Study of Low-Dose Fractionated Radiotherapy in Patients With Locally Advanced Metastatic Pancreatic Cancer
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|ClinicalTrials.gov Identifier: NCT00761345|
Recruitment Status : Completed
First Posted : September 29, 2008
Results First Posted : March 31, 2016
Last Update Posted : March 7, 2017
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|
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 (Clinical Trial)|
|Actual Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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
gemcitabine 1000mg/m2 days 1 and 8 of each 21 day cycle.
Other Name: GemzarDrug: Erlotinib
Erlotinib 100mg or 150mg daily of each 21 day cycle
Other Name: TarcevaRadiation: low dose fractionated radiotherapy
low dose fractionated radiotherapy day 1 and 2, day 8 and 9 of each 21 day cycle
- To Determine the Dose Limiting Toxicities [ Time Frame: weekly physician and nurse assessment and in between as needed until 30 days after treatment termination ]
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00761345
|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|
|Principal Investigator:||Steven Cohen, MD||Fox Chase Cancer Center|