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Pancreatic CancerPhase 1NCT00375310

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

A Phase 1 study testing Gemcitabine, Sorafenib and Radiotherapy in people with Pancreatic Cancer and Adenocarcinoma of the Pancreas, run by Indiana University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Gemcitabine, Sorafenib and Radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteUnited States
Study dates
Sep 2006to Nov 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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
  • Evidence or history of bleeding diathesis or coagulopathy.
  • Chronic, daily treatment with aspirin or other nonsteroidal anti-inflammatory medications.
  • Use of St. John's Wort, rifampin (rifampicin), ketoconazole, itraconazole, ritonavir or grapefruit juice.
  • Known or suspected allergy to Sorafenib or any agent given in the course of this trial.
  • Any condition that impairs patient's ability to swallow whole pills.
  • Any malabsorption problem.
  • Other severe, acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results \& in the judgment of the investigator would make the patient inappropriate for entry into this study.
  • History of collagen vascular disease.
  • Any contraindication to undergo magnetic resonance imaging

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Indiana University Simon Cancer Center

    Indianapolis, Indiana, 46202

Other trials in United States

About this study

Official title: Phase I Study of Gemcitabine With Novel RAF Kinase-Vascular Endothelial Growth Factor Receptor Inhibitor Sorafenib (BAY 43-9006) and Radiotherapy in Patients With Locally Advanced Unresectable Pancreatic Adenocarcinoma

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.

Read the detailed description

Pancreatic cancer treatment is hampered by its resistance to both chemo and radiotherapy. Gemcitabine-based chemoradiotherapy has become one of the standard therapies for localized unresectable pancreatic cancer, but with poor responses and survival rates of less than 12 months. Radiotherapy increases VEGF expression and activates the Ras/MEK/ERK pathway which may contribute to radioresistance, thus the addition of anti-angiogenic agents and/or Ras/ERK inhibitors could enhance radiation mediated cytotoxicity. Sorafenib is a novel dual-action Raf kinase and vascular endothelial growth factor receptors (VEGF-R2 and VEGF-R3) inhibitor targeting both angiogenic and Ras-Raf-1 signal transduction pathways. Based upon preliminary laboratory and clinical data Sorafenib holds promise for improving outcomes of therapy for patients with locally advanced unresectable pancreatic cancer.

Polymorphisms in genes involved in the angiogenesis pathway (VEGF, VEGF-R2, HIF-1 and eNOS) may contribute to the process of angiogenesis, tumor behavior, and may explain the heterogeneity in efficacy (and toxicity) of agents whose major mechanism of action is blocking angiogenesis33-37. Proteomic analysis may also contribute to identify patterns of response or resistance to therapies, and potentially predict outcomes.

Dynamic contrast enhanced (DCE)-MRI has been shown to be a useful pharmacodynamic marker of biological activity for anti-angiogenic agents38-40 and may also predict radiation therapy-induced vascular changes41. In vivo imaging of angiogenesis using DCE-MRI and the analysis of angiogenesis markers genetic polymorphisms may predict response and clinical benefit to therapy for unresectable pancreatic cancer patients. These biologic and pharmacodynamic endpoints will be analysed to correlate with the tumor activity seen.

Being tested
Gemcitabine, Sorafenib, Radiotherapy
Keywords
Phase I, Pancreas Cancer, Chemo-radiotherapy
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Gemcitabine, SorafenibDrug

    Also called Gemzar ( gemcitabine), Sorafenib (BAY 43-9006)

    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)

  • RadiotherapyProcedure or surgery

    1.8 Gy CTV daily for 5 weeks

Study groups in NCT00375310
Study groupRoleWhat they receive
Gemcitabine + Sorafenib & radiotherapyExperimentalInduction: 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.
Receives: Drug: Gemcitabine, Sorafenib; Procedure: Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: completion of study

Secondary outcomes (6)

  1. 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

    Measured: completion of study

  2. To evaluate time to disease progression and overall survival.

    Measured: completion of study

  3. 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.

    Measured: completion of study

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

    Measured: completion of study

  5. To evaluate resectability rates of tumors after treatment.

    Measured: completion of treatment

  6. To evaluate the maximum tolerated dose (MTD) for Sorafenib during Chemo-radiation.

    Measured: completion of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Sep 2006 (estimated)
  2. Study startSep 2006
  3. Primary completionNov 2010
  4. Study completionNov 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00375310
Sponsor's protocol ID
0607-09; IUCRO-0155
Status last verified
Feb 2016
First submitted
11 Sep 2006
Last updated
29 Feb 2016
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Gemcitabine, Sorafenib and Radiotherapy in people with Pancreatic Cancer and Adenocarcinoma of the Pancreas, run by Indiana University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To evaluate the safety and tolerability of the combined treatment with Gemcitabine with Sorafenib and radiotherapy in patients with localized unresectable pancreatic cancer. (time frame: completion of study). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00375310.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Feb 2016.

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