Vorinostat Plus Radiation Therapy in Pancreatic Cancer

NCT00831493 | Terminated Phase 1 Results

• 1 other identifier: 2008-0780
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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. 1.To assess the efficacy of vorinostat + RT in patients with LAPC as estimated by median overall survival.
2. 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. 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. 4.To correlate serum cytokine levels with symptoms and treatment outcomes.

Conditions

Pancreatic Cancer

Keywords

Pancreas; Pancreatic Cancer; Locally Advanced Pancreatic Cancer; LAPC; Non-Metastatic; Unresectable; Vorinostat; XRT; RT; Radiation Therapy; SAHA; Suberoylanilide Hydroxamic Acid; MSK-390

Outcome Measures

Primary Outcomes (1)

• 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)

Study Arms (1)

Vorinostat + Radiation Therapy

EXPERIMENTAL

Vorinostat starting dose 200 mg orally once daily, Monday to Friday, Weeks 1 to 6; Radiation Therapy Dose of 50.4 Gray (Gy) in 1.8 Gy fractions in 28 fractions, Monday to Friday, Weeks 1 to 6.

Radiation: Chemoradiation (Radiation Therapy); Drug: Vorinostat

Interventions

Chemoradiation (Radiation Therapy) RADIATION

Dose of 50.4 Gy in 1.8 Gy fractions in 28 fractions, Monday to Friday, Weeks 1 to 6.

Also known as: XRT, RT

Vorinostat + Radiation Therapy

Vorinostat DRUG

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

Also known as: SAHA, Suberoylanilide Hydroxamic Acid, MSK-390

Vorinostat + Radiation Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Patients must be \>/= 18 years of age. There will be no upper age restriction.
• 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.
• 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.
• Patients may have received prior chemotherapy but not prior radiation therapy to the upper abdomen.
• Bone marrow function: absolute neutrophil count (ANC) \>1,500/ul. Platelets \>100,000/ul.
• 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.
• Renal function: Blood urea nitrogen (BUN) \</= 30 mg% and creatinine \</= 1.5 mg%
• 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.

You may not qualify if:

• Prior abdominal radiotherapy.
• Participation in any other experimental drug study in the 30 days preceding initiation of treatment on the current study.
• Prior treatment with HDAC inhibitors (except valproic acid with a 30-day washout period)
• 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.
• 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.
• 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.
• Current treatment of active hepatitis virus or HIV infection with interferon, ribavirin, telbivudine, entecavir, lamivudine, adefovir, efavirenz, zidovudine, tenofovir, emtricitabine, or ritonavir.
• Psychiatric disorders rendering patients incapable of complying with the requirements of the protocol.
• Inability to comply with study and/or follow-up procedures.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Chemoradiotherapy; Radiotherapy; Vorinostat

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Sunil Krishnan, MD / Associate Professor
• Organization: UT MD Anderson Cancer Center

mclemons@mdanderson.org

Study Officials

• Sunil Krishnan, MD

  UT MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2009
• First Posted: January 29, 2009
• Study Start: May 1, 2009
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: February 28, 2012
• Results First Posted: February 24, 2012

Record last verified: 2012-02

Locations

US (1)