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Acinar Cell Adenocarcinoma of the PancreasPhase 1NCT01924260

Alisertib and Gemcitabine Hydrochloride in Treating Patients With Solid Tumors or Pancreatic Cancer

A Phase 1 study testing alisertib and gemcitabine in people with Acinar Cell Adenocarcinoma of the Pancreas and Duct Cell Adenocarcinoma of the Pancreas, run by Edward Kim at 1 site 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 alisertib when given together with gemcitabine hydrochloride 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?
alisertib and gemcitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
9 Aug 2013to 8 Feb 2017
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

  • Eligibility for dose escalation cohort: histologically or cytologically confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective
  • Eligibility for the expansion cohort: histologically or cytologically confirmed metastatic or unresectable pancreatic adenocarcinoma for which curative treatment does not exist
  • Zubrod (Eastern Cooperative Oncology Group [ECOG]) performance status 0 - 2
  • Measurable or non-measurable disease. x-rays and/or scans for disease assessment of measurable disease must have been completed within 28 days prior to registration; non-measurable disease must also be assessed within 28 days prior to registration; (expansion - patients must have measurable disease)
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
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  • Total bilirubin within institutional normal limits
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 times institutional upper limit of normal or =< 5 times institutional upper limit of normal in the presence of liver metastases
  • Creatinine =< 1.5 times institutional upper limit of normal OR
  • Creatinine Clearance >= 60ml/min/1.73m^2 measured by 24-hour urine collection
  • Any number of prior chemotherapy regimens; up to two prior chemotherapy regimen in the palliative setting will be allowed in the expansion cohort. Prior gemcitabine-based regimes in the palliative setting are permitted if no evidence of progression on therapy or at least 6 months after discontinuation of gemcitabine based treatment. Prior gemcitabine in the adjuvant setting is permitted if last treatment was greater than 6 months prior to registration
  • Any prior chemotherapy, immunotherapy or targeted therapy must have been completed at least 2 weeks prior to start of this protocol and all side effects (except alopecia, lymphopenia and hyperglycemia) resolved to grade 1 or less; any prior radiation must have been completed at least 2 weeks prior to start of therapy
  • Pregnant or nursing women are ineligible; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
  • Ability to understand and the willingness to sign a written informed consent document
  • Ability to swallow and retain oral medications
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
  • Male subject agrees to use an acceptable method for contraception during the entire study treatment period through 4 months after the last dose of MLN8237; male patients, even if surgically sterilized (ie, status postvasectomy) must agree to practice effective barrier contraception during the entire study treatment period and through four months after the last dose of study drug, or completely abstain from heterosexual intercourse

Who cannot join

  • Prior treatment with Aurora A-targeted agents, including MLN8237
  • History of Gilbert's syndrome
  • Cardiac disease: congestive heart failure > class II New York Heart Association (NYHA); patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
  • Symptomatic or uncontrolled brain metastasis; patients with neurological symptoms must undergo a computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastasis; previously treated brain metastases will be allowed as long as the patient is neurologically stable and is off steroids and anticonvulsants
  • Prior radiation to greater than 25% of the bone marrow or whole pelvis radiation
  • Patients requiring full therapeutic anticoagulation with warfarin are ineligible because therapy on this trial may result in frequent and recurrent thrombocytopenia; full therapeutic anticoagulation with heparin, low molecular weight heparin, or direct factor Xa inhibitor is permitted
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  • Patients with a diagnosis of active human immunodeficiency virus (HIV) infection, on anti-retroviral therapy, or with a cluster of differentiation (CD) 4 count less than 200 are ineligible; testing is not required in the absence of clinical findings or suspicion
  • Patients with a diagnosis of chronic hepatitis B are ineligible
  • Active clinically serious infection > Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or systemic infection requiring IV antibiotic therapy within 14 days preceding the first dose of study drug
  • Serious non-healing wound, ulcer, or bone fracture
  • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug
  • Known or suspected allergy to gemcitabine or MLN8237, or any agent given in the course of this trial
  • Any clinically significant medical or psychiatric condition that would interfere with protocol treatment
  • Prior allogeneic bone marrow or organ transplantation
  • Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen
  • Requirement for constant administration of proton pump inhibitor or H2 antagonist; intermittent uses of antacids or H2 antagonists are allowed
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
  • Female subject is pregnant or breast-feeding; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
  • Patient has received other investigational drugs with 14 days before enrollment
  • Other severe acute or chronic medical or psychiatric condition, including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study
  • Treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort within 14 days prior to the first dose of MLN8237 and during the study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UC Davis Comprehensive Cancer Center

    Sacramento, California, 95817

Other trials in United States

About this study

Official title: Phase I Study of the Combination of MLN8237 and Gemcitabine in Advanced Solid Tumors With Emphasis on Pancreatic Cancer

This phase I trial studies the side effects and the best dose of alisertib when given together with gemcitabine hydrochloride in treating patients with solid tumors or pancreatic cancer that is metastatic or cannot be removed by surgery. Alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving alisertib with gemcitabine hydrochloride may be an effective treatment for solid tumors or pancreatic cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To investigate the feasibility and safety of MLN8237 (alisertib) when given in combination with gemcitabine (gemcitabine hydrochloride) to patients with advanced solid tumors.

SECONDARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of MLN8237 when given in combination with gemcitabine to patients with advanced solid tumors and to recommend a phase II dose for the combination.

II. To obtain preliminary evidence of efficacy as judged by response rate and progression-free survival for this combination.

III. To investigate the pharmacokinetics of MLN8237 given in combination with gemcitabine in an expanded cohort of patients with pancreatic cancer.

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

Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15 and alisertib orally (PO) twice daily (BID) on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Being tested
alisertib, gemcitabine
Medical subject headings
Pancreatic Neoplasms

What participants receive

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

  • alisertibDrug

    Also called Aurora A kinase inhibitor MLN8237, MLN8237

    Given PO

  • gemcitabineDrug

    Also called dFdC, difluorodeoxycytidine hydrochloride, Gemzar

    Given IV

Study groups in NCT01924260
Study groupRoleWhat they receive
Treatment (alisertib, gemcitabine)ExperimentalPatients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: alisertib; Drug: gemcitabine

What is being measured

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

  1. Dose-limiting toxicity (DLT) defined as any related (possibly, probably, or definitely) grade 3 non-hematological toxicity or any attributable grade 4 toxicity graded according to the National Cancer Institute (NCI) CTCAE version 4.0

    Measured: Up to 21 days

Secondary outcomes (4)

  1. Incidence of adverse events graded according to NCI CTCAE version 4.0

    Toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by grade and nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility or outcome. Frequencies will be reported, with exact 95% confidence intervals. Tables will be created to summarize these toxicities and side effects by dose and by course.

    Measured: Up to 30 days after completion of treatment

  2. Response rate according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

    Survival will be summarized with Kaplan-Meier plots to describe the outcome of patients treated on this protocol. Median survival time will be estimated using standard life table methods.

    Measured: Assessed up to 2 years

  3. Progression Free Survival

    Summarized with Kaplan-Meier plots. Median survival time will be estimated using standard life table methods.

    Measured: Assessed up to 2 years

  4. Maximum-tolerated dose (MTD) defined as the maximum dose level at which less than 2 patients experience DLT graded according to NCI CTCAE version 4.0

    Measured: 21 days

Timeline

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

  1. First posted16 Aug 2013 (estimated)
  2. Study start9 Aug 2013
  3. Primary completion8 Feb 2017
  4. Study completion8 Feb 2017

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
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01924260
Sponsor's protocol ID
457403
Other IDs
UCDCC#240, P30CA093373, X14020, NCI-2013-01388
Status last verified
Jul 2022
First submitted
13 Aug 2013
Last updated
2 Aug 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing alisertib and gemcitabine in people with Acinar Cell Adenocarcinoma of the Pancreas and Duct Cell Adenocarcinoma of the Pancreas, run by Edward Kim at 1 site 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 18 inclusion and 21 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 2 Aug 2022. 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 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?

Dose-limiting toxicity (DLT) defined as any related (possibly, probably, or definitely) grade 3 non-hematological toxicity or any attributable grade 4 toxicity graded according to the National Cancer Institute (NCI) CTCAE version 4.0 (time frame: Up to 21 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 NCT01924260.

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 2 Aug 2022.

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