Ignite Creation Date:
2024-05-05 @ 5:18 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00429858
Status:
TERMINATED
Last Update Posted:
2020-09-18
First Post:
2007-01-30
Brief Title:
Gemcitabine and S-1 for Locally Advanced Unresectable or Metastatic Pancreatic Cancer
Sponsor:
Andrew Ko
Organization:
University of California San Francisco
Study Overview
Official Title:
Individualized Management of Pancreatic Cancer With Targeted Therapeutics IMPACTT A Phase II Clinical Trial
Status:
TERMINATED
Status Verified Date:
2020-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Study accrual rate is very slow it was mandated by NCI to be terminated
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE Studying samples of tumor tissue and blood from patients with cancer in the laboratory may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer It may also help doctors predict a patients response to treatment and help plan the best treatment
PURPOSE This phase II trial is studying gene expression in predicting treatment response in patients receiving gemcitabine and S-1 for locally advanced unresectable or metastatic pancreatic cancer
PURPOSE This phase II trial is studying gene expression in predicting treatment response in patients receiving gemcitabine and S-1 for locally advanced unresectable or metastatic pancreatic cancer
Detailed Description:
OBJECTIVES
Primary
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
Secondary
Correlate intratumoral expression levels of other genes eg 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 ie biomarker response with each successive line of treatment
Tertiary
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 transporters
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 toxicity
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
Primary
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
Secondary
Correlate intratumoral expression levels of other genes eg 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 ie biomarker response with each successive line of treatment
Tertiary
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 transporters
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 toxicity
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| UCSF-H12191-29556-01 | OTHER | UCSF California CHR Approval | None |
| NCI-2011-01215 | REGISTRY | None | None |