A Pilot Study of a Hedgehog Pathway Inhibitor (LDE-225) in Surgically Resectable Pancreas Cancer

NCT01694589 | Withdrawn Early Phase 1

• 3 other identifiers: 0711080220120066P30CA072720
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

We hypothesize that administration of LDE-225 in humans with pancreatic cancer will result in inhibition of paracrine HH signaling in the pancreatic tumor stroma while having no effect on autocrine signaling in the tumor cell compartment. Furthermore we hypothesize that treatment with LDE-225 will result in changes in the tumor stroma (decreased desmoplasia, increased vascularity) that will result in improved tumor blood flow. The purpose of this study is to determine if, where and how LDE-225 works in pancreatic cancer. A cancer cell's growth can depend on the cells and tissue around it. The cells and tissue make chemical signals to influence the cancer's growth. This research study is evaluating LDE-225 designed to interfere with one of the growth signals causing pancreatic cancer growth.

Conditions

Resectable Pancreatic Cancer

Keywords

pancreatic cancer; resectable pancreatic cancer

Outcome Measures

Primary Outcomes (1)

• Changes in mean Gli-1 levels before and after drug

  Means and variances of the (transformed) data for samples from stroma and tumor are calculated. Data is collected from patients in pairs (with the first observation from the biopsy prior to drug and the second after surgery, and after the drug), and it is expected these two observations will be correlated. Detectable differences for a range of four correlations will be computed.

  2 years

Secondary Outcomes (1)

• Complications from surgery by time of hospital discharge up to 30 days post-operatively

  2 years

Study Arms (1)

LDE-225

EXPERIMENTAL

LDE-225: dose - 800 mg, taken by mouth once daily for 2 weeks.

Drug: LDE-225

Interventions

LDE-225 DRUG

LDE-225 capsules will be administered as a fixed dose of 800 mg daily for two weeks.

Also known as: NVP-LDE225, Erismodegib

LDE-225

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with biopsy probable, resectable pancreatic cancer. Patients will be expected to undergo surgery a minimum of 14 days following signing consent.
• Patients must give informed consent.
• Patients must be over 18 and have an ECOG performance status ≤2 and life expectancy \> 3 months.
• Patients must have normal organ and marrow function as defined below:
• ANC ≥1,500 /µL
• Platelets ≥100,000 /µL
• Hemoglobin\>10gm/dl
• creatinine \<1.5 X ULN
• Plasma creatine phosphokinase (CK) \< 1.5 x ULN
• PT/PTT WNL
• Patients may have abnormal bilirubin, which is concluded by the surgeon to be related to biliary ductal obstruction, may be included if bilirubin \< 3 X ULN.
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \< 2.5 x upper limit of normal (ULN).

You may not qualify if:

• Poor surgical risk due to comorbidities or poor performance status
• Patients who have received prior treatment with a smoothened antagonist, (GDC-0449 (Genentech), IPI-926 (Infinity).
• Patients who have received chemotherapy within a period of time that is \< the cycle length used for that treatment (e.g. \<6 weeks for nitrosoureas, mitomycin-C) prior to starting study drug or who have not recovered from the side effects of such therapy
• Patients who have received wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
• Patients who have received biologic therapy (e.g. antibodies) ≤ 4 weeks prior to starting study drug or who have not recovered from the side effects of such therapy
• Patients who have been treated with a targeted agent ≤ 5 t1/2 or ≤ 4 weeks (whichever is shorter) prior to starting study drug or who have not recovered from the side effects of such therapy
• Patients who have received any other investigational agents ≤ 5 t1/2 or ≤ 4 weeks (whichever is shorter) prior to starting study drug or who have not recovered from the side effects of such therapy
• Poor oral intake and/or inability to take capsules
• Impairment of gastrointestinal function or gastrointestinal disease such as Chron's Disease or Ulcerative Cholitis, short-gut syndrome, celiac sprue disease that may significantly alter the absorption of LDE225
• Urgent/emergent need for surgery (\< 7 days)
• Documented cirrhotic liver disease, ongoing alcohol abuse, or known active or acute hepatitis
• Impaired cardiac function or clinically significant heart disease, including any one of the following:
• Angina pectoris within 3 months
• Acute myocardial infarction within 3 months
• QTcF \> 450 msec for males and \> 470 msec for females on the screening ECG

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• Rutgers Cancer Institute of New Jersey: collaborator
• National Cancer Institute (NCI): collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

sonidegib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Darren Carpizo, MD, PhD

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2012
• First Posted: September 27, 2012
• Study Start: November 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: July 1, 2014
• Last Updated: December 12, 2014

Record last verified: 2014-12

Locations

US (1)