Pancreatic Adenocarcinoma ResectableEarly Phase 1NEOPACHI-001NCT01713218
Effect on Tumor Perfusion of a Chemotherapy Combining Gemcitabine and Vismodegib Before Surgery in Pancreatic Cancer
A Early Phase 1 study testing gemcitabine, Vismodegib and Neoadjuvant chemotherapy in people with Pancreatic Adenocarcinoma Resectable, run by Jean-Luc Van Laethem at 2 sites in Belgium.
Trial summary
Pancreatic ductal adenocarcinoma (PDAC) has one of the worst prognoses of all human cancers and is considered as a sanctuary, resistant to most of the drugs used. Identification of new molecular targets involved in its pathogenesis is urgently needed and required both proper and innovative efficacy assessment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Adenocarcinoma Resectable
- What is being tested?
- gemcitabine, Vismodegib and Neoadjuvant chemotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 2 sitesBelgium
- Study dates
- Dec 2012to Dec 2016
- Phase
- Early 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
- Histo(cyto)logically proven ductal pancreatic adenocarcinoma
- Resectable or potentially resectable tumor; resectability assessed during a multidisciplinary meeting with expert surgeon and radiologist
- First line chemotherapy
- Age > 18 years
- WHO performance status (PS) grade 0 or 1;
- Absolute neutrophil count > 1.5 x 10 9 / L, platelets > 100 x 10 9/ L, creatinine clearance (Cockcroft and Gault formula) > 60 ml/min, haemoglobin level > 10 g/dl (transfusions authorized), bilirubin<1.5 g/dl;
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- Optimal biliary drainage;
- Women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or tubal ligation of who has not been naturally postmenopausal for at least 24 consecutive months, must have a negative serum or urine pregnancy test prior to treatment. All WCBP, all sexually active male patients, and all partners of patients must agree to use adequate methods of birth control throughout the study;
- Signed written informed consent.
Who cannot join
- Locally advanced non resectable or metastatic pancreatic adenocarcinoma
- Previous anticancer therapy for the pancreatic adenocarcinoma
- Biliary obstruction without endoscopic biliary drainage
- Any contre-indication for surgery
- Prior malignancy (except non-melanoma skin cancer, and in situ carcinoma of the uterine cervix treated with a curative intent and any other tumor in complete remission with a disease-free interval > 3 years)
- Uncontrolled congestive heart failure or angina pectoris, myocardial infarction within 1 year prior to study entry, uncontrolled hypertension (systolic pressure > 160 mm or diastolic pressure > 100 mm under well conducted antihypertensive treatment), QT prolongation
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- Major uncontrolled infection
- Severe hepatic impairment
- Any medical, psychological, or social condition, which, in the opinion of the investigator, could hamper patient's compliance to the study protocol and/or assessment/interpretation of the data
- Pregnant or lactating women, or patients of both genders with procreative potential not using adequate contraceptive methods
- Patients receiving or having received any investigational treatment within 4 weeks prior to study entry, or participating to another clinical study;Subject previously enrolled into this study.
Trial locations and contacts
2 sites in 1 country.
Jean-Luc Van Laethem, MD, PhD contact
Belgium2 sites
Erasme University Hospital (ULB)
Brussels, 1070
Jean-Luc Van Laethem, MD, PhD, jl.vanlaethem@erasme.ulb.ac.be
Jean-Luc Van Laethem, MD, PhD
Antwerp University Hospital (UZA)
Edegem, Antwerpen, 2650
Marc Peeters, MD,PhD, marc.peeters@uza.be
Marc Peeters, MD, PhD
About this study
Official title: Evaluation of Tumoral Perfusion Modification by Dynamic Imaging After Neoadjuvant Chemotherapy Combining Gemcitabine and a Hedgehog Inhibitor (Vismodegib) in Patients With Resectable Pancreatic Adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) has one of the worst prognoses of all human cancers and is considered as a sanctuary, resistant to most of the drugs used. Identification of new molecular targets involved in its pathogenesis is urgently needed and required both proper and innovative efficacy assessment.
This proof-of-concept trial is studying the "dynamic" tumor response after the administration of a short course (4 weeks) neoadjuvant combination of gemcitabine and a Hedgehog inhibitor (Vismodegib) before surgery in patients with operable pancreatic cancer.
Read the detailed description
Pancreatic cancer is characterized by a high stromal density and is a hypoperfused tumor, precluding cytotoxics delivery to the epithelial tumoral compartment. There is thus a rationale for combining chemotherapy and antistromal drugs like Hedgehog inhibitors. Targeting the resectable primary tumor offers an appropriate setting to (1) evaluate and monitor early treatment effects on the tumor, (2) correlate dynamic imaging changes (perfusion and diffusion coefficient) to pre- and post-therapeutic tissue changes, (3) identify specific predictive biomarkers for the drugs used (i.e. gemcitabine transporters and Hedgehog pathway genes and proteins) and (4) assess if this early "dynamic and biomolecular response" can predict treatment benefit and patient outcome.
- Conditions
- Pancreatic Adenocarcinoma Resectable
- Being tested
- gemcitabine, Vismodegib, Neoadjuvant chemotherapy
- Keywords
- Pancreas, Cancer, Hedgehog inhibitor, Neoadjuvant chemotherapy, Dynamic imaging
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gemcitabineDrug
Also called GEMZAR
Administrated intravenously at a dose of 1000 mg/m2 over 30 minutes weekly, week 1 to 4
VismodegibDrug
Also called GDC-0449
150 mg capsule, oral, once daily
Neoadjuvant chemotherapyProcedure or surgery
Combination of gemcitabine and Vismodegib during a window interval (4 weeks) before surgery
| Study group | Role | What they receive |
|---|---|---|
| Gemcitabine+Vismodegib | Experimental | Neoadjuvant chemotherapy combining gemcitabine and Vismodegib during 4 weeks before surgery Receives: Drug: gemcitabine; Drug: Vismodegib; Procedure: Neoadjuvant chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
"Dynamic" tumor response rate as defined by a 20% modification of tumoral perfusion and cellular density parameters.
In order to detect changes in the tumor microenvironment and to monitor treatment efficacy, Dynamic Contrast-Enhanced-Magnetic Resonance Imaging (DCE-MRI) and Diffusion Weighted-Magnetic Resonance Imaging (DW-MRI) constitute tools more and more used. The acquired data can be analyzed using a pharmacokinetic model to obtain quantitative parameters relative to tissue perfusion and vascular permeability (Ktrans, a volume transfer constant of contrast agent between blood plasma and the extravascular extracellular space; Apparent Diffusion Coefficient as a surrogate marker of tissue cellularity). DCE/DW-MRI will be achieved weekly before each neoadjuvant chemotherapy treatment and before surgery. Each patient will be his/her own control by comparing serial imaging results with those of the baseline MRI.
Measured: 4 weeks (duration of the neoadjuvant chemotherapy).
Secondary outcomes (1)
Number of participants with adverse events as assessed by National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0.
Number of participants with (serious) adverse events will be considered as a measure of safety of the whole therapeutic sequence (gemcitabine + Hedgehog inhibitor+ surgery).
Measured: End of study follow-up (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.
- First posted24 Oct 2012 (estimated)
- Study startDec 2012
- Primary completionJun 2014 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic Adenocarcinoma ResectableStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jean-Luc Van Laethem
- Sponsor type
- University, hospital or other
- Collaborators
- Roche Pharma AG
- Responsible party
- Sponsor-investigator, Jean-Luc Van Laethem, Erasme University Hospital
- Investigators
- Jean-Luc Van Laethem, MD, PhD, Principal investigator, Erasme University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01713218
- Sponsor's protocol ID
- 2012-003516-31
- Acronym
- NEOPACHI-001
- Status last verified
- Oct 2012
- First submitted
- 17 Oct 2012
- Last updated
- 24 Oct 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Tumoral Perfusion Modification by Dynamic Imaging After Neoadjuvant Chemotherapy Combining Gemcitabine and a Hedgehog Inhibitor (Vismodegib) in Patients With Resectable Pancreatic Adenocarcinoma
- ClinicalTrials.gov ID
- NCT01713218
- Acronym / sponsor ID
- NEOPACHI-001 / 2012-003516-31
- Conditions
- Pancreatic Adenocarcinoma Resectable
- Keywords
- Pancreas, Cancer, Hedgehog inhibitor, Neoadjuvant chemotherapy, Dynamic imaging
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- Jean-Luc Van LaethemUniversity, hospital or other
- Collaborators
- Roche Pharma AG
- Study start
- Dec 2012
- Primary completion
- Jun 2014 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 24 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pancreatic ductal adenocarcinoma (PDAC) has one of the worst prognoses of all human cancers and is considered as a sanctuary, resistant to most of the drugs used. Identification of new molecular targets involved in its pathogenesis is urgently needed and required both proper and innovative efficacy assessment.
This proof-of-concept trial is studying the "dynamic" tumor response after the administration of a short course (4 weeks) neoadjuvant combination of gemcitabine and a Hedgehog inhibitor (Vismodegib) before surgery in patients with operable pancreatic cancer.
Detailed description
Pancreatic cancer is characterized by a high stromal density and is a hypoperfused tumor, precluding cytotoxics delivery to the epithelial tumoral compartment. There is thus a rationale for combining chemotherapy and antistromal drugs like Hedgehog inhibitors. Targeting the resectable primary tumor offers an appropriate setting to (1) evaluate and monitor early treatment effects on the tumor, (2) correlate dynamic imaging changes (perfusion and diffusion coefficient) to pre- and post-therapeutic tissue changes, (3) identify specific predictive biomarkers for the drugs used (i.e. gemcitabine transporters and Hedgehog pathway genes and proteins) and (4) assess if this early "dynamic and biomolecular response" can predict treatment benefit and patient outcome.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gemcitabine+Vismodegib | Experimental | Drug: gemcitabine, Drug: Vismodegib, Procedure: Neoadjuvant chemotherapyNeoadjuvant chemotherapy combining gemcitabine and Vismodegib during 4 weeks before surgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histo(cyto)logically proven ductal pancreatic adenocarcinoma
- Resectable or potentially resectable tumor; resectability assessed during a multidisciplinary meeting with expert surgeon and radiologist
- First line chemotherapy
- Age > 18 years
- WHO performance status (PS) grade 0 or 1;
Key exclusion criteria (11 listed)
- Locally advanced non resectable or metastatic pancreatic adenocarcinoma
- Previous anticancer therapy for the pancreatic adenocarcinoma
- Biliary obstruction without endoscopic biliary drainage
- Any contre-indication for surgery
- Prior malignancy (except non-melanoma skin cancer, and in situ carcinoma of the uterine cervix treated with a curative intent and any other tumor in complete remission with a disease-free interval > 3 years)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| gemcitabineAlso: GEMZARAdministrated intravenously at a dose of 1000 mg/m2 over 30 minutes weekly, week 1 to 4 | Drug | Gemcitabine+Vismodegib |
| VismodegibAlso: GDC-0449150 mg capsule, oral, once daily | Drug | Gemcitabine+Vismodegib |
| Neoadjuvant chemotherapyCombination of gemcitabine and Vismodegib during a window interval (4 weeks) before surgery | Procedure or surgery | Gemcitabine+Vismodegib |
Primary outcome
"Dynamic" tumor response rate as defined by a 20% modification of tumoral perfusion and cellular density parameters.
Time frame: 4 weeks (duration of the neoadjuvant chemotherapy).
In order to detect changes in the tumor microenvironment and to monitor treatment efficacy, Dynamic Contrast-Enhanced-Magnetic Resonance Imaging (DCE-MRI) and Diffusion Weighted-Magnetic Resonance Imaging (DW-MRI) constitute tools more and more used. The acquired data can be analyzed using a pharmacokinetic model to obtain quantitative parameters relative to tissue perfusion and vascular permeability (Ktrans, a volume transfer constant of contrast agent between blood plasma and the extravascular extracellular space; Apparent Diffusion Coefficient as a surrogate marker of tissue cellularity). DCE/DW-MRI will be achieved weekly before each neoadjuvant chemotherapy treatment and before surgery. Each patient will be his/her own control by comparing serial imaging results with those of the baseline MRI.
1 secondary outcome
Number of participants with adverse events as assessed by National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0.
Time frame: End of study follow-up (up to 2 years).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean-Luc Van Laethem, MD, PhD contact
Jean-Luc Van Laethem, MD, PhD principal investigator
Erasme University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing gemcitabine, Vismodegib and Neoadjuvant chemotherapy in people with Pancreatic Adenocarcinoma Resectable, run by Jean-Luc Van Laethem at 2 sites in Belgium.
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 9 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 24 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Belgium. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jean-Luc Van Laethem, MD, PhD (jl.vanlaethem@erasme.ulb.ac.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
"Dynamic" tumor response rate as defined by a 20% modification of tumoral perfusion and cellular density parameters. (time frame: 4 weeks (duration of the neoadjuvant chemotherapy).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Oct 2012.