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A Neoadjuvant Pharmacodynamic Study Of RO4929097 (RO) in Pancreas Cancer

Phase 1
18 Years
Open (Enrolling)
Adenocarcinoma of the Pancreas, Stage IA Pancreatic Cancer, Stage IB Pancreatic Cancer, Stage IIA Pancreatic Cancer, Stage IIB Pancreatic Cancer

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Trial Information

A Neoadjuvant Pharmacodynamic Study Of RO4929097 (RO) in Pancreas Cancer


I. To evaluate the effects of neoadjuvant gamma-secretase inhibitor RO4929097 on Notch
inhibition via interrogation of Hes-1 expression in patients with pancreatic cancer.


I. To evaluate the effects of this regimen on pancreatic cancer stem cell self-renewal and
tumorigenesis as compared to pancreatic stem cells from controls (patients who do not
receive treatment).

II. To evaluate the safety of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral gamma-secretase inhibitor RO4929097 on days 1-3 and 8-10 in the
absence of disease progression or unacceptable toxicity. Beginning 7 days after completion
of gamma-secretase inhibitor RO4929097, patients undergo complete resection comprising
pancreaticoduodenectomy, distal pancreatectomy, or total pancreatectomy based on the
anatomic location of the cancer. Tumor tissue from biopsy and surgery and blood samples are
collected periodically for pharmacodynamic studies.

After completion of study therapy, patients are followed up every 6 months for 1 year.

Inclusion Criteria:

- Histologically or cytologically confirmed pancreatic adenocarcinoma

- T1-3, N0-1, and M0 disease

- Surgically resectable disease confirmed by a surgeon experienced in pancreatic

- No borderline resectable disease defined as any of the following:

- Tumors with severe unilateral or bilateral SMV/portal involvement

- Abutment (or) encasement of hepatic artery

- SMA or celiac encasement (or) presence of SMV occlusion by tumor

- No metastatic disease

- ECOG performance status 0-1

- Life expectancy > 6 months

- WBC ≥ 3,000/mm³

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9 g/dL

- Total bilirubin ≤ 2 mg/dL

- AST and ALT ≤ 2.5 times upper limit of normal

- Creatinine ≤ 2 mg/dL

- Calcium, magnesium, phosphorous, and potassium normal

- Negative pregnancy test

- Not pregnant or nursing

- Fertile patients must use effective barrier-method contraception 4 weeks before,
during, and for ≥ 12 months after completion of treatment

- Able to swallow tablets

- No malabsorption syndrome or other condition that would interfere with intestinal

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to gamma-secretase inhibitor RO4929097 or other agents used in
the study

- No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or
hypokalemia despite adequate electrolyte supplementation

- Grade 1 hyponatremia with sodium ≤ 131 mg/dL is permissible

- No uncontrolled intercurrent illness including, but not limited to, any of the

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia other than chronic

- Stable atrial fibrillation

- Psychiatric illness/social situations that would limit compliance with study

- No baseline QTcF > 450 msec (male) or QTcF > 470 msec (female)

- Patients with a prior cancer with evidence of active cancer are excluded from this

- Patients with a prior cancer are permitted to enter this study as long as there
is no documented evidence of active malignancy

- No uncontrolled electrolyte abnormalities including hypocalcemia, hypomagnesemia, and

- No symptomatic congestive heart failure, unstable angina pectoris, and a history of
torsades de pointes or other significant cardiac arrhythmias

- No requirement for antiarrhythmics or other medications known to prolong QTc

- No other concurrent anticancer agents or therapies

- Recovered to < grade 2 toxicity related to prior therapy

- No prior chemotherapy or radiotherapy for pancreatic cancer

- No other concurrent investigational agents

- No concurrent medications with narrow therapeutic indices that are metabolized by
cytochrome P450 (CYP450), including warfarin sodium (Coumadin®), ketoconazole, or
grapefruit juice

- No concurrent strong inducers or inhibitors of CYP3A4

- No concurrent combination antiretroviral therapy for HIV-positive patients

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Notch activity (expression of Hes-1)

Outcome Description:

Summarized as a binary endpoint for both the RO4929097 population and the stage-matched controls by the proportion and 95% exact binomial confidence interval.

Outcome Time Frame:

Up to day 3 (of course 1)

Safety Issue:


Principal Investigator

Edward Kim

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

August 2010

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Pancreas
  • Stage IA Pancreatic Cancer
  • Stage IB Pancreatic Cancer
  • Stage IIA Pancreatic Cancer
  • Stage IIB Pancreatic Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Pancreatic Neoplasms



Central Illinois Hematology Oncology CenterSpringfield, Illinois  62701
City of Hope Medical CenterDuarte, California  91010
Tower Cancer Research FoundationBeverly Hills, California  90211
Illinois CancerCare-PeoriaPeoria, Illinois  61615
Fort Wayne Medical Oncology and Hematology Inc - State BoulevardFort Wayne, Indiana  46845