A Clinical Research Study to Determine Whether PD 0332991 May Be Effective in Treating Patients With Liver Cancer
Condition: Advanced Hepatocellular Carcinoma; HCC; Liver Cancer
MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms
Intervention: PD-0332991
Intervention description: PD-0332991, 125mg, 3 cycles
Intervention MeSH terms: Palbociclib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced Hepatocellular Carcinoma; HCC; Liver Cancer; PD-0332991

Summary:

      This is a Phase 2 Study of PD-0332991 in the treatment of patients with Advanced
      Hepatocellular Carcinoma (HCC), a type of adenocarcinoma and the most common type of liver
      tumor. PD-0332991 is a compound that stops the tumor cell from entering the Synthesis phase
      of the cell cycle, therefore stopping DNA multiplication and decreased tumor cell copying.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female, age > or = 18 years with HCC refractory to currently available
             therapies.

          2. Documented HCC by at least 2 out of 3 mentioned criteria and evidence of
             non-resectability by a multidisciplinary team:

             A. Radiological - MRI with arterial enhancement and rapid venous washout B. Biopsy C.
             Serum alpha-fetoprotein level > or = 200

          3. Positive staining for RB-function on tumor biopsy.

          4. Subject must be able to give written informed consent and be able to follow protocol
             requirements

          5. Life expectancy greater than 3 months

          6. Be Child's-Pugh class A or B

          7. ECOG Performance status of < or = 2

          8. If female of childbearing potential must have negative pregnancy test at screening and
             may not be breast-feeding

          9. Females of child-bearing potential (< one year post-menopausal with documented FSH
             greater than 30 IU/L or surgically not sterile), must agree to practice an effective
             method of avoiding pregnancy (including oral or implanted contraceptives, intrauterine
             device, condom, diaphragm with spermicidal, cervical cap, abstinence or sterile sex
             partner) from the time informed consent is signed through follow-up. Males must agree
             to take appropriate precautions to avoid fathering a child from screening through
             follow-up.

         10. No other active malignancy requiring treatment in the last 3 years other than
             adequately treated non-melanomatous skin cancer, adequately treated cervical carcinoma
             in-situ, superficial adequately treated bladder cancer or prostatic intraepithelial
             neoplasia without evidence of prostate cancer.

         11. Adequate bone marrow, liver and renal function as assessed by the following:

             A. Hemoglobin > or = 8 g/dL B. WBC > or = 4,000/uL C. Absolute neutrophil count > or =
             1,500/uL D. Platelets > or = 75,000/uL E. Total bilirubin < or = 1.5 times ULN F. ALT
             and AST < or = 5 times ULN G. Creatinine < or = 1.5 times ULN H. Albumin > or = 2.5
             mg/dL

         12. Subjects who have received previous radiotherapy, loco-regional, or systemic therapy
             are eligible. A minimum interval of 4 weeks since the last anti-cancer treatment of
             any kind is required.

         13. Subjects with brain metastases or a history of previously treated brain metastasis are
             eligible but must:

        A. Have been treated by surgery or stereotactic radiosurgery (SRS) at least 4 weeks prior
        to enrollment B. AND have a baseline MRI or CT that shows no evidence of active
        intercranial disease C. AND be off steroids for at least 1 week prior to study enrollment

        Exclusion Criteria:

          1. Any concurrent active malignancy requiring treatment (other than basal or squamous
             cell carcinoma of the skin, carcinoma in situ of the cervix, superficial bladder
             tumors, or other malignancies curatively treated > 3 years prior to study entry)

          2. History of severe cardiovascular disease within the last 12 months: symptomatic
             congestive heart failure, myocardial infarction, coronary artery disease (CAD), life
             threatening arrhythmias, uncontrolled hypertension

          3. Renal failure requiring hemo- or peritoneal dialysis

          4. Unstable systemic diseases or active uncontrolled infection

          5. Known history of HIV infection

          6. Clinically significant gastrointestinal bleeding within 30 days prior to study entry

          7. Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to
             study entry

          8. Child's-Pugh Class C

          9. Any malabsorption problem that, in the investigator's opinion, would prevent adequate
             absorption of the study drug

         10. Presence of any other medical complications that in the investigator's opinion,
             suggests a survival of < 3 months

         11. Substance abuse, or medical, psychological or social conditions that may interfere
             with the patient's participation in the study or evaluation of the study results

         12. Patient inability to swallow oral medications

         13. Any condition that is unstable or which could jeopardize the safety of the patient and
             his/her compliance in the study

         14. Pregnant or breast-feeding patients

         15. Being of reproductive potential and unable or unwilling to practice an effective
             contraceptive method

         16. Lack of positive staining for RB-function on tumor biopsy.