Vorinostat Plus Radiation Therapy in Pancreatic Cancer

Condition(s) targeted: Pancreatic Cancer

Intervention: Radiation (Radiation); Vorinostat (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Sunil Krishnan, MD, Principal Investigator, Affiliation: UT MD Anderson Cancer Center

Overall contact:
Sunil Krishnan Krishnan, MD, Phone: 713-563-2361

Primary Endpoint:

To determine the maximum tolerated dose (MTD) of vorinostat + radiation therapy (RT) in patients with locally advanced pancreatic cancer (LAPC).

Secondary Endpoints:

1. To assess the efficacy of vorinostat + RT in patients with LAPC as estimated by median overall survival.

2. To determine the radiological response as assessed by regular computer tomography (CT) and/or dynamic contrast enhanced computer tomography (DCE-CT) among patients treated with vorinostat and RT.

3. To evaluate the occurrence of symptoms and correlate to disease progression and tolerance to treatment using the MD Anderson Symptom Inventory-Gastrointestinal Module (MDASI-GI) self-reporting tool.

4. To correlate serum cytokine levels with symptoms and treatment outcomes.

Official title: Phase I/II Trial of Vorinostat and Radiation Therapy in Patients With Locally Advanced Pancreatic Cancer

Study design: Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study

Primary outcome: Highest tolerable dose of the chemotherapy drug vorinostat that can be given in combination with radiation therapy to patients with pancreatic cancer.

Detailed description: The Study Drugs:

Vorinostat is designed to interfere with the growth of cancer cells.

Screening Tests:

Signing this consent form does not mean that you will be able to take part in this study. You will have "screening tests" to help the doctor decide if you are eligible to take part in this study. The following tests and procedures will be performed:

- You will have a complete physical exam.

- Blood (about 2 tablespoons) will be drawn for routine tests.

- You will have chest x-rays and computed tomography (CT) scans of the abdomen (stomach

area) and pelvis to check the status of the disease. If chest x-ray results are unclear, a CT scan of the chest will be performed.

- You will have an electrocardiogram (EKG- a test to measure the electrical activity of

the heart) within 10 days of enrollment.

- Women who are able to become pregnant must have a negative urine pregnancy test.

The study doctor will discuss the screening test results with you. If the screening tests show that you are not eligible to take part in the study, you will not be enrolled. Other treatment options will be discussed with you.

Study Drug Dose Level:

If you are found to be eligible to take part in the study, you will begin receiving vorinostat. The dose you receive will be based on how many participants have been enrolled before you, and on the safety data available. The first group of 3 enrolled participants will be given low doses of vorinostat. If no intolerable side effects occur, the next group of 3 will be enrolled at a higher dose level. The study doctor will tell you what dose you will be receiving and how it compares to the doses other participants have received. Up to 3 dose levels will be tested.

Study Drug Administration:

On each day that you receive radiation, you will take vorinostat (as a capsule taken by mouth) in the morning with food.

Radiation:

You will receive radiation once a day on Monday through Friday, except for holidays. This schedule will be continued for 5 1/2 weeks or 28 doses total. Each radiation treatment will usually last about 10-15 minutes.

Study Visits:

Once a week while you are on study, you will have the following tests and procedures performed:

- You will have a physical exam.

- Blood (about 2 teaspoons) will be drawn for routine tests.

- You will be asked about any side effects you may be experiencing.

- You will be asked to keep a record of each day you take vorinostat

Surgical Evaluation:

After completing radiation therapy, you will come back for a follow-up visit about 6-12 weeks later. The following tests and procedures will performed:

- You will have a complete physical exam.

- Blood (about 2 tablespoons) will be collected for routine tests.

- You will have chest x-rays and CT scans of the abdomen and pelvis.

If the doctor thinks that the tumor is removable by surgery at that time, you will have surgery to remove the tumor. You will be given a separate consent form to sign, which will explain the surgery procedure and the risks involved.

Length of Study:

You will remain on study for up to 5 1/2 weeks. You will be taken off-study early if the disease gets worse or intolerable side effects occur.

This is an investigational study. Vorinostat is FDA approved and commercially available. The use of vorinostat for pancreatic cancer and in combination with radiation is investigational. At this time, this combination is being used in research only.

Up to 37 patients will take part in the study. All will be enrolled at M. D. Anderson.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. ECOG performance status of 0 or 1.

2. Patients must be >/= 18 years of age. There will be no upper age restriction.

3. Cytologic or histologic proof of adenocarcinoma of the pancreas. Patients can have tumor originating in any part of the pancreas. Islet cell tumors are not eligible. Only patients with non- metastatic, unresectable disease (AJCC 2002 stage T4 NX M0) are eligible. Patients who cannot undergo resection because of underlying medical problems are also eligible. Patients with regional nodal disease are eligible.

4. All patients must be staged with a physical exam, CXR, and contrast-enhanced helical thin-cut abdominal CT. Unresectability is defined by CT criteria: a) evidence of tumor extension to the celiac axis or superior mesenteric (SM) artery, or b) evidence on either CT or angiogram of occlusion of the SM vein or SM/ portal vein confluence. If a tumor does not meet this definition and is found to be unresectable at surgical exploration, then that tumor is considered unresectable.

5. Patients may have received prior chemotherapy but not prior radiation therapy to the upper abdomen.

6. Bone marrow function: absolute neutrophil count (ANC) >1,500/ul. Platelets >100,000/ul.

7. Hepatic function: Total bilirubin less than 1. 5mg/dL. If the patient required an endobiliary stent and/or external biliary drain, the bilirubin level must have declined on consecutive measurements indicating adequate biliary decompression; alanine aminotransferase (ALT) 8. Renal function: BUN 9. Patients must be willing to sign informed consent indicating that they are aware of the investigational nature of the study, and are aware that participation is voluntary.

Exclusion Criteria:

1. Prior abdominal radiotherapy.

2. Participation in any other experimental drug study in the 30 days preceding initiation of treatment on the current study.

3. Prior treatment with HDAC inhibitors (except valproic acid with a 30-day washout period)

4. Prior history of cancer within the last five years except for basal cell carcinoma of the skin or carcinoma in situ of the cervix. Patients with previous malignancies but without evidence of disease for 5 years will be allowed to enter the trial.

5. Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Women / men of childbearing potential not using a reliable contraceptive method (oral contraceptive, other hormonal contraceptive, intrauterine device, diaphragm or condom). (Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential). Patients must agree to continue contraception for 30 days from the date of the last study drug administration.

6. Serious, uncontrolled, concurrent infection(s) requiring IV antibiotics or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy.

7. Current treatment of active hepatitis virus or HIV infection with interferon, ribavirin, telbivudine, entecavir, lamivudine, adefovir, efavirenz, zidovudine, tenofovir, emtricitabine, or ritonavir.

8. Psychiatric disorders rendering patients incapable of complying with the requirements of the protocol.

9. Inability to comply with study and/or follow-up procedures.

Sunil Krishnan Krishnan, MD, Phone: 713-563-2361

UT MD Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Sunil Krishnan, MD, Principal Investigator

UT MD Anderson Cancer Center

Starting date: May 2009
Last updated: May 11, 2009