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Adenocarcinoma of the PancreasPhase 1NCT01192763

RO4929097 Before Surgery in Treating Patients With Pancreatic Cancer

A Phase 1 study testing gamma-secretase/Notch signalling pathway inhibitor RO4929097, laboratory biomarker analysis and pharmacological study in people with Adenocarcinoma of the Pancreas and Stage IA Pancreatic Cancer, run by National Cancer Institute (NCI) at 6 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
gamma-secretase/Notch signalling pathway inhibitor RO4929097, laboratory biomarker analysis and pharmacological study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
6 sitesUnited States
Study dates
Aug 2010to Jan 2012
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 46Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Tower Cancer Research Foundation

    Beverly Hills, California, 90211-1850

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637-1470

  • City of Hope Medical Center

    Duarte, California, 91010

  • Fort Wayne Medical Oncology and Hematology Inc - State Boulevard

    Fort Wayne, Indiana, 46845

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • Central Illinois Hematology Oncology Center

    Springfield, Illinois, 60702

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
gamma-secretase/Notch signalling pathway inhibitor RO4929097, laboratory biomarker analysis, pharmacological study, neoadjuvant therapy, therapeutic conventional surgery
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01192763
Study groupRoleWhat they receive
Arm IExperimentalPatients 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.
Receives: Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097; Other: laboratory biomarker analysis; Other: pharmacological study; Procedure: neoadjuvant therapy; Procedure: therapeutic conventional surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Notch activity (expression of Hes-1)

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

    Measured: Up to day 3 (of course 1)

  2. Frequency and severity of adverse events as measured by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

    Toxicity will be determined with a 95% exact binomial confidence interval.

    Measured: Up to 1 year

Secondary outcomes (1)

  1. Proportion of cancer stem cells (CD44+, CD24+, ESA+ population of cells) self-renewal and tumorigenesis as measured by FACS

    Measured: Up to day 3 (of course 1)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Sep 2010 (estimated)
  2. Study startAug 2010
  3. Primary completionJan 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01192763
Sponsor's protocol ID
NCI-2011-02523
Other IDs
NCI-2011-02523, CDR0000683470, 10-089-A, 8522, U01CA062505, N01CM00071
Status last verified
Sep 2013
First submitted
31 Aug 2010
Last updated
30 Sep 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing gamma-secretase/Notch signalling pathway inhibitor RO4929097, laboratory biomarker analysis and pharmacological study in people with Adenocarcinoma of the Pancreas and Stage IA Pancreatic Cancer, run by National Cancer Institute (NCI) at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 46 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Notch activity (expression of Hes-1) (time frame: Up to day 3 (of course 1)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01192763.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2013.

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