Individualized Management of Pancreatic Cancer With Targeted Therapeutics (IMPACTT): A Phase II Clinical Trial
- Correlate intratumoral expression level of ribonucleotide reductase subunit 1 (RRM1)
with response to gemcitabine hydrochloride therapy in patients with locally advanced
unresectable or metastatic adenocarcinoma of the pancreas.
- Correlate intratumoral expression levels of other genes (e.g., deoxycytidine kinase
[dCK], equilibrative nucleoside transporter 1 [ENT1], and concentrative nucleoside
transporters 1 and 3 [CNT1 and CNT3]) with response in these patients.
- Determine, preliminarily, the median survival of these patients, using a therapeutic
strategy entailing sequential addition of agents and decision making based on early CA
19-9 biomarker response.
- Determine the safety of this approach.
- Determine the percentage of patients classified as potential biomarker responders.
- Determine the time to progression with each successive line of treatment.
- Determine the proportion of patients with ≥ 25% decline in CA 19-9 biomarker (i.e.,
biomarker response) with each successive line of treatment.
- Identify other genes that may mediate sensitivity to gemcitabine hydrochloride, S-1,
and other agents with activity in pancreatic cancer.
- Determine the frequency of host genetic polymorphisms in various nucleoside
OUTLINE: This is a multicenter.
- Initial treatment (gemcitabine hydrochloride alone): Patients receive gemcitabine
hydrochloride IV over 100 minutes on days 1, 8, and 15. CA 19-9 levels are assessed in
weeks 1 and 3 of each course. Patients who are biomarker responders continue to receive
treatment with gemcitabine hydrochloride alone. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity. Patients who are no longer
biomarker responders or show other evidence of disease progression proceed to therapy
comprised of gemcitabine hydrochloride and S1.
- Gemcitabine hydrochloride and S-1 treatment: Patients receive gemcitabine hydrochloride
IV over 100 minutes on days 1 and 15 and oral S-1 twice daily on days 1-7 and 15-21.
Courses repeat every 28 days in the absence of disease progression or unacceptable
Patients undergo core needle tumor biopsy and fine-needle aspiration at baseline. Tissue
samples are analyzed for correlation between transcript and protein expression by
immunohistochemistry and for expression of genes and gene products that may mediate
sensitivity to gemcitabine hydrochloride (RRM1, ENT1, CNT1 and 3, dCK); S-1, thymidine
phosphorylase [TP], TS, DPD, and ORPT; and other anticancer treatments (ERCC-1, epidermal
growth factor receptor, GSK-3β) by reverse-transcriptase polymerase chain reaction. Tissue
samples are also analyzed by microarray and comparative genomic hybridization to identify
new genes that may predict chemotherapeutic response or mediate sensitivity to anticancer
therapy. Mutational status of KRAS and p53 gene are also assessed.
Blood samples are collected at baseline and are analyzed by genotyping assays to identify
polymorphic variants of select genes.
After completion of study treatment, patients are followed monthly.
PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• To correlate intratumoral expression level of ribonucleotide reductase subunit 1 (RRM1) with response to gemcitabine in patients with advanced pancreatic cancer.
2 years after the last patient is enrolled
Andrew Ko, MD
University of California, San Francisco
United States: Federal Government
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|