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

NCT01924260 | Completed Phase 1 DMC FDA Drug

• 5 other identifiers: 457403UCDCC#240P30CA093373X14020NCI-2013-01388
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (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

  Up to 21 days

Secondary Outcomes (4)

• Incidence of adverse events graded according to NCI CTCAE version 4.0

  Up to 30 days after completion of treatment

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

  Assessed up to 2 years

• Progression Free Survival

  Assessed up to 2 years

• 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

  21 days

Study Arms (1)

Treatment (alisertib, gemcitabine)

EXPERIMENTAL

Patients 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.

Drug: alisertib; Drug: gemcitabine

Interventions

alisertib DRUG

Given PO

Also known as: Aurora A kinase inhibitor MLN8237, MLN8237

Treatment (alisertib, gemcitabine)

gemcitabine DRUG

Given IV

Also known as: dFdC, difluorodeoxycytidine hydrochloride, Gemzar

Treatment (alisertib, gemcitabine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Edward Kim: lead
• National Cancer Institute (NCI): collaborator
• Takeda: collaborator

Study Sites (1)

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Related Links

• University of California Davis Comprehensive Cancer Center

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

MLN 8237; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Karen Kelly

  UC Davis Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 13, 2013
• First Posted: August 16, 2013
• Study Start: August 9, 2013
• Primary Completion: February 8, 2017
• Study Completion: February 8, 2017
• Last Updated: August 2, 2022

Record last verified: 2022-07

Locations

US (1)