Study of Low-Dose Fractionated Radiotherapy in Patients With Locally Advanced Metastatic Pancreatic Cancer

January 24, 2017 updated by: Fox Chase Cancer Center

Phase I Study of Low-Dose Fractionated Radiotherapy as a Chemosensitizer for Gemcitabine and Erlotinib in Patients With Locally Advanced or Limited Metastatic Pancreatic Cancer

People with pancreatic cancer usually have a large amount of the cancer in the area of the pancreas and around it when they are diagnosed with it. Or their cancer has spread (metastasized)outside that area of the abdomen and is not able to be surgically removed (resected). For patients with metastatic disease, one standard treatment is the combination of gemcitabine and erlotinib. This combination has shown slightly longer survival compared to getting gemcitabine alone. For patients with localized but unresectable disease, the standard treatment remains controversial. Early studies showed that chemotherapy and radiation together was better than either one used alone. The greatest benefit of external beam radiotherapy may be after a period of full-dose chemotherapy alone, to help the rapid spread. A problem of beginning treatment with standard radiotherapy is that the doses of chemotherapy usually have to be reduced sometimes by half.

Studies have already shown that low dose radiotherapy (LDRT)is safe. This study will evaluate the safety of LDRT instead of standard doses with full dosing of gemcitabine and erlotinib in patients with locally advanced or limited metastatic pancreatic cancer. Patients will be enrolled in groups of 3 to 6 each with a slightly higher dose of LDRT and erlotinib.

For patients with locally advanced disease, this protocol also may help because most patients develop and die from spread to the liver and abdominal cavity.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Pancreatic cancer is nearly universally fatal, with approximately 38,000 new cases and 34,000 deaths expected in 2008.1 The majority of patients present with disease that is not amenable to curative resection. For patients with metastatic disease, one standard treatment is the combination of gemcitabine with the small molecule epidermal growth factor tyrosine kinase inhibitor erlotinib. This combination results in a modest survival benefit compared to single agent gemcitabine.2

For patients presenting with localized but unresectable disease, the standard treatment remains controversial. Early studies demonstrated that chemotherapy and radiation was superior to either modality alone.3 However, recent studies of systemic therapy alone have typically included a small but real minority of patients with locally advanced disease, supporting that systemic therapy alone is a reasonable treatment option.2 Adding to the confusion are recent European reports that systemic therapy alone may be superior to combined modality therapy, at least when used initially.4 The greatest benefit of external beam radiotherapy may be after a period of full-dose chemotherapy alone, to ensure that rapid metastases do not develop.5 A limitation of beginning treatment with conventional external beam radiotherapy is a requirement to reduce dosing of gemcitabine by 40-50%. Given the safety and preclinical rationale for LDRT, we propose this phase I study to evaluate the safety of LDRT with standard dosing of gemcitabine and erlotinib in patients with locally advanced or limited metastatic pancreatic cancer. Patients will be enrolled in cohorts with escalating doses of low dose radiotherapy. Radiation ports will be uniform between patients as described in Section 5.6 below. As LDRT is administered to sites of disease in liver and abdominal cavity to iliac crest, patients with metastatic disease confined to these areas will be eligible. For patients with locally advanced disease, this protocol also has high rationale, as the overwhelming majority of patients develop and succumb to recurrences in liver and abdominal cavity,10 areas which would be covered by the proposed radiation field. The dose of 2880 cGy is the limit because of kidney and other upper abdominal organ potential for toxicity.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institue
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • West Reading, Pennsylvania, United States, 19611
        • Reading Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients must have a diagnosis of adenocarcinoma of the pancreas that is not amenable to curative surgical resection. Patients with locally advanced unresectable disease and those patients with metastatic disease that can be encompassed in the radiation fields for this study (as assessed by treating radiation oncologist) are eligible.
  • Patients may not have received any prior chemotherapy for locally advanced or metastatic pancreatic cancer. Prior adjuvant chemotherapy completed >1 year previously is allowed.
  • Patients must be able to provide informed consent and HIPAA consent.
  • Patients must be ≥18 years of age

  • Adequate hematologic and organ function:

    • ANC ≥ 1,000/μL, platelets ≥ 100,000/μL, hemoglobin ≥ 9.0/dL
    • Bilirubin: ≤1.5X ULN
    • ALT/AST < 3.0 X upper limit of normal
    • Serum Creatinine: WNL
    • Albumin > 2.5 g/dL
  • Measurable and non-measurable disease are permitted
  • ECOG performance status 0-1
  • Patients must be able to swallow oral medications
  • Patients must be able to comply with study and follow up procedures

Exclusion Criteria:

  • No prior radiation therapy to the abdomen.
  • Patients must not have any other active illness (e.g. active/uncontrolled infection, uncontrolled cardiac disease, etc.) that would preclude safe therapy in the judgment of the treating physicians. Patients may be enrolled while still on antibiotics as long as clinical signs of active infection are absent.
  • Patients with concurrent active malignancy requiring therapy are not eligible. Patients with a history of malignancy within any timeframe not requiring ongoing therapy are eligible.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: radiotherapy and chemotherapy
gemcitabine will be administered at 1000mg/m2 IV on days 1 and 8 of each 21 day cycle. erlotinib at either 100mg (cohort 1-3) or 150mg (cohort 4) PO daily. Low dose fractionated radiotherapy (LDRT) will be given BID on days 1 and 2 and 8 and 9 of each 21 day cycle
Drug: gemcitabine
gemcitabine 1000mg/m2 days 1 and 8 of each 21 day cycle.
Other Names:
  • Gemzar
Drug: Erlotinib
Erlotinib 100mg or 150mg daily of each 21 day cycle
Other Names:
  • Tarceva
Radiation: low dose fractionated radiotherapy
low dose fractionated radiotherapy day 1 and 2, day 8 and 9 of each 21 day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To Determine the Dose Limiting Toxicities
Time Frame: weekly physician and nurse assessment and in between as needed until 30 days after treatment termination
weekly physician and nurse assessment and in between as needed until 30 days after treatment termination

Secondary Outcome Measures

Outcome Measure
Time Frame
To Measure Progression Free Survival and Overall Survival
Time Frame: Evaluate CT scans after every 2 cycles of therapy (about every 6 weeks) and long term follow up every 3 months once off treatment for survival
Evaluate CT scans after every 2 cycles of therapy (about every 6 weeks) and long term follow up every 3 months once off treatment for survival

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fox Chase Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

February 1, 2015

Study Registration Dates

First Submitted

September 26, 2008

First Submitted That Met QC Criteria

September 26, 2008

First Posted (Estimate)

September 29, 2008

Study Record Updates

Last Update Posted (Actual)

March 7, 2017

Last Update Submitted That Met QC Criteria

January 24, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FER-GI-021
  • OSI4485s (Other Identifier: Genentech)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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