Crolibulin and Cisplatin in Treating Patients with Recurrent or Metastatic Solid Tumors That Cannot Be Removed by Surgery

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 ATC, including ATC as part of a thyroid carcinoma of another histologic subtype
• Measurable disease at presentation with disease measurable by 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
• 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 for 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
• Total bilirubin < 1.5 x 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 x ULRR, or < 5 x ULRR if judged by the investigator to be related to liver metastases
• Serum creatinine =< ULRR or creatinine clearance >= 50 mL/minute (calculated by Cockcroft-Gault formula or measured in a timed urine collection)
• Serum calcium below the CTCAE grade 1 upper limit (11.5 mg/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 >= 1000/mm^3
• Platelet count >= 100,000/mm^3
• Prothrombin time (PT) =< 4 seconds above upper limit of normal (ULN) and partial thromboplastin time (PTT) =< 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
• 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, or psychiatric illness – which in the Investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol
• Untreated brain metastases (or local treatment of brain metastases within the last three months)
• During Phase II enrollment: prior therapy with cisplatin with the exception of when given concurrently with radiation therapy (cisplatin will be allowed as prior therapy during Phase I enrollment)
• Women who are currently pregnant or breast-feeding
• During Phase II enrollment: the presence of a second malignancy within the last 2 years, other than squamous cell carcinoma of the skin or in situ cervical cancer; cancer survivors who have been free of disease for at least two years can be enrolled in this study
• Patients with evidence of a bleeding diathesis that cannot be corrected with standard therapy or factor replacement
• Any unresolved toxicity greater than CTCAE grade 1 (except alopecia, and certain other unresolved CTCAE grade 2 toxicities including bone marrow hypocellularity, lymphopenia, infusion-related reaction, infusion site extravasation, injection site reaction, portal vein hypertension, obesity) from previous anti-cancer therapy; patients with grade 1 neuropathy will be evaluated on a case by case basis for entry into study; pre-chemotherapy medical conditions will be taken into consideration
• Major surgery with incompletely healed surgical incision before starting study therapy
• Clinically significant cardiovascular event (e.g. myocardial infarction, superior vena cava syndrome [SVC], New York Heart Association [NYHA] classification of heart disease >= 2 within 3 months before entry); or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia
• History of arrhythmia (multifocal premature ventricular contractions PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia; atrial fibrillation, controlled on medication, is not excluded
• Patients with a left ventricular ejection fraction less than the institutional lower limit of normal
• History (within the last 6 months) or presence of stroke/cerebrovascular accident
• Corrected QT (QTc) prolongation with other medications; if the medication can be discontinued and an alternative medication started that does not cause QTc prolongation, the patient would be eligible; if no alternative medication is available and the medication cannot be discontinued for medical reasons, then the patient would not be eligible
• Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age
• Presence of left bundle branch block (LBBB)
• QTc with Fridericia’s correction that is not measurable, or >= 480 msec on screening electrocardiogram (ECG); (Note: if a patient has a QTc interval >= 480 msec on screening ECG, the screen ECG may be repeated twice [at least 24 hours apart]; the average QTc from the three screening ECGs must be < 480 msec in order for the patient to be eligible for the study); patients who are receiving a drug that has a risk of QTc prolongation are excluded if QTc is >= 460 msec
• Concurrent medication that may cause QTc prolongation or induce Torsades de Pointes
• Crolibulin is a substrate of cytochrome P450 (CYP)2C8, CYP2C9, CYP2C19 and CYP3A4; strong inducers and inhibitors of these enzymes will constitute concomitant medications that are prohibited during the study; these medications include but are not limited to: for CYP2C8, montelukast and trimethoprim, for CYP2C9, lovastatin and sertraline, for CYP2C19, fluoxetine, ketoconazole, pantoprazole, omeprazole, rabeprazole, and ticlopidine, for CYP3A4, itraconazole, clarithromycin, erythromycin, telithromycin, and verapamil
• Hypertension not controlled by medical therapy (systolic blood pressure greater than 150 mm Hg or diastolic blood pressure greater than 100 mm Hg)