Abstract | AIM: PATIENTS AND METHODS: Eligibility criteria included locally advanced or metastatic pancreatic adenocarcinoma and no prior chemotherapy. In phase I saracatinib was escalated in combination with gemcitabine (1000 mg/m(2)) to determine the recommended phase II dose (RP2D). The study was then expanded to a single arm phase II trial using a Simon 2-stage design. The primary endpoint was objective tumor response (OR) plus stable disease ≥ 4 months (SD4) rate; if ≥ 8 patients had OR+SD4, the study would proceed to stage 2. RESULTS: Thirteen patients were enrolled into the phase I portion of this study. Saracatinib 175 mg PO daily was chosen as the RP2D in combination with gemcitabine. Twenty-one additional patients were then enrolled at the RP2D (phase II). Of the 22 response evaluable patients treated at the RP2D, 9 patients (40.9%) had progressive disease, 6 patients (27.3%) had stable disease for less than 4 months, 5 patients (22.7%) had SD4, and 2 patients (9.1%) had a partial response to treatment. Objective criteria for continuing to stage 2 were thus not met and the trial was closed following the accrual of 34 patients. CONCLUSION:
Saracatinib 175 mg daily in combination with gemcitabine is well tolerated but the combination did not improve efficacy over what would be expected from gemcitabine alone.
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Authors | Daniel J Renouf, Malcolm J Moore, David Hedley, Sharlene Gill, Derek Jonker, Eric Chen, David Walde, Rakesh Goel, Bernadette Southwood, Isabelle Gauthier, Wendy Walsh, Lynn McIntosh, Lesley Seymour |
Journal | Investigational new drugs
(Invest New Drugs)
Vol. 30
Issue 2
Pg. 779-86
(Apr 2012)
ISSN: 1573-0646 [Electronic] United States |
PMID | 21170669
(Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antimetabolites, Antineoplastic
- Benzodioxoles
- Protein Kinase Inhibitors
- Quinazolines
- Deoxycytidine
- saracatinib
- src-Family Kinases
- Gemcitabine
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Topics |
- Administration, Oral
- Aged
- Antimetabolites, Antineoplastic
(administration & dosage)
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, pharmacokinetics, therapeutic use)
- Benzodioxoles
(administration & dosage)
- Canada
- Deoxycytidine
(administration & dosage, analogs & derivatives)
- Disease Progression
- Drug Administration Schedule
- Female
- Humans
- Infusions, Intravenous
- Kaplan-Meier Estimate
- Male
- Middle Aged
- Pancreatic Neoplasms
(drug therapy, enzymology, pathology)
- Protein Kinase Inhibitors
(administration & dosage)
- Quinazolines
(administration & dosage)
- Treatment Outcome
- Tumor Burden
(drug effects)
- src-Family Kinases
(antagonists & inhibitors, metabolism)
- Gemcitabine
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