AzTrials
AzTrials

Recurrent Pancreatic CarcinomaPhase 2NCT01195415

Vismodegib and Gemcitabine Hydrochloride in Treating Patients With Advanced Pancreatic Cancer

A Phase 2 study testing Gemcitabine Hydrochloride, Laboratory Biomarker Analysis and Vismodegib in people with Recurrent Pancreatic Carcinoma and Stage IV Pancreatic Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

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

Official record
Search all trials

Trial summary

This pilot clinical trial studies vismodegib and gemcitabine hydrochloride in treating patients with advanced pancreatic cancer. Vismodegib may stop the growth of pancreatic cancer by blocking blow flow to the tumor. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Gemcitabine Hydrochloride, Laboratory Biomarker Analysis and Vismodegib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
Jun 2010to 10 Oct 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

  • Patients must have histologically or cytologically confirmed pancreas cancer
  • Patients must have metastatic disease or recurrent disease following surgical therapy
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan
  • Patients must have disease accessible for core needle biopsy both prior to initiation of therapy and on day 21 (+ or - 1 day) of GDC-0449 treatment
  • No previous systemic therapy for metastatic pancreas cancer is permitted; prior neoadjuvant or adjuvant therapy with chemotherapy and/or radiation is allowed provided that the last day of therapy was at least 6 months prior to registration
  • Life expectancy of greater than 12 weeks
Show all 17Show fewer
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 2.0 mg/dl
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal; < 5 x if liver involved in tumor
  • Creatinine < 2.0 mg/dl
  • The effects of GDC-0449 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because hedgehog (Hh) signal pathway inhibitors as well as gemcitabine are known to be teratogenic, women of child-bearing potential and men must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry, for the duration of study participation, and for at least 12 months post-treatment; for appropriate methods of contraception considered acceptable; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately;
  • Pregnancy testing: omen of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL beta-human chorionic gonadotropin [bHCG]) within 10-14 days and within 24 hours prior to the first dose of GDC-0449 (serum or urine); a pregnancy test (serum or urine) will be administered every 4 weeks if their menstrual cycles are regular or every 2 weeks if their cycles are irregular while on study within the 24-hour period prior to the administration of GDC-0449; a positive urine test must be confirmed by a serum pregnancy test; prior to dispensing GDC-0449, the investigator must confirm and document the patient's use of two contraceptive methods, dates of negative pregnancy test, and confirm the patient's understanding of the teratogenic potential of GDC-0449
  • Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450) may be enrolled with caution; GDC-0449 is a substrate of CYP3A4; however, the in vitro metabolic conversion of GDC-0449 is low; effects of cytochrome (CYP) inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. John's wart, and troglitazone) on clinical concentrations of GDC-0449 are unknown; likewise, the effects of strong inhibitors of CYP3A4 (e.g., clarithromycin, erythromycin, itraconazole, ketoconazole, nefazodone, and telithromycin) on GDC-0449 clinical concentrations are unknown, and caution should be exercised when dosing GDC-0449 concurrently with inhibitors of CYP3A4; in addition, GDC-0449 inhibits CYP2C8, CYP2C9, and CYP2C19 drug metabolism enzymes in vitro at concentrations that may be clinically relevant; therefore, caution should be exercised when dosing GDC-0449 concurrently with medications that are substrates of CYP2C8, CYP2C9, and CYP2C19 and have narrow therapeutic windows
  • Ability to understand and willingness to provide written informed consent

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 6 months prior to entering the study or those who have not recovered from adverse events due to agents administered more than 6 months earlier
  • Patients may not be receiving any other investigational agents
  • Patients with known brain metastases
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or other agents used in the study
  • Patients on anticoagulation with Coumadin are ineligible; however anticoagulation with enoxaparin is acceptable for study entry
  • Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption; patients must be able to swallow capsules
Show all 12Show fewer
  • Patients with clinically active liver disease, including active viral or other hepatitis or cirrhosis, are ineligible
  • Patients with uncontrolled hypomagnesemia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study
  • Patients with > grade 1 hyponatremia or hypocalcemia are excluded from this study
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because GDC-0449 is a Hh pathway inhibiting agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with GDC-0449, breastfeeding should be discontinued if the mother is treated with GDC-0449; these potential risks may also apply to other agents used in this study
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with GDC-0449; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

Other trials in United States

About this study

Official title: Cancer Stem Cells and Inhibition of Hedgehog Pathway Signaling in Advanced Pancreas Cancer: A Pilot Study of GDC-0449 in Combination With Gemcitabine

This pilot clinical trial studies vismodegib and gemcitabine hydrochloride in treating patients with advanced pancreatic cancer. Vismodegib may stop the growth of pancreatic cancer by blocking blow flow to the tumor. Gemcitabine hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vismodegib and gemcitabine hydrochloride may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To obtain tumor biopsies before and after therapy with GDC-0449 (vismodegib) to evaluate the effect of inhibition of hedgehog signaling on pancreatic cancer stem cells by: evaluating the tumor for number and percentage of pancreatic cancer stem cells before and after treatment with GDC-0449.

SECONDARY OBJECTIVES:

  1. To assess progression free survival (PFS) at 3 months following treatment with GDC-0449 and gemcitabine (gemcitabine hydrochloride).

II. To assess response rate to treatment and overall survival in patients with advanced pancreas cancer treated with GDC-0449 alone and in combination with gemcitabine.

III. To evaluate the toxicity of GDC-0449 alone and in combination with gemcitabine.

OUTLINE:

Patients receive vismodegib orally (PO) once daily (QD) on days 1-28 and gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15 (beginning in course 2). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks.

Being tested
Gemcitabine Hydrochloride, Laboratory Biomarker Analysis, Vismodegib
Medical subject headings
Pancreatic Neoplasms

What participants receive

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

  • Gemcitabine HydrochlorideDrug

    Also called dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • VismodegibDrug

    Also called Erivedge, GDC-0449, Hedgehog Antagonist GDC-0449

    Given PO

Study groups in NCT01195415
Study groupRoleWhat they receive
Treatment (vismodegib, gemcitabine hydrochloride)ExperimentalPatients receive vismodegib PO QD on days 1-28 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 (beginning in course 2). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Vismodegib

What is being measured

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

  1. Median Percent at Baseline and 3 Weeks in CD44+/ CD24+/ ESA+ Cells From Needle Biopsy Calculated Using FACS

    The median percentage of CD44+CD24+ESA+ cells from needle biopsy were calculated at baseline and at 3 weeks using FACS. The difference between the two time points was calculated.

    Measured: 3 weeks

Secondary outcomes (3)

  1. The Number of Participants With an Objective Best Response (CR + PR)

    The number of participants with either a complete response (CR) or a partial response (PR) will be calculated. A CR is defined as the disappearance of all target lesions. A PR is defined as at least a 30% decrease in the sum of the diameters of target lesions.

    Measured: Up to 4 weeks

  2. Median Progression Free Survival

    Median progression free survival was calculated for all treated patients. Assessed using the Kaplan-Meier method. The 95% confidence interval for this estimate will be computed using the Greenwood's formula.

    Measured: Up to 24 months

  3. Percentage of Treated Patients Experiencing Grade 3+ Toxicity Per National Cancer Institute Common Toxicity Criteria (CTC) Version 3.0

    Measured: Up to 4 weeks

Timeline

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

  1. First posted6 Sep 2010 (estimated)
  2. Study startJun 2010
  3. Primary completionJul 2013
  4. Study completion10 Oct 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
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01195415
Sponsor's protocol ID
NCI-2011-03746
Other IDs
NCI-2011-03746, UMCC 2010-003, 8417, P30CA046592
Status last verified
Aug 2017
First submitted
2 Sep 2010
Last updated
7 Aug 2017
Data monitoring committee
Yes

Publications

  • Kim EJ, Sahai V, Abel EV, Griffith KA, Greenson JK, Takebe N, Khan GN, Blau JL, Craig R, Balis UG, Zalupski MM, Simeone DM. Pilot clinical trial of hedgehog pathway inhibitor GDC-0449 (vismodegib) in combination with gemcitabine in patients with metastatic pancreatic adenocarcinoma. Clin Cancer Res. 2014 Dec 1;20(23):5937-5945. doi: 10.1158/1078-0432.CCR-14-1269. Epub 2014 Oct 2.

    PubMed 25278454

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Gemcitabine Hydrochloride, Laboratory Biomarker Analysis and Vismodegib in people with Recurrent Pancreatic Carcinoma and Stage IV Pancreatic Cancer, run by National Cancer Institute (NCI) at 1 site 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 17 inclusion and 12 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 7 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 7 Oct 2015). 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?

Median Percent at Baseline and 3 Weeks in CD44+/ CD24+/ ESA+ Cells From Needle Biopsy Calculated Using FACS (time frame: 3 weeks). 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 NCT01195415, which also lists 1 linked publication.

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 7 Aug 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in