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

• ClinicalTrials.gov Identifier: NCT00761345
• Recruitment Status: Completed
• First Posted: September 29, 2008
• Results First Posted: March 31, 2016
• Last Update Posted: March 7, 2017
• Sponsor: Fox Chase Cancer Center
• Information provided by (Responsible Party): Fox Chase Cancer Center

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Pancreatic Carcinoma Non-resectable; Metastatic Pancreatic Cancer	Drug: gemcitabine; Drug: Erlotinib; Radiation: low dose fractionated radiotherapy	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: September 2008
• Actual Primary Completion Date: July 2014
• Actual Study Completion Date: February 2015

Arms and Interventions

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 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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

• Responsible Party: Fox Chase Cancer Center
• ClinicalTrials.gov Identifier: NCT00761345
• Other Study ID Numbers: FER-GI-021; OSI4485s ( Other Identifier: Genentech )
• First Posted: September 29, 2008
• Results First Posted: March 31, 2016
• Last Update Posted: March 7, 2017
• Last Verified: January 2017

Keywords provided by Fox Chase Cancer Center:

pancreatic cancer; locally advanced; unresectable; metastatic pancreatic cancer

Additional relevant MeSH terms:

Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Gemcitabine; Erlotinib Hydrochloride; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Protein Kinase Inhibitors