Biomarker‐driven trial in metastatic pancreas cancer: feasibility in a multicenter study of saracatinib, an oral <scp>S</scp>rc inhibitor, in previously treated pancreatic cancer

Arcaroli, John J.; Quackenbush, Kevin S.; Dasari, Arvind; Powell, Rebecca W.; McManus, Martine C.; Tan, Aik Choon; Foster, Nathan R.; Picus, Joel; Wright, John J.; Nallapareddy, Sujatha; Erlichman, Charles; Hidalgo, Manuel; Messersmith, Wells A.

doi:10.1002/cam4.27

Cited by 14 publications

(4 citation statements)

References 37 publications

(42 reference statements)

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“…In a phase II clinical trial of saracatinib in patients previously treated for pancreatic cancer, saracatinib was administered orally and continuously in 28-day cycles. 68 As only two patients (11%) patients survived for at least 6 months, the study was amended as a biomarker-driven trial. However, of the 47 patients screened, only one patient was biomarker positive.…”

Section: Introductionmentioning

confidence: 99%

Current status and dilemma of second-line treatment in advanced pancreatic cancer: is there a silver lining?

Hua

Shi

Liang

et al. 2018

OTT

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Pancreatic cancer remains one of the most lethal malignant diseases worldwide. The majority of patients present with advanced disease and, therefore, need palliative chemotherapy. Some chemotherapeutic regimens have been well established as first-line therapies and have been shown to increase survival; however, almost all patients with advanced pancreatic cancer will experience disease progression after first-line therapy. Nevertheless, many patients who retain good performance status after initial treatment remain good candidates for additional therapy. Historically, few studies have assessed second-line therapy, with most reports representing small phase II trials with variable findings; however, clinical research for second-line treatment has increased in the past decade, and several randomized controlled trials using different regimens have been published. The current literature shows varying results on treatment efficacy and tolerability. Thus, we reviewed the published data on the use of chemotherapy in the second-line setting for the treatment of advanced pancreatic cancer.

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Section: Introductionmentioning

confidence: 99%

Current status and dilemma of second-line treatment in advanced pancreatic cancer: is there a silver lining?

Hua

Shi

Liang

et al. 2018

OTT

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“…As a means to demonstrate the feasibility and future use of the scoring system, Table 2 provides examples for how the scoring system can be applied, in this case by using therapeutic agents that have been recently evaluated in osteosarcoma patients. These agents include liposomal muramyl-tripeptide phosphatidyl-ethanolamine (L-MTP-PE) and inhaled granulocyte-colony stimulating factor (GM-CSF), (36-38). Based on supportive preclinical data and phase II trials in osteosarcoma, L-MTP-PE was advanced to a phase III trial in osteosarcoma.…”

Section: The Quagmire For Osteosarcoma Metastasis Drug Developmentmentioning

confidence: 99%

Toward a Drug Development Path That Targets Metastatic Progression in Osteosarcoma

Khanna

Fan

Görlick

et al. 2014

Clinical Cancer Research

129

132

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Despite successful primary tumor treatment, the development of pulmonary metastasis continues to be the most common cause of mortality in osteosarcoma patients. A conventional drug development path requiring drugs to induce regression of established lesions has not led to improvements for osteosarcoma patients in over 30 years. Based on our growing understanding of metastasis biology, it is now reasonable and essential that we focus on developing therapeutics that target metastatic progression. To advance this agenda a meeting of key opinion leaders and experts in the metastasis and osteosarcoma communities was convened in Bethesda Maryland. The goal of this meeting was to provide a “Perspective” that would establish a preclinical translational path that could support the early evaluation of potential therapeutic agents that uniquely target the metastatic phenotype. Although focused on osteosarcoma the need for this perspective is shared among many cancer types. The consensus achieved from the meeting included the following: That the biology of metastatic progression is associated with metastasis-specific targets/processes that may not influence grossly detectable lesions; targeting of metastasis-specific processes is feasible; rigorous preclinical data is needed to support translation of metastasis-specific agents into human trials where regression of measurable disease is not an expected outcome; preclinical data should include an understanding of mechanism of action, validation of pharmacodynamic markers of effective exposure and response, the use of several murine models of effectiveness, and where feasible the inclusion of the dog with naturally occurring osteosarcoma to define the activity of new drugs in the micro-metastatic disease setting.

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“…Some examples of novel drugs that failed to clearly augment efficacy when added to chemotherapy in single arm studies include curcumin 73, 74 , masitinib (multi-tyrosine kinase inhibitor eg c-kit, PDGFR, Lyn) 75 , Z-360 (gastrin inhibitor) 76 , bryostatin-1 (protein kinase C inhibitor) 77 , flavopiridol (pan-cyclin dependent kinase inhibitor) 78 , and saracatinib (Src inhibitor) 79 (Table 4). Saracatinib has also been studied as a single agent in previously treated patients 80 . After determining lack of efficacy in unselected patients, the authors modified the trial to select patients based on 2 biomarkers predictive of response to Src inhibition in patient-derived xenografts.…”

Section: Phase II Clinical Trials In Advanced Pancreatic Cancermentioning

confidence: 99%

Phase II clinical trials on investigational drugs for the treatment of pancreatic cancers

Kim¹,

Semrad²,

Bold³

2015

Expert Opinion on Investigational Drugs

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Introduction Despite some recent advances in treatment options, pancreatic cancer remains a devastating disease with poor outcomes. In a trend contrary to most malignancies, both incidence and mortality continue to rise due to pancreatic cancer. The majority of patients present with advanced disease and there are no treatment options for this stage that have demonstrated a median survival greater than 1 year. As the penultimate step prior to phase III studies involving hundreds of patients, phase II clinical trials provide an early opportunity to evaluate the efficacy of new treatments that are desperately needed for this disease. Areas Covered This review covers the results of published phase II clinical trials in advanced pancreatic adenocarcinoma published within the past 5 years. The treatment results are framed in the context of the current standards of care and the historic challenge of predicting phase III success from phase II trial results. Expert opinion Promising therapies remain elusive in pancreatic cancer based on recent phase II clinical trial results. Optimization and standardization of clinical trial design in the phase II setting, with consistent incorporation of biomarkers, is needed to more accurately identify promising therapies that warrant phase III evaluation.

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Biomarker‐driven trial in metastatic pancreas cancer: feasibility in a multicenter study of saracatinib, an oral Src inhibitor, in previously treated pancreatic cancer

Cited by 14 publications

References 37 publications

Current status and dilemma of second-line treatment in advanced pancreatic cancer: is there a silver lining?

Current status and dilemma of second-line treatment in advanced pancreatic cancer: is there a silver lining?

Toward a Drug Development Path That Targets Metastatic Progression in Osteosarcoma

Phase II clinical trials on investigational drugs for the treatment of pancreatic cancers

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