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NCT01431794

Gemcitabine + Nab-paclitaxel With LDE-225 (Hedgehog Inhibitor) as Neoadjuvant Therapy for Pancreatic Adenocarcinoma

Terminated Phase 1, PHASE2 Results posted Last updated 22 January 2020
What this trial tests

Phase 1, PHASE2 trial testing LDE225-600mg in Pancreatic Ductal Adenocarcinoma in 23 participants. Terminated before completion.

Timeline
27 December 2011
Primary endpoint
5 November 2018
5 November 2018

Quick facts

Lead sponsorSidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment23
Start date27 December 2011
Primary completion5 November 2018
Estimated completion5 November 2018
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins — full company profile →

Who can join

18 and older, any sex, with Pancreatic Ductal Adenocarcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phase I - Safety and Feasibility of Gemcitabine and Nab-Paclitaxel in Combination With LDE-225 as Neoadjuvant Therapy as Measured by Number of Participants Who Tolerated the Maximal Dose of LDE-225 Primary · 5 years

Number of participants who tolerated the maximal dose of LDE-225 in combination with gemcitabine, nab-paclitaxel as neoadjuvant therapy in patients with borderline resectable pancreatic adenocarcinoma (PDA).

GroupValue95% CI
Phase I: Gem, Nab-paclitaxel, and LDE225-600mg13
Phase I: Gem, Nab-paclitaxel, and LDE225-400mg0
Phase I: Gem, Nab-paclitaxel, and LDE225-800mg0
Overall Survival Secondary · 5 years

Number of months alive from cycle 1, Day 1 until 5 years post-intervention or death, whichever comes first.

GroupValue95% CI
Phase I: Gem, Nab-paclitaxel, and LDE225-600mg34.33.7 – 60
Overall Tumor Response as Determined by Number of Participants With Complete or Partial Response Secondary · 5 years

Number of participants who experienced complete response (CR) or partial response (PR), as defined by RECIST v1.0; where CR is a disappearance of all target lesions and PR is ≥30% reduction of target lesions.

GroupValue95% CI
Phase I: Gem, Nab-paclitaxel, and LDE225-600mg3

Adverse events — posted to ClinicalTrials.gov

Time frame: up to 3 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase I, Gem, Nab-paclitaxel, and LDE225-600mg
Serious: 8/13 (62%)
Deaths: 2/13
Phase I, Gem, Nab-paclitaxel, and LDE225-400mg
Serious: 0
Deaths: 0
Phase I, Gem, Nab-paclitaxel, and LDE225-800mg
Serious: 0
Deaths: 0
Phase II, Arm A: Gem, Nab-paclitaxel, and LDE 225
Serious: 0
Deaths: 0
Phase II, Arm B: Gemcitabine and Nab-paclitaxel
Serious: 0
Deaths: 0

Serious adverse events (9 terms)

ReactionSystemPhase I, Gem, Nab-paclitax…Phase I, Gem, Nab-paclitax…Phase I, Gem, Nab-paclitax…Phase II, Arm A: Gem, Nab-…Phase II, Arm B: Gemcitabi…
nausea, vomittingGeneral disorders—————
abdomina painGastrointestinal disorders—————
rhabdomyolysisMusculoskeletal and connective tissue disorders—————
fever and tachydysrhythmiaCardiac disorders—————
spesisInfections and infestations—————
obstructionGastrointestinal disorders—————
toxic mega-colonGastrointestinal disorders—————
pancreatitisGastrointestinal disorders—————
elevated creatine kinaseBlood and lymphatic system disorders—————
Other adverse events (20 terms — click to expand)

ReactionSystemPhase I, Gem, Nab-paclitax…Phase I, Gem, Nab-paclitax…Phase I, Gem, Nab-paclitax…Phase II, Arm A: Gem, Nab-…Phase II, Arm B: Gemcitabi…
WBC decreasedBlood and lymphatic system disorders—————
Hemoglobin decreasedBlood and lymphatic system disorders—————
ALT increasedHepatobiliary disorders—————
Glucose increasedMetabolism and nutrition disorders—————
Alkaline phosphatase increasedMetabolism and nutrition disorders—————
AST increasedHepatobiliary disorders—————
Calcium decreasedMetabolism and nutrition disorders—————
Lymphocytes decreasedBlood and lymphatic system disorders—————
Neutrophiles decreasedBlood and lymphatic system disorders—————
AnorexiaMetabolism and nutrition disorders—————
Weight lossGeneral disorders—————
NauseaGeneral disorders—————
sodium decreasedMetabolism and nutrition disorders—————
FatigueGeneral disorders—————
Albumin decreasedBlood and lymphatic system disorders—————
Platelets decreasedBlood and lymphatic system disorders—————
ConstipationGastrointestinal disorders—————
Abdomin painGastrointestinal disorders—————
Back painMusculoskeletal and connective tissue disorders—————
FeverGeneral disorders—————

Most-reported serious reactions: nausea, vomitting, abdomina pain, rhabdomyolysis, fever and tachydysrhythmia, spesis, obstruction, toxic mega-colon, pancreatitis.

Data from ClinicalTrials.gov NCT01431794 adverse events section.

Sponsor's own description

This is an open-label phase 1/2 study that will combine the chemotherapy agents gemcitabine and nab-paclitaxel with an oral hedgehog inhibitor LDE225 (Sonidegib). The objective is to assess tolerability and the resection rate of patients with borderline resectable pancreatic adenocarcinoma who use this treatment.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting cancer stem cell pathways for cancer therapy.
    Yang L, Shi P, Zhao G, Xu J, et al · · 2020 · cited 1354× · PMID 32296030 · DOI 10.1038/s41392-020-0110-5
  2. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update.
    Takebe N, Miele L, Harris PJ, Jeong W, et al · · 2015 · cited 1034× · PMID 25850553 · DOI 10.1038/nrclinonc.2015.61
  3. Targeting the Sonic Hedgehog Signaling Pathway: Review of Smoothened and GLI Inhibitors.
    Rimkus TK, Carpenter RL, Qasem S, Chan M, et al · · 2016 · cited 411× · PMID 26891329 · DOI 10.3390/cancers8020022
  4. Wound healing and cancer stem cells: inflammation as a driver of treatment resistance in breast cancer.
    Arnold KM, Opdenaker LM, Flynn D, Sims-Mourtada J. · · 2015 · cited 84× · PMID 25674014 · DOI 10.4137/cgm.s11286
  5. Safety and Tolerability of Sonic Hedgehog Pathway Inhibitors in Cancer.
    Carpenter RL, Ray H. · · 2019 · cited 77× · PMID 30649745 · DOI 10.1007/s40264-018-0777-5
  6. Hedgehog Signaling Pathway and Autophagy in Cancer.
    Zeng X, Ju D. · · 2018 · cited 76× · PMID 30081498 · DOI 10.3390/ijms19082279
  7. Nano albumin bound-paclitaxel in pancreatic cancer: Current evidences and future directions.
    Giordano G, Pancione M, Olivieri N, Parcesepe P, et al · · 2017 · cited 67× · PMID 28932079 · DOI 10.3748/wjg.v23.i32.5875
  8. Recent Advances in the Clinical Targeting of Hedgehog/GLI Signaling in Cancer.
    Xie H, Paradise BD, Ma WW, Fernandez-Zapico ME. · · 2019 · cited 61× · PMID 31035664 · DOI 10.3390/cells8050394

Verify or expand the search:

Other recruiting trials for Pancreatic Ductal Adenocarcinoma

Currently open trials in the same condition.

Other Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins trials

Trials by the same sponsor.

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