| Inclusion Criteria: | 1) Patient must have histologically or cytologically confirmed advanced malignancies, except all forms of leukemia, for which standard curative or palliative measures do not exist, are no longer effective, or are not acceptable to the patient.
2) For the dose escalation part of the study, at screening, every effort will be made to acquire patient's archival tumor tissue samples obtained at the time of the original cancer diagnosis. If not available, fresh tumor tissue may be obtained at the discretion of PI.
3) For the "tail" portion, sarcoma patients with wt p53 as determined by AmpliChip analysis on FFPE tumor tissue sample obtained from fresh tumor biopsy during screening or from Archival tumor tissue. Archival tumor tissue to determine p53 mutation status may only be used if the patient has NOT received ANY antitumor therapy in between the time the tissue was collected and the start of study. A fresh tumor biopsy will still be required for biomarker analyses prior to the start of study medication for patients in which archival tumor tissue was used to determine p53 mutation status.
4) Ability to understand and the willingness to sign a written informed consent form.
5) Life expectancy of >/= 12 weeks.
6) Able to comply with all aspects of the protocol, as determined by the PI.
7) Age >/= 18 years.
8) ECOG performance status of 0 to 1.
9) Female patients with child-bearing potential must have a negative pregnancy test within the seven days before the study first drug administration.
10) Patient must be willing to use effective methods of contraception. Female patients must be postmenopausal, surgically sterile, or they must agree to use a physical barrier method of contraception. Oral or injectable contraceptive agents can not be the sole method of contraception. Male patients must be surgically sterile or agree to use acceptable method of contraception.
11) There are no limitations on additional, allowable type and amount of prior therapy. Acute toxicities from any prior therapy, surgery, or radiotherapy must have resolved to NCI-CTCAE Grade </= 1. The last dose of prior therapy must be >/= 21 days prior the first administration of study drug R7112 (this would satisfy the recognized requirement of at least 5 times the terminal half-life period for most drugs currently used, including most of the RTK inhibitors).
12) Adequate bone marrow function as defined by: ANC of >/= 1.5 x 10^9/L. Platelets count of >/= lower limit of normal. Hemoglobin of >/= 9.0 g/dl.
13) Adequate hepatic function assessed by: Serum total bilirubin </= 2 mg/dl, unless resulting from hemolysis. AST/ALT </= 2.5 x institutional ULN (or </= 5 x ULN if liver metastases).
14) Adequate renal function assessed by: Serum creatinine within reference lab normal limits, or creatinine clearance (by Cockcroft Gault formula, >/= 50 ml/min for patients in whom, in the PI judgment, serum creatinine level may not adequately reflect renal function).
15) Patients with prior CNS metastases that have had therapy, are off steroids and asymptomatic, are eligible.
16) Patients with chronic, stable, rate-controlled, atrial fibrillation are eligible. |