Evidence map›Paper›PMID 26715573›Full record

ArticleInvestigational new drugs2016

Phase I trial of vandetanib in combination with gemcitabine and capecitabine in patients with advanced solid tumors with an expanded cohort in pancreatic and biliary cancers.

Elizabeth R Kessler, S Gail Eckhardt, Todd M Pitts, Erica L Bradshaw-Pierce, Cindy L O'byrant, Wells A Messersmith, Sujatha Nallapreddy, Colin Weekes, Jennifer Spratlin, Christopher H Lieu and 4 more

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Investigational new drugs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00551096 (A Phase I Study of Gemcitabine, Capecitabine and ZD6474), which is not on this map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.9field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00551096 phase1completednot on this map

A Phase I Study of Gemcitabine, Capecitabine and ZD6474 (ZACTIMA) in Patients With Advanced Solid Tumors With an Expanded Cohort of Patients With Biliary or Pancreatic Malignancies.

TypeinterventionalSponsorUniversity of Colorado, DenverRan2007 to 2013Enrolled23ConditionsMalignant Solid Tumour, Biliary Cancer, Pancreatic CancerArmsGemcitabine, Capecitabine, ZD6474
3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
  2. Review
  3. Combination Therapies for Advanced Biliary Tract Cancer.Journal of clinical and translational hepatology · 2023
    Review
  4. Recent advances in targeted therapy for pancreatic adenocarcinoma.World journal of gastrointestinal oncology · 2023
    Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Targeting Angiogenesis in Biliary Tract Cancers: An Open Option.International journal of molecular sciences · 2017
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

Elizabeth R KesslerDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, MS 8117, 12801 E 17th Avenue, Room 8120, Aurora, CO, 80045, USA.
S Gail EckhardtDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, MS 8117, 12801 E 17th Avenue, Room 8120, Aurora, CO, 80045, USA.
Todd M PittsDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, MS 8117, 12801 E 17th Avenue, Room 8120, Aurora, CO, 80045, USA.
Erica L Bradshaw-PierceUniversity of Colorado Cancer Center, Aurora, Colorado, USA.
Cindy L O'byrantDepartment of Clinical Pharmacy, Skaggs School of Pharmacy, Aurora, CO, USA.
Wells A MessersmithDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, MS 8117, 12801 E 17th Avenue, Room 8120, Aurora, CO, 80045, USA.
Sujatha NallapreddyDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, MS 8117, 12801 E 17th Avenue, Room 8120, Aurora, CO, 80045, USA.
Colin WeekesDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, MS 8117, 12801 E 17th Avenue, Room 8120, Aurora, CO, 80045, USA.
Jennifer SpratlinDepartment of Oncology, University of Alberta, Edmonton, AB, Canada.
Christopher H LieuDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, MS 8117, 12801 E 17th Avenue, Room 8120, Aurora, CO, 80045, USA.
Madeleine A KaneDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, MS 8117, 12801 E 17th Avenue, Room 8120, Aurora, CO, 80045, USA.
Sarah EppersUniversity of Colorado Cancer Center, Aurora, Colorado, USA.
Elizabeth FreasUniversity of Colorado Cancer Center, Aurora, Colorado, USA.
Stephen LeongDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, MS 8117, 12801 E 17th Avenue, Room 8120, Aurora, CO, 80045, USA. stephen.leong@ucdenver.edu.
University of Colorado Cancer Center · USUniversity of Colorado Denver · USUniversity of Montana · USUniversity of Alberta · CA

Funding

Paul Calabresis Award in Clinical Oncology ResearchK12CA086913 · NCI · UNIVERSITY OF COLORADO DENVER · PI VIRGINIA F. BORGES, Jill E Slansky · 2000 to 2026
$17.8M
NCI NIH HHS K12 CA086913NCI NIH HHS K12CA086913-10
6 · The paper itself

Abstract

backgroundVandetanib is a multitargeted tyrosine kinase inhibitor that affects vascular endothelial growth factor receptor (VEGF), epidermal growth factor (EGF), and rearranged during transfection (RET) mediated receptors which are important for growth and invasion of biliary and pancreatic cancers. This phase I study evaluated the safety profile of vandetanib in combination with standard doses of gemcitabine and capecitabine in order to determine the maximum tolerated dose (MTD).

methodsIn this single center phase I trial, patients received gemcitabine intravenously (i.v.) at 1000 mg/m2 days 1, 8, 15 in a 28 day cycle, capecitabine orally at 850 mg/m2 twice daily on days 1-21, and escalating doses of vandetanib (200 or 300 mg orally daily). Once the MTD was defined, an expansion cohort of patients with advanced biliary cancers and locally advanced or metastatic pancreatic cancer was enrolled. Blood samples were also collected at predetermined time points for biomarker analysis.

resultsTwenty-three patients were enrolled: 9 in the dose escalation and 14 in the dose expansion cohort. One dose limiting toxicity (DLT), of grade 4 neutropenia, occurred in the 200 mg vandetanib cohort. The most common adverse effects were diarrhea (39 %), nausea and vomiting (34%), and rash (33%). There were 3 partial responses and stable disease of >2 months (range 2-45, median 5) was observed in 15/23 patients. There was no association between changes in biomarker analytes and disease response.

conclusionThe combination of gemcitabine, capecitabine and vandetanib is well tolerated at the recommended phase II dose of gemcitabine 1000 mg/m2 weekly for three consecutive weeks, capecitabine 850 mg/m2 BID days 1-21, and vandetanib 300 mg daily, every 28 days. This combination demonstrated promising activity in pancreaticobiliary cancers and further evaluation is warranted in these diseases. NCT00551096.

Indexed as

AdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiliary Tract NeoplasmsCapecitabineCohort StudiesDeoxycytidineFemaleGemcitabineHumansMaleMiddle AgedNeoplasm StagingPancreatic NeoplasmsPiperidinesQuinazolinesCapecitabineDeoxycytidineGemcitabinePiperidinesQuinazolinesvandetanibCholangiocarcinomaEGFPancreatic cancerPhase IRETVandetanibVEGF

Identifiers

PMID26715573
PMCPMC4788525
OpenAlexW2205041904

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.