Ensayos clínicos

Inclusion Criteria

• Histologic proof of cancer that is now unresectable
• Metastatic solid tumors refractory to available therapy or for whom standard systemic therapy does not exist
• Absolute neutrophil count (ANC) ≥ 1500/μL
• Platelets (PLT) ≥ 100,000/μL
• Total bilirubin ≤ upper limits of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x ULN
• Creatinine ≤ 1.25 x ULN
  • If above 1.25 x ULN calculated creatinine clearance must be ≥ 60 ml/min
• Hemoglobin (Hgb) ≥ 9.0 g/dl
• Normal diffusing capacity of the lung for carbon monoxide (DLCO) or the presence of an asymptomatic grade 1 DLCO
  • DLCO must be corrected for hemoglobin
• Ability to provide informed consent
• Willing to return to Mayo Clinic for follow-up
• Life expectancy ≥ 12 weeks
• Willing to provide the biologic specimens (blood and urine) as required by the protocol
• Cohort II (MTD) only
  • Breast, ovarian, peritoneal or renal cell carcinoma
  • Tumor that is amenable for biopsy taken during Cycle 1 at 24 +/- 4 hours following the end of AFP-464 infusion
  • International normalized ratio (INR) ≤ 1.4
  • If taking aspirin, must discontinue ≥ 5 days prior to procedure
  • If receiving IV Heparin, must discontinue 4 hours prior to the procedure and an APTT measurement obtained if clinically indicated
  • If receiving subcutaneous or low molecular weight heparin must discontinue for 8 hours prior to procedure

Exclusion Criteria

• A known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 3 or 4
• Prior thoracic radiotherapy
• Symptomatic pulmonary disease
• Uncontrolled intercurrent illness including, but not limited to
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Seizure disorder
  • Psychiatric illness/social situations that would limit compliance with study requirements
• Any of the following prior therapies
  • Chemotherapy ≤ 4 weeks prior to study entry
  • Mitomycin C/nitrosoureas ≤ 6 weeks prior to study entry
  • Immunotherapy ≤ 4 weeks prior to study entry
  • Biologic therapy ≤ 4 weeks prior to study entry
  • Radiation therapy ≤ 4 weeks prior to study entry
  • Radiation to > 25% of bone marrow
• Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
• Uncontrolled brain metastases
  • Brain metastases are not permitted on study unless the metastases have been treated by surgery or radiotherapy, and the patient has been neurologically stable and off steroids for ≥ 4 weeks
• Any of the following
  • Pregnancy
  • Females of childbearing potential must have a negative serum pregnancy test ≤ 7 days prior to registration
  • Nursing
  • Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], or abstinence, etc.) prior to study entry and for the duration of study participation
  • If a woman becomes pregnant or suspects she is pregnant while participating in this study, she should inform her treating physician immediately
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AFP464
• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-FDA-approved indication and in the context of a research investigation)
• Human immunodeficiency virus (HIV)-positive, and on combination antiretroviral therapy
• Active smokers and those who have smoked ≤ 30 days prior to registration, and unwilling or unable to refrain completely from smoking while on study