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Metastatic Pancreatic CancerPhase 2NCT01088815

Hedgehog Inhibitors for Metastatic Adenocarcinoma of the Pancreas

A Phase 2 study testing Gemcitabine, nab-Paclitaxel, GDC-0449 in people with Metastatic Pancreatic Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 is an open-label, single arm, multi-center, Phase II trial to evaluate the progression free survival in patients with metastatic adenocarcinoma of the pancreas treated with a hedgehog inhibitor (GDC-0449) in combination with chemotherapy (gemcitabine and nab-Paclitaxel). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Pancreatic Cancer
What is being tested?
Gemcitabine, nab-Paclitaxel, GDC-0449
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
98 participants
Where
3 sitesUnited States
Study dates
17 Sep 2010to 17 Feb 2018
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

  • Patient has histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. Patients with islet cells tumors are excluded. Biopsy within 14 days of starting treatment.
  • Patient has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan.
  • Patient has NOT received previous radiotherapy, surgery or chemotherapy or investigational drug therapy for the treatment of metastatic disease. If the patient received radiotherapy, chemotherapy or investigational therapy in the adjuvant setting it should be completed 3 weeks prior to enrollment. If a patient received gemcitabine in the adjuvant setting, tumor recurrence must have occurred at least six months after completing the last dose of gemcitabine
  • Age >18 years.
  • Life expectancy of greater than 1 month.
  • ECOG performance status 0 or 1 (Karnofsky >70%).
  • Patients must have adequate organ and marrow function

Who cannot join

  • Patient had received chemotherapy or radiotherapy for metastatic disease
  • Patient is receiving other investigational agents.
  • Patient has known brain metastases, unless previously treated and well controlled for at least three months (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or other agents used in the study.
  • Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible.
  • Uncontrolled illness including, but not limited to, ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure not controlled with medication, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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  • Pregnant women are excluded
  • Patient has undergone a major surgery, other than diagnostic surgery (i.e. surgery done to obtain a biopsy for diagnosis without removal of an organ) within four weeks prior to Day 1 of treatment on this study.
  • History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the patient at high risk from treatment complications

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21205

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Translational Genomics Research Institute (TGen)

    Scottsdale, Arizona, 85258

Other trials in United States

About this study

Official title: A Phase II Study of Gemcitabine and Nab-Paclitaxel in Combination With GDC-0449 (Hedgehog Inhibitor) in Patients With Previously Untreated Metastatic Adenocarcinoma of the Pancreas

This is an open-label, single arm, multi-center, Phase II trial to evaluate the progression free survival in patients with metastatic adenocarcinoma of the pancreas treated with a hedgehog inhibitor (GDC-0449) in combination with chemotherapy (gemcitabine and nab-Paclitaxel).

Read the detailed description

The emergence of new small molecules with capacity of blocking the Hedgehog signaling pathway provides a novel therapeutic approach in pancreatic adenocarcinoma treating the primary tumor, stroma, systemic metastases and pancreatic cancer stem cells by hedgehog pathway inhibition. This phase 2 clinical trial will evaluate the progression free survival (PFS) in patients with previously untreated metastatic pancreatic adenocarcinoma. We hypothesize that the combination of cytotoxic agents (gemcitabine and nab-paclitaxel) with the Hedgehog inhibitor GDC-0449 may increase PFS.

This study includes correlative studies to attempt to understand the stem cell biology and mechanism for any observed clinical benefits with the use of Hedgehog inhibitor GDC-0449. These include changes in the hedgehog pathway and changes in pancreatic cancer stem cell markers with pre and post treatment biopsies. The safety of GDC-0449 when combined with chemotherapy gemcitabine and nab-paclitaxel will also be assessed by evaluating adverse event rate.

Following the determination of eligibility patients will receive the following treatment:

  1. One cycle of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 (28 days cycle) then
  2. Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with oral GDC-0449 150 mg daily

Patients may continue on treatment regimen until they experience progressive disease or unacceptable toxicity, require palliative radiotherapy, withdraw consent or the physician feels it is not longer in their best interest to continue on treatment.

Being tested
Gemcitabine, nab-Paclitaxel, GDC-0449
Keywords
Adenocarcinoma, Hedgehog, Neoplasms, Digestive System Diseases, Neoplasms by Site, Digestive System Neoplasms, Neoplasms by Histologic Type, Pancreatic Neoplasms, Pancreatic Diseases, Carcinoma
Medical subject headings
Pancreatic Neoplasms, Adenocarcinoma, Neoplasms, Digestive System Diseases, Neoplasms by Site, Digestive System Neoplasms, Neoplasms by Histologic Type, Pancreatic Diseases

What participants receive

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

  • Gemcitabine, nab-Paclitaxel, GDC-0449Drug

    1. One cycle of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 (28 days cycle) then
    2. Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with oral GDC-0449 150 mg daily
Study groups in NCT01088815
Study groupRoleWhat they receive
Gemcitabine, nab-paclitaxel, GDC-0449ExperimentalGemcitabine and nab-Paclitaxel in combination with GDC-0449 (Vismodegib)
Receives: Drug: Gemcitabine, nab-Paclitaxel, GDC-0449

What is being measured

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

  1. Progression Free Survival With the Combination of GDC-0449 With Gemcitabine and Nab-paclitaxel.

    Number of months from time first therapy received to the earliest documented disease progression or death from any cause.

    Measured: 6 years

  2. Safety of Combination Therapy in Patients With Metastatic Adenocarcinoma of the Pancreas as Assessed by Number of Grade 3 or 4 Adverse Events

    Number of grade 3 or 4 adverse events as defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE v4.0) that occur after Cycle 2, Day 1

    Measured: 6 years

Secondary outcomes (4)

  1. Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Overall Survival

    Total number of months alive.

    Measured: 6 years

  2. Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Tumor Response

    Number of participants with complete (CR) or partial (PR) response as defined by RECIST criteria.

    Measured: 6 years

  3. Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Changes in Pancreatic Cancer Stem Cell

    Change in number of Pancreatic cancer stem cells in tissue and peripheral blood in tissue biopsy and peripheral blood.

    Measured: 6 years

  4. Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Hedgehog Signaling Pathway Downregulation

    Hedgehog signaling pathway downregulation as measured by Gli-1 and Patch expression

    Measured: 6 years

Timeline

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

  1. First posted17 Mar 2010 (estimated)
  2. Study start17 Sep 2010
  3. Primary completion1 Dec 2017
  4. Study completion17 Feb 2018

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
98 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01088815
Sponsor's protocol ID
J1013
Other IDs
NA_00036883
Status last verified
Apr 2019
First submitted
1 Mar 2010
Last updated
26 Apr 2019
Data monitoring committee
Yes

Publications

  • De Jesus-Acosta A, Sugar EA, O'Dwyer PJ, Ramanathan RK, Von Hoff DD, Rasheed Z, Zheng L, Begum A, Anders R, Maitra A, McAllister F, Rajeshkumar NV, Yabuuchi S, de Wilde RF, Batukbhai B, Sahin I, Laheru DA. Phase 2 study of vismodegib, a hedgehog inhibitor, combined with gemcitabine and nab-paclitaxel in patients with untreated metastatic pancreatic adenocarcinoma. Br J Cancer. 2020 Feb;122(4):498-505. doi: 10.1038/s41416-019-0683-3. Epub 2019 Dec 20.

    PubMed 31857726

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Gemcitabine, nab-Paclitaxel, GDC-0449 in people with Metastatic Pancreatic Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 7 inclusion and 9 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 Apr 2019. 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 Apr 2019). 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?

Progression Free Survival With the Combination of GDC-0449 With Gemcitabine and Nab-paclitaxel. (time frame: 6 years). 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 NCT01088815, 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 26 Apr 2019.

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