Ensayos clínicos

Inclusion Criteria

• Adult males and females, age ≥ 18 years.
• Cohort I (Dose Escalation)
  • histologic or cytologic proof of any solid tumor that is incurable with no standard therapy that is likely to make a major impact on clinical outcomes.  
• Cohort II (MTD)
  • Metastatic adenocarcinoma of the pancreas. Prior systemic treatment for metastatic disease is allowed.
  • Patient is thought to be a short- or long-term candidate for gemcitabine in the opinion of the treating oncologist.
  • Weight loss of > 5% at any point after a cancer diagnosis or within 3 months prior to this cancer diagnosis. No documentation from the medical record is necessary
  • Patient willing to undergo muscle biopsies at baseline and after 28 to 35 days of tofacitinib therapy as required by the protocol
  • Patient willing to have paraffin-embedded slides of the primary pancreas tumor or metastatic site, if available, sent to Mayo investigators for this study   
• Laboratory values obtained ≤ 7 days prior to registration:
  • ANC ≥ 1500/mm3
  • Platelet ≥ 100,000/ mm3
  • Total bilirubin ≤ 2 x upper limit of normal (ULN)
  • AST (SGOT) ≤ 3 x ULN
  • Creatinine ≤ 1.5 x ULN
  • Hemoglobin  ≥ 9.0 g/dL  
  • Cohort II (MTD) only PT/INR  ≤ 1.5 x ULN
• Ability to provide written informed consent
• Willing to return to Mayo Clinic for follow up
• Life expectancy ≥ 12 weeks
• ECOG performance status (PS) 0, 1 or 2
• Able to swallow or have medication administered through a G-tube and absorb the medication
• Patient willing to complete a  medication diary.
• Agree to use acceptable form of contraception during the study and for up to 30 days after last study drug dose if female partner is of childbearing potential
  • Acceptable forms of contraception:
    • Latex condom (always used with spermicide)
    • Diaphragm (always used with spermicide)
    • Cervical cap (always used with spermicide)
  • Acceptable forms of secondary contraception, when used along with a barrier method:
    • Hormonal contraception methods, including pills, patches, rings, or injections except progestin-only containing pills (i.e. “Mini-pill”)
    • Tubal ligation
    • Partner’s vasectomy
    • Intrauterine device (non-progesterone T)
    • Vaginal sponge (containing spermicide)
  • Other acceptable forms:
    • 100% commitment to abstinence
• Women of childbearing potential must have a negative urine or serum pregnancy test done ≤ 7 days prior to registration.

Exclusion Criteria

• Unacceptable forms of contraception for women of childbearing potential:
  • Oral contraception containing progestins only
  • IUD progesterone T
  • Female condom
  • Natural family planning (rhythm method) or breastfeeding
  • Fertility awareness
  • Withdrawal
  • Cervical shield
• Known standard therapy for the patient’s disease that is potentially curative
• Uncontrolled intercurrent illness including, but not limited to
  • ongoing or active infection, including localized infections
  • symptomatic congestive heart failure
  • unstable angina pectoris
  • cardiac arrhythmia 
  • psychiatric illness/social situations that would limit compliance with study requirements.
• Untreated brain metastases
• Pregnant women
• Nursing women
  • This study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
• Other concurrent chemotherapy, immunotherapy, radiotherapy, any ancillary therapy considered investigational (utilized for a non-FDA-approved indication and in the context of a research investigation) 
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
• Prior history of tuberculosis or positive Purified Protein Derivative (PPD) test result 
• Prior history of hepatitis B or hepatitis C.
• Administration of live vaccines ≤ 14 days prior to registration
• Immunocompromised patients or patients receiving immunosuppressant agents ≤ 30 days prior to registration
• Receiving any medications or substances that are strong inhibitors of CYP450 3A4 ≤ 7 days prior to registration
  • Indinavir
  • Nelfinavir
  • Ritonavir
  • Clarithromycin
  • Itraconazole
  • Ketoconazole
  • Nefazodone
  • Saquinavir
  • Telithromycin
• Receiving any medications or substances that are inducers of CYP450 3A4 ≤ 7 days prior to registration.
  • Efavirenz
  • Nevirapine
  • Carbamazepine
  • Modafinil
  • Phenobarbital
  • Phenytoin
  • Pioglitazone
  • Rifabutin
  • Rifampin
  • St. John’s wort