Phase I Study of Gemcitabine, Sorafenib and Radiotherapy in Patients With Unresectable Pancreatic Cancer

NCT00375310 | Completed Phase 1 DMC

• 1 other identifier: 0607-09; IUCRO-0155
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of the combined treatment of Sorafenib (BAY 43-9006) with Gemcitabine and radiotherapy in patients with localized unresectable pancreatic cancer.

Conditions

Pancreatic Cancer; Adenocarcinoma of the Pancreas

Keywords

Phase I; Pancreas Cancer; Chemo-radiotherapy

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety and tolerability of the combined treatment with Gemcitabine with Sorafenib and radiotherapy in patients with localized unresectable pancreatic cancer.

  completion of study

Secondary Outcomes (6)

• To evaluate the response rate (CR + PR), clinical benefit (CR + PR + SD) and tumor shrinkage (CR + PR + SD that shrinks) of Gemcitabine with Sorafenib and radiotherapy

  completion of study

• To evaluate time to disease progression and overall survival.

  completion of study

• To evaluate pharmacodynamic changes in tumor vascular parameters (e.g blood flow, blood volume, time to peak in ROC -receiver operator characteristics curve) by DCE-MRI and correlate with outcomes.

  completion of study

• To evaluate biologic markers such as VEGF, eNOS and HIF1-alpha, VEGF-R2 genetic polymorphisms and serum proteomics, and correlate with outcomes.

  completion of study

• To evaluate resectability rates of tumors after treatment.

  completion of treatment

Study Arms (1)

Gemcitabine + Sorafenib & radiotherapy

EXPERIMENTAL

Induction: Gemcitabine with Sorafenib for 4 weeks (1 cycle). Chemo-radiotherapy: Gemcitabine with Sorafenib and Radiotherapy for 5 weeks. Sorafenib will be given in escalating dose cohorts. Sorafenib only: Sorafenib alone for 4 weeks. Consolidation: Gemcitabine with Sorafenib for 16 weeks (4 cycles). Maintenance: Sorafenib alone until disease progression.

Drug: Gemcitabine, Sorafenib; Procedure: Radiotherapy

Interventions

Gemcitabine, Sorafenib DRUG

Gemcitabine is given IV Sorafenib is given orally of varying doses: 1. Sorafenib 200 mg po qd ( during combination therapy) 2. Sorafenib 400 mg po qd ( during combination therapy) 3. Sorafenib 400 mg po bid ( during combination therapy)

Also known as: Gemzar ( gemcitabine), Sorafenib (BAY 43-9006)

Gemcitabine + Sorafenib & radiotherapy

Radiotherapy PROCEDURE

1.8 Gy CTV daily for 5 weeks

Gemcitabine + Sorafenib & radiotherapy

Eligibility Criteria

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

You may qualify if:

• Histologically/pathologically confirmed locally advanced unresectable or borderline unresectable pancreatic cancer \& no evidence of metastatic disease. Diagnosis of locally advanced unresectable pancreatic cancer is based on assessment by dual-phase CT scan and/or endoscopic ultrasound (EUS).
• Age ≥ 18 years at time of consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) \& obtained by dual-phase CT scan within 14 days prior to being registered for protocol therapy.
• Tumor size ≥ 2 cm on dual-phase computed tomography scan.
• Adequate organ function documented within 14 days of registration as laboratory tests per protocol.
• Patients with biliary obstruction must have percutaneous transhepatic drainage or endoscopic stent placement prior to starting study treatment
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Women of childbearing potential \& men must agree to use adequate contraception (barrier method of birth control) prior to study entry \& for the duration of study participation \& for at least three months after the last administration of sorafenib.
• Ability to understand \& the willingness to sign a written informed consent. A signed informed consent \& authorization for release of personal health information must be obtained prior to any study specific procedures.
• Patients with a history of malignancy are eligible provided they have been curatively treated \& demonstrate no evidence for recurrence of that cancer.

You may not qualify if:

• Prior treatment with Gemcitabine within 6 months prior to registration.
• Prior treatment with Sorafenib or other Ras or VEGF pathway inhibitors.
• Prior radiation therapy to the upper abdomen
• Evidence of metastatic disease
• Clinical evidence of duodenal mucosal invasion by tumor (as documented by endoscopy or endoscopic ultrasound).
• Minor surgical procedure (e.g. fine needle aspiration or needle biopsy) within 14 days of study registration.
• Major surgical procedure, significant traumatic injury, or serious non-healing wound, ulcer or bone fracture within 21 days of study registration; investigator has to document adequate healing has occurred prior to study registration.
• Any of the following within 6 months prior to study drug administration: severe/unstable angina (anginal symptoms at rest), new onset angina (began within the last 3 months) or myocardial infarction, congestive heart failure, cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• History of thrombotic or embolic events such as cerebrovascular accident or transient ischemic attack within the past 6 months. History of aneurysm or arteriovenous malformation.
• Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
• Active clinically serious infection \> Common Toxicity Criteria for Adverse Effects (CTCAE) grade 2.
• Receipt of any investigational agent within 4 weeks of study registration.
• Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management.
• Pulmonary hemorrhage/bleeding event \> CTCAE Grade 2 within 4 weeks of study registration
• Any other hemorrhage/bleeding event \> CTCAE Grade 3 within 4 weeks of study registration

Sponsors & Collaborators

• Indiana University School of Medicine: lead
• Amgen: collaborator

Study Sites (1)

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; Sorafenib; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Therapeutics

Study Officials

• Romnee Clark, MD

  IU Simon Cancer Center

  PRINCIPAL INVESTIGATOR

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: September 11, 2006
• First Posted: September 12, 2006
• Study Start: September 1, 2006
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2014
• Last Updated: February 29, 2016

Record last verified: 2016-02

Locations

US (1)