Lenalidomide With Gemcitabine in Treatment of Untreated Advanced Carcinoma of the Pancreas

A Phase II Study of Lenalidomide in Combination With Gemcitabine in Subjects With Untreated Advanced Carcinoma of the Pancreas

To evaluate the 6-month overall survival, safety, and tolerability of lenalidomide in combination with standard gemcitabine as first-line treatment for patients with metastatic pancreatic cancer.

Because the activity of lenalidomide addresses numerous mechanisms of carcinoma growth inhibition - including, but not limited to anti-angiogenesis - lenalidomide is being evaluated as part of induction chemotherapy regimens for solid tumors. This phase II study in previously untreated metastatic pancreatic cancer is designed to establish and test the appropriate lenalidomide dose and regimen in combination with gemcitabine.

Inclusion Criteria:

1. Understand and voluntarily sign the informed consent form.

2. Patients >=18 years of age at the time of signing the informed consent form.

3. Ability to adhere to the study visit schedule and other protocol requirements.

4. Histological or cytological documentation of adenocarcinoma of the pancreas, with metastases not amenable to curative surgery or definitive radiation. Patients with locally advanced disease are not eligible.

5. Radiographic or clinical evidence of measurable advanced metastatic pancreatic carcinoma. Patients must have measurable disease according to the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) for target lesions.

6. Previous gemcitabine or 5-fluorouracil (5-FU) with radiation therapy as adjuvant therapy is permitted. Extended use of gemcitabine or 5-FU after completion of adjuvant radiation therapy is not permitted. No prior gemcitabine for metastatic disease or for primary treatment of locally advanced disease is allowed.

7. ECOG performance status of <=2 at study entry.

8. Laboratory test results within these ranges:

   • Absolute neutrophil count (ANC) ≥1,500 cells/mm3 (1.5 x 109/L)
   • Platelet count ≥100,000 cells/ mm3 (100 x 109/L)
   • Serum creatinine <=2.5 mg/dL
   • Total bilirubin <=2.0 mg/dL
   • AST (SGOT) and ALT (SGPT) <=3.0 x ULN or <=5 x ULN if hepatic metastases are present.

9. Prior history of malignancy (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast, or localized prostate cancer with PSA <1.0 ng/mL), unless the patient has been free of disease for >=3 years.

10. All study participants must be registered into the mandatory RevAssist® program, and must be willing and able to comply with the requirements of RevAssist®.

Exclusion Criteria:

1. Prior use of systemic therapy for the treatment of adenocarcinoma of the pancreas, with the exception of 5-fluorouracil or gemcitabine as a radiosensitizer in the adjuvant setting.

2. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form.

3. Pregnant or breast feeding females (lactating females must agree not to breast feed while taking lenalidomide).

4. Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.

5. Surgery or radiation therapy within 14 days of study enrollment as outlined below.

   • Surgery within 14 days of the start of study (patients must have recovered from effects of surgery; 7 days may be considered for minor procedures).
   • Palliative radiation therapy within 14 days of the start of study. The radiation therapy may not be to the only site of measurable disease.

6. Known brain or leptomeningeal disease (CT scan or MRI of the brain required only in case of clinical suspicion of central nervous system involvement).

7. Neuropathy of ≥ grade 2.

8. Known chronic infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and/or Hepatitis C Virus (HCV).