RO4929097 Before Surgery in Treating Patients With Pancreatic Cancer

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01192763
First received: August 31, 2010
Last updated: September 27, 2013
Last verified: September 2013
  Purpose

This phase I trial is studying the side effects of RO4929097 before surgery in treating patients with pancreatic cancer. RO4929097 may stop the growth of tumor cells by blocking some enzymes needed for cell growth. Giving RO4929097 before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.


Condition Intervention Phase
Adenocarcinoma of the Pancreas
Stage IA Pancreatic Cancer
Stage IB Pancreatic Cancer
Stage IIA Pancreatic Cancer
Stage IIB Pancreatic Cancer
Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097
Other: laboratory biomarker analysis
Other: pharmacological study
Procedure: neoadjuvant therapy
Procedure: therapeutic conventional surgery
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Neoadjuvant Pharmacodynamic Study Of RO4929097 (RO) in Pancreas Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Notch activity (expression of Hes-1) [ Time Frame: Up to day 3 (of course 1) ] [ Designated as safety issue: No ]
    Summarized as a binary endpoint for both the RO4929097 population and the stage-matched controls by the proportion and 95% exact binomial confidence interval.

  • Frequency and severity of adverse events as measured by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Toxicity will be determined with a 95% exact binomial confidence interval.


Secondary Outcome Measures:
  • Proportion of cancer stem cells (CD44+, CD24+, ESA+ population of cells) self-renewal and tumorigenesis as measured by FACS [ Time Frame: Up to day 3 (of course 1) ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: August 2010
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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.
Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097
Given orally
Other Names:
  • R4733
  • RO4929097
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Procedure: neoadjuvant therapy Procedure: therapeutic conventional surgery

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 surgery

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

      • Tumors with severe unilateral or bilateral SMV/portal involvement impingement
      • 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 absorption
  • 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 following:

    • 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 requirements
  • 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 study

    • 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 hypokalemia
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01192763

Locations
United States, California
Tower Cancer Research Foundation
Beverly Hills, California, United States, 90211-1850
City of Hope Medical Center
Duarte, California, United States, 91010
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
Central Illinois Hematology Oncology Center
Springfield, Illinois, United States, 60702
United States, Indiana
Fort Wayne Medical Oncology and Hematology Inc - State Boulevard
Fort Wayne, Indiana, United States, 46845
Sponsors and Collaborators
Investigators
Principal Investigator: Edward Kim University of Chicago Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01192763     History of Changes
Other Study ID Numbers: NCI-2011-02523, NCI-2011-02523, CDR0000683470, 10-089-A, 8522, U01CA062505, N01CM00071
Study First Received: August 31, 2010
Last Updated: September 27, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on July 26, 2014