Patient case: 54-year-old male with Gastric cancer. Genetic variant: PIK3CA (E545K). Other conditions: Depression.

Clinical trial: Open Label, Multi-center Study to Assess the Safety, Tolerability and Pharmacokinetics of CUDC-907 in Subjects With Advanced/Relapsed Solid Tumors

Summary: This is a Phase I, open-label, multi-center trial designed to evaluate the safety, tolerability and pharmacokinetics of CUDC-907 administered orally to subjects with advanced/relapsed solid tumors.

Detailed description: This is a Phase I, open-label, multi-center trial designed to evaluate the safety, tolerability and pharmacokinetics of CUDC-907 administered orally to subjects with advanced/relapsed solid tumors. The following dosing schedules may be examined, each consisting of 21-day treatment cycles:
  1. Three days weekly on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 (TIW schedule).
  2. Five days on/two days off on Days 1 to 5, 8 to 12, and 15 to 19 (5/2 schedule).
  3. Four days on/three days off on Days 1 to 4, 8 to 11, and 15 to 18 (4/3 schedule).

Eligibility: Inclusion Criteria:
  1. Subjects ≥18 years of age
  2. Histopathologically confirmed diagnosis of advanced solid tumor such as breast cancer or midline carcinoma with NUT rearrangement, that has progressed despite standard therapy, or for which no standard therapy exists. In the case of breast cancer, this must be ER+ or PR+, Her2 negative disease (women only) with disease progression on at least one prior hormonal therapy for advanced/metastatic disease or disease relapse while on adjuvant hormonal therapy
  3. Measurable or evaluable disease
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  5. Recovery to Grade 1 or baseline of any toxicity due to prior systemic treatments or radiotherapy (excluding alopecia). Note: for subjects with HR+/Her2 negative breast cancer only: ongoing treatment with any of the following: tamoxifen, anastrozole, exemestane or letrozole is allowed
  6. Adequate hematologic and organ function as evidenced by the following laboratory studies within two weeks (14 days) of study enrollment: Absolute neutrophil count 1,500/L; platelets 100,000/L; hemoglobin >9 g/dL; creatinine 1.5x upper limit of normal (ULN); total bilirubin (Tbili) 1.5x ULN; aspartate aminotransferase/alanine aminotransferase (AST/ALT) 2.5x ULN; serum albumin >3 g/dl; partial thromboplastin time or INR <1.2 x ULN (unless receiving therapeutic anticoagulation)
  7. For subjects with diabetes, adequate blood sugar control as evidenced by a hemoglobin A1c value <8%
  8. Women of child-bearing potential must have a negative serum or urine pregnancy test
  9. Men and women of child-bearing potential must agree to use adequate birth control throughout their participation in the study and for 30 days following the last study treatment
  10. Able to provide written informed consent and follow protocol requirements
  Exclusion Criteria:
  1. Systemic anticancer therapy within three weeks of study entry, except for nitrosoureas or mitomycin C within six weeks
  2. Radiotherapy within one week prior to starting study treatment
  3. Other investigational agent(s) within 21 days prior starting to study treatment
  4. Symptomatic central nervous system (CNS) involvement or lymphangitic metastasis. Stable or improving CNS disease that is not under active treatment after receipt of adequate therapy is allowed
  5. Uncontrolled or severe cardiovascular disease, including myocardial infarction or unstable angina within six months prior to study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease or cardiac amyloidosis
  6. Diabetes mellitus uncontrolled by medication
  7. Ongoing diarrhoea defined as more than one watery stool/day
  8. Serious infection requiring systemic antibiotic therapy within 14 days prior to study treatment
  9. Immunosuppressive medication within 7 days prior to first dose of CUDC-907. Inhaled and topical corticosteroids are permitted, as is replacement dosing of steroids (defined as <30 mg/day hydrocortisone or the equivalent) provided that the subject has been on a stable or tapering dose for at least 14 days prior to the first dose of CUDC-907
  10. Second primary malignancy within two years of study entry that requires active treatment
  11. Known gastrointestinal condition that would interfere with swallowing or oral absorption/tolerance of CUDC-907
  12. Known positive status for human immunodeficiency virus (HIV) or hepatitis B surface antigen, or known or suspected hepatitis C infection
  13. Pregnancy or ongoing breast-feeding status
  14. Unstable or clinically significant concurrent condition (e.g. medical or psychological) that would, in the opinion of the investigator, jeopardize subject safety and/or compliance with the protocol

Relevance to patient case: not relevant