OK-1 (SHetA2) for the Treatment of Advanced or Recurrent Solid Tumors

Inclusion Criteria

• Patients must have histologic diagnosis of recurrent solid tumor which has progressed through available therapies with expected survival benefit
• Absolute neutrophil count (ANC) greater than or equal to 1500/mcl. This ANC cannot have been induced or supported by granulocyte colony stimulating factors
• Platelets greater than or equal to 150,000/mcl., not transfusion dependent
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L; not transfusion dependent
• Creatinine =< 1.5 x institutional upper limit normal (ULN) or calculated creatinine clearance >= 60 mL/min using Cockcroft-Gault equation for patients with creatinine levels > 1.5 x institutional ULN
• Bilirubin =< 1.5 x ULN OR direct bilirubin =< 1 x ULN
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3.0 x ULN, unless liver metastases are present, in which case they must be =< 5 x ULN
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. Patients on anti-coagulant therapies will not be excluded unless clinically relevant
• Neuropathy (sensory and motor) less than or equal to grade 1. Patients should be free of active infection requiring parenteral antibiotics or a serious uncontrolled medical illness or disorder within four weeks of study entry
• Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration. Continuation of hormone replacement therapy is permitted
• Patients must have a performance status score of 0-2 by Eastern Cooperative Oncology Group (ECOG) criteria
• Patients of childbearing potential must have a negative pregnancy test prior to the study entry and be practicing an effective form of contraception. If applicable, patients must discontinue breastfeeding prior to study entry. Pregnancy tests will be required before starting every cycle of OK-1. The acceptable methods of birth control are listed below and should be used while on the study and for 3 months afterwards * Acceptable methods of birth control include: * An approved oral contraceptive (birth control pill) * Intra-uterine device (IUD) * Hormone implants * Contraceptive injection (Depo-Provera) * Barrier methods (diaphragm with spermicidal gel or condoms) * Transdermal contraceptives (birth control patch) * Vaginal contraception ring (birth control ring) * Sterilization (tubal ligation, hysterectomy, or vasectomy)
• Patients must have satisfactory results for the baseline laboratory analyses and diagnostic procedures as specified in the protocol
• Patients must have signed an Institutional Review Board (IRB)-approved informed consent and authorization permitting release of personal health information
• Patients must be at least 18 years old
• Patients in all cohorts must have a fresh pre-treatment tumor biopsy. Archival tissue is permitted when biopsy collection is optional for patients enrolled on dose level 2 and 3. Biopsies are mandatory on cohort 4 and/or expansion. When a biopsy is mandatory, additional archival tissue may be collected for analysis, if available
• Patients must be willing to have fresh biopsy taken post-cycle 1 treatment (optional only for patients enrolled on dose level 2 and 3; Biopsies are mandatory for patients enrolling on Cohort 4 and/or dose expansion phase.)
• Life expectancy of at least 3 months
• Patients must be able to take oral medications
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

Exclusion Criteria

• Unable to take oral medications
• Patients of childbearing potential not practicing adequate contraception, patients who are pregnant, or patients who are breastfeeding are not eligible for this trial
• Patients who are pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to OK-1
• A diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Patients receiving treatment for active autoimmune disease. “Active” refers to any condition currently requiring therapy. Examples of autoimmune disease include systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease and rheumatoid arthritis. (note if steroid use is < 10 mg/day prednisolone equivalent and patient has stable symptoms they may be allowed on study with discussion with the medical monitor)
• Patients with a prior or concurrent malignancy whose natural history or treatment does have the potential to interfere with the safety or efficacy assessment of the investigational regimen are NOT eligible for this trial
• Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid [HCV RNA] [qualitative] is detected). Ongoing systemic bacterial, fungal, or viral infection; known human immunodeficiency virus (HIV) infection with positive viral load or acquired immunodeficiency syndrome (AIDS)-related illness. Patients with HIV and a negative viral load are allowed on study
• Patients with concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study * NOTE: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging (using the identical imaging modality for each assessment, either magnetic resonance imaging [MRI] or computed tomography [CT] scan) for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. Carcinomatous meningitis precludes a patient from study participation regardless of clinical stability
• Patients taking concomitant therapy with any of the following: other non-study cytotoxic chemotherapy; other investigational therapies
• Currently participating and receiving study therapy, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Prior chemotherapy or targeted small molecule therapy within 4 weeks, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent * Note: Patients with =< grade 2 neuropathy or =< grade 2 alopecia are an exception to this criterion and may qualify for the study * Note: If the patient underwent major surgery, she must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Prior bone marrow/hematopoietic stem cell transplantation
• History of solid organ, bone marrow, or progenitor cell transplantation
• History of major surgical procedure within 28 days prior to start of study treatment