continued after the last dose of study medications (oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, intrauterine device or tubal ligation). Male patients must be surgically sterile or using an acceptable method of contraception during their participation in this study. Contraceptive use will continue for at least two months after the last dose of study medication.

EXCLUSION CRITERIA

Patients with cancer potentially curable by surgical excision alone or patients who have not received therapy that might be considered standard and potentially curable.

Evidence of severe or uncontrolled systemic disease or any concurrent condition including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, unstable hypertension, seizure disorder, o