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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

Phase 1
18 Years
Open (Enrolling)
Pancreatic Carcinoma Non-resectable, Metastatic Pancreatic Cancer

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Trial Information

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

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.

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.

Type of Study:


Study Design:

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

Outcome Measure:

To determine the dose limiting toxicities

Outcome Time Frame:

weekly physician and nurse assessment and in between as needed

Safety Issue:


Principal Investigator

Steven Cohen, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fox Chase Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

September 2008

Completion Date:

December 2013

Related Keywords:

  • Pancreatic Carcinoma Non-resectable
  • Metastatic Pancreatic Cancer
  • pancreatic cancer
  • locally advanced
  • unresectable
  • metastatic pancreatic cancer
  • Carcinoma
  • Pancreatic Neoplasms



Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
Karmanos Cancer InstitueDetroit, Michigan  48201
Reading Medical CenterWest Reading, Pennsylvania  19611