Phase I Study of Vorinostat and Sorafenib in Advanced Cancer

Inclusion Criteria

• •Parts A: Histologically or cytologically documented solid tumor malignancy or non-Hodgkin's lymphoma (Part B: renal cell carcinoma, Part C: non-small cell lung carcinoma) with clinical evidence of advanced and/or metastatic disease, which is refractory to established forms of therapy or for which no effective therapy exists, or for which sorafenib alone would be considered by the investigator as an appropriate therapy; patients who have refused available standard therapies would also be deemed eligible
• •In Part A, evaluable disease by radiology and/or a recognized serum tumor marker is required; in Parts B and C, measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) is required
• •Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
• •Predicted life expectancy ≥ 12 weeks
• •Patients may have had prior therapy, providing the following conditions are met:
• •* Patients must have recovered from any treatment related toxicities (with the exception of alopecia) to ≤ CTC grade 1 (fatigue, and neurotoxicity at grade 2 are permissible if stable for \> 3 months) prior to registration
• •* Chemotherapy: A minimum of 5 predicted half-lives of the agent must have elapsed between the end of treatment and registration on to the study; when half-lives are not available the principle of 2 weeks for once daily medications and 3 weeks for agents given less frequently will be adopted, but discussion with the principal investigator is recommended
• •* Hormonal therapy: Patients may have had prior anticancer hormonal therapy provided it is discontinued \> 4 weeks prior to registration into the study; however, patients with prostate cancer with evidence of progressive disease may continue on therapy which produces medical castration (eg, goserelin or leuprorelin) provided this was commenced at least three months earlier
• •* Radiation: Patients may have had prior radiation therapy that has not exceeded 25% of bone marrow reserve provided that they have recovered from the acute, toxic effects of radiotherapy prior to registration; a minimum of 7 days must have elapsed between the end of radiotherapy to non-target lesions and registration into the study (minimum of 28 days for target lesions)
• •* Surgery: Previous surgery is permitted provided that wound healing has occurred prior to registration
• •Supportive therapy including bisphosphonates is permissible; previous use of myeloid and erythroid growth factor support is permissible, but not within 2 weeks of commencement of study; primary prophylactic use of myeloid and erythroid growth factors is not permitted within the study, but intervention or secondary prophylaxis is permitted if instituted following the documentation of ≥ grade 3 neutropenia or ≥ grade 2 anemia (hemoglobin)
• •International Normalized Ratio (INR) \< 1.5 or a prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits; patients receiving anticoagulation treatment with an agent such as warfarin or heparin may be allowed to participate; for patients on warfarin, the INR should be measured prior to initiation of sorafenib/vorinostat and monitored at least weekly, or as defined by the local standard of care, until INR is stable; vorinostat and sorafenib have both been reported to elevate INR in those on coumadin derivatives
• •Neutrophil count ≥ 1.5 x 10\^9/L
• •Platelet count ≥ 75 x 10\^9/L
• •Bilirubin ≤ 1.5 x Upper limit of normal (ULN)
• •Aspartate aminotransferase (AST) and/or alanine transaminase (ALT) ≤ 2.5 x ULN (ie, ≤ CTC grade 1) or ≤ 5 x Upper limit of normal (UNL) if patient has documented liver metastases (ie, ≤ CTC grade 2)
• •Serum creatinine ≤ 1.5 x ULN
• •Patient must be accessible for repeat dosing and follow-up
• •Patients - both males and females - with reproductive potential (ie, menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures throughout the study; women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration
• •Patients must provide verbal and written informed consent to participate in the study, including pharmacokinetic sampling