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Adenocarcinoma of the PancreasPhase 2NCT01232829

Gamma Secretase Inhibitor RO4929097 in Previously Treated Metastatic Pancreas Cancer

A Phase 2 study testing gamma-secretase/Notch signalling pathway inhibitor RO4929097 in people with Adenocarcinoma of the Pancreas and Recurrent Pancreatic Cancer, run by National Cancer Institute (NCI) at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial is studying how well RO4929097 (gamma-secretase/Notch signalling pathway inhibitor RO4929097) works in treating patients with previously treated metastatic 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
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
3 sitesUnited States
Study dates
Oct 2010to May 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 metastatic pancreatic adenocarcinoma
  • Not amenable to potentially curative surgical resection
  • At least 1 prior regimen of chemotherapy, preferably gemcitabine-based, for metastatic disease
  • Evidence of disease progression
  • Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan
  • Available archived tumor tissue (baseline core biopsies or surgical tumor blocks)
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  • No diagnosis by fine-needle aspiration only
  • No known brain metastases
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (Karnofsky 70-100%)
  • White blood cell count (WBC) ≥ 3,000/mm³
  • Absolute neutrophil count (ANC) ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9 g/dL
  • Total bilirubin normal
  • Aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases present)
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Willingness to undergo 2 tumor biopsies, if required
  • Fertile patients must use 2 forms of contraception (i.e., barrier contraception and one other method of contraception) ≥ 4 weeks prior to, during, and for ≥ 12 months after completion of therapy
  • Negative pregnancy test
  • Not pregnant or nursing
  • Able to swallow pills
  • No patients with 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
  • Not serologically positive for hepatitis A, B, or C
  • No history of liver disease, other forms of hepatitis, or cirrhosis
  • No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia despite adequate electrolyte supplementation
  • 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)
  • No other malignancy within the past 5 years except curatively treated basal cell carcinoma of the skin or carcinoma in-situ of the uterine cervix
  • No combination antiretroviral therapy for HIV-positive patients
  • Recovered to < Common Toxicity Criteria for Adverse Effects (NCI CTCAE) grade 2 toxicities from prior therapy
  • More than 3 weeks since prior chemotherapy for metastatic disease (6 weeks for carmustine or mitomycin C)
  • At least 4 weeks since prior radiotherapy
  • Concurrent low-molecular weight heparin (LMWH) or full-dose coumadin allowed
  • International normalized ratio (INR) must be monitored as clinically indicated
  • No other concurrent investigational agents
  • No concurrent strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers, including the following:
  • Strong inhibitors: Amiodarone, erythromycin, clarithromycin, grapefruit juice, isoniazid, ketoconazole, itraconazole, or nefazodone
  • Patients taken off strong inhibitors allowed provided they have ≥ 1-week washout period
  • Strong inducers: Carbamazepine, pentobarbital, phenobarbital, phenytoin, Rifabutin, Rifampin, or St. John wort
  • Patients taken off strong inducers allowed provided they have ≥ 2-week washout period
  • No concurrent antiarrhythmics or other medications known to prolong QTc

Who cannot join

None listed.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Colorado Cancer Center - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • University of Colorado

    Denver, Colorado, 80217-3364

Other trials in United States

About this study

Official title: A Phase II Study of the Gamma Secretase Inhibitor RO4929097 in Previously Treated Metastatic Pancreas Cancer

This phase II trial is studying how well RO4929097 (gamma-secretase/Notch signalling pathway inhibitor RO4929097) works in treating patients with previously treated metastatic pancreatic cancer. RO4929097 may stop the growth of tumor cells by blocking some enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the 6-month survival of patients with previously treated metastatic pancreas cancer treated with gamma secretase RO4929097.

II. To determine the adverse events of RO4929097 in this patient population. III. To correlate changes in tumor markers with RO4929097 exposure.

SECONDARY OBJECTIVES:

  1. To evaluate the response rate and overall survival of this population treated with RO4929097.

II. To correlate clinical outcome with tumor markers (including stem cell markers) obtained from pre- and post- treatment biopsies. (exploratory) III. To assess variants in genes involved in RO4929097 disposition and their relation to RO4929097 exposure.

OUTLINE: This is a multicenter study.

Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 orally (PO) once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Patients may undergo tumor biopsy at baseline and on days 16 or 17 of course one for biomarker and other correlative studies. Blood samples may also collected at baseline and periodically during study for pharmacokinetic and angiogenesis marker studies.

After completion of study therapy, patients are followed up periodically for 2 years.

Being tested
gamma-secretase/Notch signalling pathway inhibitor RO4929097
Medical subject headings
Pancreatic Neoplasms

What participants receive

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

  • gamma-secretase/Notch signalling pathway inhibitor RO4929097Drug

    Also called R4733, RO4929097

    Given PO

Study groups in NCT01232829
Study groupRoleWhat they receive
Treatment (RO4929097)ExperimentalPatients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy at baseline and on days 16 or 17 of course one for biomarker and other correlative studies. Blood samples may also collected at baseline and periodically during study for pharmacokinetic and angiogenesis marker studies.
Receives: Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097

What is being measured

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

  1. Survival Rate

    The primary endpoint of the study was 6-month survival. The proportion of successes was estimated by the number of successes divided by the total number of evaluable patients.

    Measured: 6 months

Secondary outcomes (2)

  1. Survival

    Survival was estimated using the Kaplan-Meier (1958) method.

    Measured: From registration to death due to any cause, assessed up to 2 years

  2. Time to Disease Progression

    Eighteen patients were evaluable for the time to disease progression endpoint.

    Measured: From registration to documentation of disease progression, assessed up to 2 years

Timeline

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

  1. First posted2 Nov 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionJul 2012
  4. Study completionMay 2014

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01232829
Sponsor's protocol ID
NCI-2011-02537
Other IDs
NCI-2011-02537, CDR0000687335, 10-0273, 8490, U01CA070095, P30CA046934
Status last verified
Jun 2014
First submitted
30 Oct 2010
Last updated
26 Nov 2014
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing gamma-secretase/Notch signalling pathway inhibitor RO4929097 in people with Adenocarcinoma of the Pancreas and Recurrent Pancreatic Cancer, run by National Cancer Institute (NCI) at 3 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 47 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: finished, as of the sponsor's last update on 26 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Survival Rate (time frame: 6 months). 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 NCT01232829.

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 26 Nov 2014.

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