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Phase 1/2 Safety and Feasibility of Gemcitabine in Combination With LDE-225 as Neoadjuvant Therapy in Patients With Borderline Resectable Pancreatic Adenocarcinoma


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Resectable Pancreatic Adenocarcinoma

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Trial Information

Phase 1/2 Safety and Feasibility of Gemcitabine in Combination With LDE-225 as Neoadjuvant Therapy in Patients With Borderline Resectable Pancreatic Adenocarcinoma


The investigators propose treating 6-12 patients during the phase 1 portion and 40 patients
in the phase 2 stage.

Phase 1 Stage:

1. Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8 and 15 in combination with escalating
doses of LDE-225. After completion of neoadjuvant therapy if the patients are eligible for
resection this will be performed followed by combined chemotherapy and radiation and two
additional cycles of Gemcitabine 1000 mg/m2 in combination with LDE-225.

Phase 2 Stage: In the Phase 2 stage the patients will be randomized to receive gemcitabine
with or without the hedgehog inhibitor LDE225:

1. Arm A: Four cycles of gemcitabine 1000 mg/m2 on days 1, 8 and 15 in combination with
LDE-225 at the recommended phase 2 dose.

2. Arm B: Four cycles of gemcitabine 1000 mg/m2 on days 1, 8 and 15.

After completion of neoadjuvant therapy if the patients are eligible for resection this will
be performed followed by combined chemotherapy and radiation and two additional cycles of
the pre-surgical therapy.

Several correlative laboratory studies will be conducted during the course of this study.
They were designed around the goals of providing us with a better understanding of how the
stroma-tumor interaction and the intra-tumoral drug levels of gemcitabine are affected with
the use of LDE-225. Two additional biopsies are required to participate in this study.


Inclusion Criteria:



.Histologically or cytologically confirmed adenocarcinoma of the pancreas.

- Must have borderline resectable pancreatic adenocarcinoma

- Measurable disease, defined as at least one lesion that can be accurately measured in
at least one dimension

- No previous radiotherapy, surgery, chemotherapy or investigational drug therapy.

- Age >18 years .Life expectancy of greater than 1 month.

- ECOG performance status 0 or 1

- Adequate organ and marrow function .Asymptomatic for jaundice and ascites. Pain
symptoms should be stable.

- Negative serum pregnancy test

- Sexually active males should agree to use a barrier form of contraception, even if
they have had a vasectomy, during the study and for 3 months after stopping LDE225.
.Agree not to donate blood products for 12 months after stopping LDE225. .Willing to
have two biopsies while on treatment for correlative studies.

Exclusion Criteria:

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to LDE225 or other agents used in the study.

- Patients taking medications with narrow therapeutic indices that are metabolized by
cytochrome P450 (CYP450), including warfarin sodium (Coumadin®)

- Uncontrolled illness including, but not limited to, ongoing or active infection
requiring IV antibiotics, symptomatic congestive heart failure not controlled with
medication, unstable angina pectoris, cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements.

- Pregnant women are excluded

- Patient has undergone a major surgery, other than diagnostic surgery within four
weeks prior to starting treatment on this study.

- Patients who are receiving treatment with medications known to be moderate and strong
inhibitors or inducers of CYP3A4/5 or drugs metabolized by CYP2B6 or CYP2C9 that have
narrow therapeutic index, and that cannot be discontinued before starting treatment
with LDE225. Medications that are strong CYP3A4/5 inhibitors should be discontinued
at least 7 days and strong CYP3A/5 inducers for at least 2 weeks prior to starting
treatment with LDE225.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Phase 1/2 Safety and Feasibility of Gemcitabine in combination with LDE-225 as Neoadjuvant Therapy in Patients with Borderline Resectable Pancreatic Adenocarcinoma.

Outcome Description:

Primary objective for phase I component of the trial: • To find the maximal tolerated dose of the combination of gemcitabine and LDE225 as neoadjuvant therapy in patients with borderline resectable pancreatic adenocarcinoma. Primary objective for phase II component of the trial: • To evaluate the resection rate of two preoperative chemotherapy regimens in patients with borderline resectable pancreatic adenocarcinoma.

Outcome Time Frame:

2 years

Safety Issue:

Yes

Principal Investigator

Ana De Jesus-Acosta, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center JHMI

Authority:

United States: Food and Drug Administration

Study ID:

J1130

NCT ID:

NCT01431794

Start Date:

September 2011

Completion Date:

Related Keywords:

  • Resectable Pancreatic Adenocarcinoma
  • Pancreatic ductal adenocarcinoma (PDA)Neoplasms
  • LDE225
  • neoadjuvant
  • cytotoxic
  • hedgehog (Hh) inhibitors
  • stromal cells
  • resectable PDA
  • Pancreatic Diseases
  • Carcinoma
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous

Name

Location
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410