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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Fox Chase Cancer Center
ClinicalTrials.gov Identifier:
NCT00761345
First received: September 26, 2008
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Pancreatic Carcinoma Non-resectable
Metastatic Pancreatic Cancer
Drug: gemcitabine
Drug: Erlotinib
Radiation: low dose fractionated radiotherapy
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Fox Chase Cancer Center:

Primary Outcome Measures:
  • To determine the dose limiting toxicities [ Time Frame: weekly physician and nurse assessment and in between as needed ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: September 2008
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Gemzar
Drug: Erlotinib
Erlotinib 100mg or 150mg daily of each 21 day cycle
Other Name: Tarceva
Radiation: low dose fractionated radiotherapy
low dose fractionated radiotherapy day 1 and 2, day 8 and 9 of each 21 day cycle

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00761345

Locations
United States, Michigan
Karmanos Cancer Institue
Detroit, Michigan, United States, 48201
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
Reading Medical Center
West Reading, Pennsylvania, United States, 19611
Sponsors and Collaborators
Fox Chase Cancer Center
Investigators
Principal Investigator: Steven Cohen, MD Fox Chase Cancer Center
  More Information

No publications provided

Responsible Party: Fox Chase Cancer Center
ClinicalTrials.gov Identifier: NCT00761345     History of Changes
Other Study ID Numbers: FER-GI-021, OSI4485s
Study First Received: September 26, 2008
Last Updated: March 17, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Fox Chase Cancer Center:
pancreatic cancer
locally advanced
unresectable
metastatic pancreatic cancer

Additional relevant MeSH terms:
Carcinoma
Pancreatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Erlotinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014