Vorinostat Plus Radiation Therapy in Pancreatic Cancer

Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00831493
• Other study ID #: 2008-0780
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: January 27, 2009
• Last updated: February 27, 2012
• Start date: May 2009
• Est. completion date: October 2010

Study information

• Verified date: February 2012
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Description:

The Study Drugs:

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

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.

Surgical Evaluation:

After completing radiation therapy, you will come back for a follow-up visit about 6-12 weeks later.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (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 (American Joint Committee on Cancer (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, chest x-ray/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) </= 5 times the upper limit of normal.

8. Renal function: Blood urea nitrogen (BUN) </= 30 mg% and creatinine </= 1.5 mg%

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 intravenous (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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Radiation:
• Chemoradiation (Radiation Therapy)
Dose of 50.4 Gy in 1.8 Gy fractions in 28 fractions, Monday to Friday, Weeks 1 to 6.

Drug:
• Vorinostat
Starting Dose of 200 mg orally once daily, Monday to Friday, Weeks 1 to 6.

Locations

Country	Name	City	State
United States	UT MD Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) of Vorinostat + Chemoradiation	MTD is maximum dose at which 6 patients are treated and there is at most 1 patient with dose limiting toxicities (DLT). Toxicities graded according to the Common Terminology Criteria for Adverse events (CTCAE).	Toxicity assessment at 6 weeks following chemoradiation (6 weeks)	Yes

External Links

•   UT MD Anderson Cancer Center