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Cholangiocarcinoma of the GallbladderPhase 1NCT00949949

Everolimus, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients With Unresectable Solid Tumors Refractory to Standard Therapy

A Phase 1 study testing everolimus, gemcitabine hydrochloride and cisplatin in people with Cholangiocarcinoma of the Gallbladder and Localized Gallbladder Cancer, 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 randomized phase I trial is studying the side effects and best dose of everolimus, gemcitabine hydrochloride, and cisplatin in treating patients with unresectable solid tumors refractory to standard therapy. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
everolimus, gemcitabine hydrochloride and cisplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
3 sitesUnited States
Study dates
Sep 2009to Jul 2014
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

  • Histologic proof of cancer that is now unresectable and refractory to or refused all standard treatment for the disease; exception: cancers in which gemcitabine is considered an appropriate initial treatment option
  • Cohort III (MTD) Only: Patients with histologic proof of metastatic cholangiocarcinoma or gallbladder carcinoma who have not had previous treatment for metastatic disease or who received gemcitabine >= 6 months ago as part of adjuvant therapy
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Platelet (PLT) >= 100,000/uL
  • Total bilirubin =< 1.5 x Institutional upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x upper limit of normal (ULN) (=< 5x ULN in patients with liver metastases)
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  • Creatinine =< 1.5 x Institutional ULN
  • Alkaline phosphatase =< 5 x Institutional ULN
  • Hemoglobin (Hgb) >= 9.0 g/dL
  • International normalized ratio (INR) and Partial thromboplastin time (PTT) =< 3.0 x ULN (anticoagulation is allowed if target INR =< 3.0 x ULN on a stable dose of warfarin or on a stable dose of low-molecular-weight [LMW] heparin for > 2 weeks at time of registration)
  • Fasting serum glucose < 1.5 x ULN
  • Fasting serum cholesterol =< 300 mg/dL OR =< 7.75 mmol/L AND fasting triglycerides =< 2.5 x ULN; NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2
  • Ability to provide informed consent
  • Willingness to return to Mayo Clinic for follow up
  • Life expectancy >= 12 weeks
  • Women of childbearing potential only: Negative serum pregnancy test done =< 7 days prior to registration

Who cannot join

  • 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, or psychiatric illness/social situations that would limit compliance with study requirements
  • Clinically significant cardiac disease, especially history of myocardial infarction =< 6 months, or congestive heart failure (New York Heart Association [NYHA] classification III or IV) requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • Patients taking strong inhibitors or inducers of CYP3A4
  • Prior therapy with everolimus
  • Any of the following prior therapies:
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  • Chemotherapy =< 4 weeks prior to registration
  • Mitomycin C/nitrosoureas =< 6 weeks prior to registration
  • Immunotherapy =< 4 weeks prior to registration
  • Biological therapy =< 4 weeks prior to registration
  • Radiation therapy =< 4 weeks prior to registration
  • Radiation to > 25% of bone marrow prior to registration
  • Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
  • CNS metastases that are not stable for at least 4 weeks prior to registration based on imaging, clinical assessment, and use of steroids
  • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive
  • Current active other malignancy, except non-melanoma skin cancer or carcinoma-in-situ of the cervix
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
  • Severely impaired lung function (i.e., forced expiratory volume in one second [FEV1] < 1 liter)
  • Received immunization with attenuated live vaccines =< 7 days prior to study entry or during study period; NOTE: close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus; examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines
  • Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C); Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: Phase I Trial of Everolimus, Gemcitabine, and Cisplatin for Patients With Solid Tumors Refractory to Standard Therapy

This randomized phase I trial is studying the side effects and best dose of everolimus, gemcitabine hydrochloride, and cisplatin in treating patients with unresectable solid tumors refractory to standard therapy. Drugs used in chemotherapy, such as everolimus, gemcitabine hydrochloride, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

Read the detailed description

OBJECTIVES:

  1. To determine the maximally tolerated dose (MTD) of concurrently administered everolimus and gemcitabine (gemcitabine hydrochloride) in patients with advanced, refractory solid tumors (two-agent MTD).

II. To determine the maximally tolerated dose of concurrently administered everolimus, gemcitabine and cisplatin in patients with advanced, refractory solid tumors (three-agent MTD).

III. To describe the toxicity of the two treatment combinations. IV. To describe any evidence of the antitumor activity of the two treatment combinations.

  1. To obtain pilot data on toxicity and efficacy outcome of everolimus, gemcitabine and cisplatin in patients with cholangiocarcinoma or gallbladder carcinoma. (Cohort III)

OUTLINE: This is a dose-escalation study of gemcitabine hydrochloride and everolimus.

COHORT I: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8 and everolimus orally (PO) once daily or 3 times weekly.

COHORT II: Patients receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 1 hour on days 1 and 8 and everolimus PO once daily or 3 times weekly.

COHORT III: Patients receive treatment as in cohort II.

Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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

What participants receive

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

  • everolimusDrug

    Also called 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001

    Given PO

  • gemcitabine hydrochlorideDrug

    Also called dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

    Given IV

  • cisplatinDrug

    Also called CACP, CDDP, CPDD, DDP

    Given IV

Study groups in NCT00949949
Study groupRoleWhat they receive
Cohort I (everolimus and gemcitabine hydrochloride)ExperimentalPatients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and everolimus PO once daily or 3 times weekly.
Receives: Drug: everolimus; Drug: gemcitabine hydrochloride
Cohort II (everolimus, gemcitabine hydrochloride, cisplatin)ExperimentalPatients receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 1 hour on days 1 and 8 and everolimus PO once daily or 3 times weekly.
Receives: Drug: everolimus; Drug: gemcitabine hydrochloride; Drug: cisplatin
Cohort III (MTD)ExperimentalPatients receive treatment as in cohort II.
Receives: Drug: everolimus; Drug: gemcitabine hydrochloride; Drug: cisplatin

What is being measured

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

  1. Adverse events profile

    Tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion.

    Measured: Up to 3 months post-treatment

  2. Toxicity profile per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0

    Defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. Non-hematologic toxicities will be evaluated via the ordinal Common Toxicity Criteria (CTC) standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

    Measured: Up to 3 months post-treatment

  3. MTD of the combination of everolimus, gemcitabine hydrochloride, and cisplatin

    Toxicity assessed by NCI CTCAE v3.0.

    Measured: 3 weeks

Secondary outcomes (2)

  1. Response profile

    Best response is defined to be the best objective status recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria will be used for tumor evaluation. Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group).

    Measured: Up to 5 years

  2. Timed endpoints

    The data on time-related variables will be summarized descriptively. These include time until any treatment related toxicity, time until treatment related grade 3+ toxicity, time until hematologic nadirs (white blood cells [WBC], ANC, platelets), time to progression and time to treatment failure, where time to treatment failure is defined as the time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient.

    Measured: Up to 5 years

Timeline

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

  1. First posted31 Jul 2009 (estimated)
  2. Study startSep 2009
  3. Primary completionJul 2014
  4. Study completionJul 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 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00949949
Sponsor's protocol ID
MC0812
Other IDs
NCI-2009-01151, 09-000809, MC0812, P30CA015083
Status last verified
Jan 2017
First submitted
30 Jul 2009
Last updated
12 Jan 2017
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing everolimus, gemcitabine hydrochloride and cisplatin in people with Cholangiocarcinoma of the Gallbladder and Localized Gallbladder Cancer, 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 17 inclusion and 26 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 12 Jan 2017. 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?

Adverse events profile (time frame: Up to 3 months post-treatment). The study lists 3 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 NCT00949949.

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 12 Jan 2017.

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