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Acinar Cell Adenocarcinoma of the PancreasPhase 1NCT01537107

Sirolimus and Vismodegib in Treating Patients With Solid Tumors or Pancreatic Cancer That is Metastatic or Cannot Be Removed By Surgery

A Phase 1 study testing vismodegib, sirolimus and positron emission tomography in people with Acinar Cell Adenocarcinoma of the Pancreas and Duct Cell Adenocarcinoma of the Pancreas, run by Mayo Clinic 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 I trial studies the side effects and the best dose of sirolimus when given together with vismodegib in treating patients with solid tumors or pancreatic cancer that is metastatic or cannot be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
vismodegib, sirolimus and positron emission tomography
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
3 sitesUnited States
Study dates
5 Mar 2012to 27 Jun 2018
Phase
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

  • COHORT I (DOSE ESCALATION): histologic proof of cancer that is now unresectable, not amenable to any other standard therapies, or patient refuses standard therapy
  • COHORT II (MTD): metastatic adenocarcinoma of the pancreas and tumor amenable to biopsies; prior systemic treatment for metastatic disease is allowed
  • Absolute neutrophil count (ANC) => 1500/uL
  • Platelet >= 100,000/uL
  • Total bilirubin =< upper limit of normal (ULN) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 3 x ULN
  • Creatinine =< 1.5 x ULN
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  • Hemoglobin >= 9.0 g/dL
  • Prothrombin time (PT)/international normalized ratio (INR) < 1.25 x ULN (Cohort II [MTD] only)
  • Cholesterol < Common Terminology Criteria for Adverse Events (CTCAE) grade 3
  • Triglycerides < CTCAE grade 2
  • Magnesium >= lower limit of normal (LLN) and =< ULN
  • Ability to provide informed consent
  • Willing to return to Mayo Clinic for follow up
  • Life expectancy >= 12 weeks
  • Cohort II (MTD) only - Translational Research: Willing to provide the biologic specimens as required by the protocol; Note: this is part of the mandatory translational research component
  • Women of childbearing potential only: Negative serum pregnancy test done =< 7 days prior to registration; NOTE: female subjects who are pregnant or nursing are excluded from this study; there is no specific mitigation strategy for vismodegib toxicity; however, male patients should be made aware of it during the consent process; although this effect is expected to be reversible with discontinuation of dosing, long-term effects on male fertility cannot be excluded at this time
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • Able to swallow or have medication administered through a G-tube and absorb the medication
  • Participant agrees to use acceptable form of contraception during the study and for up to 7 months after last study drug dose
  • Acceptable forms of contraception:
  • Latex condom (always used with spermicide)
  • Diaphragm (always used with spermicide)
  • Cervical cap (always used with spermicide)
  • Acceptable forms of secondary contraception, when used along with a barrier method:
  • Hormonal contraception methods, including pills, patches, rings, or injections except progestin-only containing pills (i.e. "Mini-pill")
  • Tubal ligation
  • Partner's vasectomy
  • Intrauterine device (non-progesterone T)
  • Vaginal sponge (containing spermicide)
  • Other acceptable forms:
  • 100% commitment to abstinence
  • Unacceptable forms of contraception for women of childbearing potential:
  • Oral contraception containing progestins only
  • Intrauterine device (IUD) progesterone T
  • Female condom
  • Natural family planning (rhythm method) or breastfeeding
  • Fertility awareness
  • Withdrawal
  • Cervical shield
  • Willing not to smoke
  • Willing to complete a pill diary each day

Who cannot join

  • COHORT I (DOSE ESCALATION): Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes mellitus or psychiatric illness/social situations that would limit compliance with study requirements
  • Any of the following prior therapies:
  • Chemotherapy =< 4 weeks prior to registration
  • Mitomycin C/nitrosoureas =< 6 weeks prior to registration
  • Immunotherapy =< 4 weeks prior to registration
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  • Biologic therapy =< 4 weeks prior to registration
  • Radiation therapy =< 4 weeks prior to registration
  • Radiation to > 25% of bone marrow
  • Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
  • New York Heart Association classification III or IV
  • Uncontrolled Seizure Disorder
  • Central nervous system (CNS) metastases if not stable for at least 2-3 months based on imaging, clinical assessment, use of steroids, or seizure disorder
  • Any of the following:
  • Pregnant women
  • Nursing women
  • This study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) or receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Receiving any medications or substances that are strong or moderate inhibitors of cytochrome P450 3A4 (CPY450 3A4); use of the following strong or moderate inhibitors are prohibited:
  • Strong Inhibitors of CYP3A4: Indinavir, Nelfinavir, Ritonavir, Clarithromycin, Itraconazole, Ketoconazole, Nefazodone, Saquinavir, Telithromycin
  • Moderate Inhibitors of CYP3A4: Aprepitant, Erythromycin, Fluconazole, Grapefruit juice, Verapamil, Diltiazem
  • Receiving any medications or substances that are inducers of CYP450 3A4
  • Inducers of CYP3A4: Efavirenz, Nevirapine, Carbamazepine, Modafinil, Phenobarbital, Phenytoin, Pioglitazone, Rifabutin, Rifampin, St. John's wort
  • Receiving any medications or substances that are strong or moderate inhibitors of CYP450 CYP2C8
  • Strong or Moderate Inhibitors of CYP2C8: Gemfibrozil, Trimethoprim
  • Receiving any medications or substances that are inducers of CYP450 2C8
  • Inducer of CYP2C8: Rifampin
  • Receiving any medications or substances that are strong or moderate inhibitors of CYP450 CYP2C9
  • Strong or Moderate Inhibitors of CYP2C9: Fluconazole, Amiodarone
  • Receiving any medications or substances that are inducers of CYP450 2C9
  • Inducers of CYP2C9: Rifampin, Secobarbital
  • Immunocompromised patients (other than that related to the use of corticosteroids) including patients receiving highly active antiretroviral therapy (HAART) treatment
  • Active other malignancy, excepting non-melanotic skin cancer or carcinoma-in situ (e.g. of cervix, breast prostate); if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer
  • History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjogren's syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test)
  • Prior therapy with a hedgehog inhibitor

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Mayo Clinic Campus in Florida

    Jacksonville, Florida, 32224

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Mayo Clinic Campus in Arizona

    Scottsdale, Arizona

Other trials in United States

About this study

Official title: Phase I Trial of The Combination of Vismodegib and Sirolimus

This phase I trial studies the side effects and the best dose of sirolimus when given together with vismodegib in treating patients with solid tumors or pancreatic cancer that is metastatic or cannot be removed by surgery. Sirolimus and vismodegib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximally tolerated dose (MTD) of the combination of vismodegib and sirolimus in unresectable solid tumors. (Cohort I)

SECONDARY OBJECTIVES:

  1. To describe the adverse event profile associated with this treatment combination.

II. To describe the tumor responses to treatment combination.

CORRELATIVE OBJECTIVES:

  1. To assess the effect of the sirolimus and vismodegib combination on selected biomarkers in tumor biopsies of patients with metastatic pancreatic cancer.

II. To assess the effect of the combination of vismodegib and sirolimus on fludeoxyglucose F 18 (F18-FDG) positron emission tomography (PET) or PET/computed tomography (CT) imaging in Cohort II (MTD) patients with metastatic pancreatic cancer.

III. To study the association of clinical (toxicity and/or tumor response or activity) with the biologic (pharmacodynamic) results obtained by examining tissue biopsies and PET or PET/CT imaging from the same patients.

OUTLINE: This is a dose-escalation study of sirolimus.

Patients receive sirolimus orally (PO) once daily (QD) and vismodegib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 months.

Medical subject headings
Pancreatic Neoplasms

What participants receive

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

  • vismodegibDrug

    Also called GDC-0449

    Given PO

  • sirolimusDrug

    Also called Rapamune, rapamycin, RAPA

    Given PO

  • positron emission tomographyProcedure or surgery

    Also called FDG-PET, PET, PET scan, tomography, emission computed

    Correlative studies

  • computed tomographyProcedure or surgery

    Also called tomography, computed

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

  • fludeoxyglucose F 18Radiation

    Also called 18FDG, FDG

    Correlative studies

Study groups in NCT01537107
Study groupRoleWhat they receive
Treatment (enzyme inhibitor therapy)ExperimentalPatients receive sirolimus PO QD and vismodegib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: vismodegib; Drug: sirolimus; Procedure: positron emission tomography; Procedure: computed tomography; Other: pharmacological study; Other: laboratory biomarker analysis; Radiation: fludeoxyglucose F 18

What is being measured

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

  1. MTD (Cohort I) ) and toxicity profile of combination of vismodegib plus sirolimus every 28 days.

    MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). DLT will be defined as a course 1 adverse event (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) attributed (definitely, probably, or possibly) to the study treatment. MTD will be examined in an exploratory and hypothesis generating fashion.

    Measured: 120 days

Secondary outcomes (3)

  1. Adverse events (AEs) profile in terms of the number and severity of all adverse events (overall, by dose-level, and by tumor group) at baseline, at each dose level and at 30 days after completion of study treatment

    Measured: 120 days

  2. Time to treatment failure

    Measured: 120 days

  3. Antitumor effect of molecularly targeted agents non-invasively by F18-FDG PET or PET/CT (Cohort II)

    Measured: 120 days

Timeline

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

  1. First posted23 Feb 2012 (estimated)
  2. Study start5 Mar 2012
  3. Primary completion27 Jun 2018
  4. Study completion27 Jun 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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01537107
Sponsor's protocol ID
MC1111
Other IDs
NCI-2011-03809
Status last verified
Apr 2019
First submitted
14 Feb 2012
Last updated
8 Apr 2019
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing vismodegib, sirolimus and positron emission tomography in people with Acinar Cell Adenocarcinoma of the Pancreas and Duct Cell Adenocarcinoma of the Pancreas, run by Mayo Clinic 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 41 inclusion and 36 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 8 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 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.

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?

MTD (Cohort I) ) and toxicity profile of combination of vismodegib plus sirolimus every 28 days. (time frame: 120 days). 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 NCT01537107.

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 8 Apr 2019.

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