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Pancreatic CancerPhase 1/2MATRIXNCT02358161

Phase I/II Study of LDE225 With Gemcitabine and Nab-paclitaxel in Patients With Pancreatic Cancer

A Phase 1/2 study testing gemcitabine and nab paclitaxel in people with Pancreatic Cancer, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.

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

The 5 year survival of patients with locally advanced or metastatic pancreatic cancer is less than 5 %. Since the introduction of gemcitabine, further advances in therapy in the advanced/metastatic setting have been extremely slow. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pancreatic Cancer
What is being tested?
gemcitabine and nab paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
1 siteNetherlands
Study dates
Sep 2015to Jan 2019
Phase
Phase 1/2
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

  • Patients must provide written informed consent according to International Conference on Harmonisation of technical requirements for registration og pharmaceuticals for human use (ICH)/Good cClinical Practice (GCP), and national/local regulations prior to any screening procedures.
  • Male or female adult patients (> 18 years)
  • Patients with histologically/cytologically confirmed diagnosis of pancreatic ductal adenocarcinoma.
  • a. Phase I: patients with non resectable or metastasized pancreatic ductal adenocarcinoma.
  • Phase II: patients with non resectable or metastasized pancreatic ductal adenocarcinoma not pre-treated with chemotherapy or radiotherapy, unless adjuvant treatment with gemcitabine > 6 months prior to inclusion.
  • Measurable disease as assessed by RECIST 1.1 (Response Evaluation Criteria In Solid Tumors) .
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  • ECOG (Eastern Cooperative Oncology Group) (WHO) performance status 0-2
  • Patient has adequate bone marrow and organ function . Patient is able to swallow and retain oral medication
  • 9. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule;

Who cannot join

  • History of hypersensitivity to LDE225, or to drugs of similar chemical classes.
  • Patient has received previous treatment with smoothened inhibitors.
  • Patients with known CNS (Central Nervous System) metastases or a primary CNS malignancy.
  • Patients who have neuromuscular disorders or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as HMG CoA (3-hydroxy-3-methyl-glutaryl Coenzyme A) inhibitors (statins), clofibrate and gemfibrozil.
  • Patients who are planning on embarking on new physical activities, such as strenuous exercise, that can result in significant increases in plasma CK (Creatine Kinase) levels while on study treatment.
  • Patients who require the use of coumarin derivates cannot be enrolled as LDE225 is a competitive inhibitors of CYP2C9 based on in-vitro data.
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  • Patients with chronic use of corticosteroids
  • Patients who are not willing to avoid consumption of Seville oranges, grapefruit or grapefruit juice grapefruit hybrids, pomelos and exotic citrus fruits during the entire study and preferably 7 days before the first dose of study medications, due to potential CYP3A4 interaction with the study medications.
  • Patients who are not willing to stop taking herbal medications at least 7 days prior to the first dose of study treatment.
  • Patient is currently being treated with drugs known to be strong inhibitors or inducers of CYP3A4/5, which cannot be discontinued or switched to a different medication 7 days prior to starting study treatment and for the duration of the study..
  • Current medical history of the following:
  • History of or presence of clinically significant uncontrolled ventricular or atrial tachyarrhythmia
  • Clinically significant resting bradycardia (< 45 beats per minute) or any primary of secondary heart block
  • History of unstable angina pectoris
  • Clinically significant cardio-vascular disease (e.g. congestive heart failure NYHA Class III-IV (New York Heart Association), atherosclerosis, labile hypertension or uncontrolled hypertension
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive HCG (Human Chorionic Gonadotropin) laboratory test
  • Patients who are not willing to apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment.
  • Sexually active males who are unwilling to use a condom during intercourse while taking drug and for 6 months after stopping investigational medications and agree not to father a child in this period. Patients who in the investigators' opinion may be unwilling, unable or unlikely to comply with requirements of the study protocol
  • Patient is currently receiving increasing or chronic treatment with corticosteroids ((≥ the anti-inflammatory potency of 4mg dexamethasone) or another immunosuppressive agent.
  • Patient has been treated with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated before enrollment, may be continued
  • Patient who has received targeted therapy or immunotherapy ≤ 3 weeks (6 weeks for monoclonal antibodies) prior to starting study drug or who have not recovered to grade 1 or better from related side effects of such therapy
  • Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of LDE225 (e.g., ulcerative colitis, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
  • Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment contraindicate patient participation in the clinical study.
  • HIV-positive patients on combination antiretroviral therapy.
  • Patients who in the investigators' opinion may be unwilling, unable or unlikely to comply with requirements of the study protocol

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Academic Medical Center

    Amsterdam, 1105 AZ

Other trials in Netherlands

About this study

Official title: Phase I/II Study of LDE225 in Combination With Gemcitabine and Nab-paclitaxel in Patients With Locally Advanced or Metastasized Pancreatic Cancer

The 5 year survival of patients with locally advanced or metastatic pancreatic cancer is less than 5 %. Since the introduction of gemcitabine, further advances in therapy in the advanced/metastatic setting have been extremely slow. Numerous phase III studies have evaluated different gemcitabine-based regimens as first-line therapy, but in most cases, any observed benefits have been small and restricted to patients with a good performance status (PS). Recently two new chemotherapy combination schedules, FOLFIRINOX and Gemcitabine + nab-paclitaxel demonstrated a significant survival improvement compared to gemcitabine alone. Nab-paclitaxel is especially interesting because it is able to break-down the tumor matrix and increases the concentration of cytotoxic drugs in the tumor.

Our study will explore the modification of the desmoplastic reaction seen in pancreatic cancer using two approaches, targeting tumor stroma by nab-paclitaxel and the hedgehog inhibitor LDE225 and targeting the tumor cells with gemcitabine and nab-paclitaxel.

Read the detailed description

Growing body of evidence suggests that the stroma is not only a mechanical barrier that may prevent efficient delivery of various anticancer therapies to the tumor, but also constitutes a dynamic compartment of pancreatic tumors that is critically involved in tumor formation, progression and metastasis. Thus, targeting both tumor stroma and cancer cells could be a lucrative strategy to increase the efficacy of our therapeutic approach.

In the present study we want to explore the safety and activity of the chemotherapy combination: Gemcitabine + nab-paclitaxel + LDE225. LDE225 is a hedgehog inhibitor with promising antitumor activity in several cancer models, including pancreatic cancer. One of the main activities is also the degradation of the tumor matrix.

Patients with locally advanced or metastatic pancreatic cancer will be treated with fixed doses of gemcitabine + nab-paclitaxel, the same doses used in the recently presented phase III study (von Hoff American Society of Clinical Oncology ASCO 2013). In the phase I part of the study LDE225 will be added according to standard dose escalation strategy for phase I studies, and at the maximum tolerated dose (MTD) patients will be treated in the phase II part of the study.

Being tested
gemcitabine and nab paclitaxel
Keywords
Pancreatic cancer, LDE225, Gemcitabine, nab paclitaxel
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 and nab paclitaxelDrug

    Also called Gemzar, Abraxane

    DLT adn MTD of LED225 co-administered with fixed doses of gemcitabine and nab-paclitaxel in patients with advanced or metastasized pancreatic cancer

Study groups in NCT02358161
Study groupRoleWhat they receive
LDE225ExperimentalDLT adn MTD of LED225 co-administered with fixed doses of gemcitabine and nab-paclitaxel in patients with advanced or metastasized pancreatic cancer.
Receives: Drug: gemcitabine and nab paclitaxel

What is being measured

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

  1. Dose limiting Toxicity (DLT) and MTD of LDE225 co-administered with gemcitabine and nab-paclitaxel

    Phase I: DLT and MTD of LDE225 co-administered with fixed doses of gemcitabine and nab-paclitaxel in patients with advanced or metastasized pancreatic cancer

    Measured: first six weeks after start treatment

Secondary outcomes (2)

  1. Median survival

    Measured: 1 year

  2. Progression free survival

    Measured: 6 months

Timeline

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

  1. First posted6 Feb 2015 (estimated)
  2. Study startSep 2015
  3. Primary completionSep 2018
  4. Study completionJan 2019

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02358161
Sponsor's protocol ID
AMCMEDONC 2013-215
Other IDs
2013-002370-51
Acronym
MATRIX
Status last verified
Jan 2020
First submitted
15 Apr 2014
Last updated
9 Jan 2020
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing gemcitabine and nab paclitaxel in people with Pancreatic Cancer, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.

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 25 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 9 Jan 2020. 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 Netherlands. 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 combined 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.

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Dose limiting Toxicity (DLT) and MTD of LDE225 co-administered with gemcitabine and nab-paclitaxel (time frame: first six weeks after start treatment). 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 NCT02358161.

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 9 Jan 2020.

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