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

NCT00949949 | Completed Phase 1 DMC

• 4 other identifiers: MC0812NCI-2009-0115109-000809P30CA015083
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 3

Brief 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. 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.

Conditions

Cholangiocarcinoma of the Gallbladder; Localized Gallbladder Cancer; Unresectable Gallbladder Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (3)

• 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.

  Up to 3 months post-treatment

• 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.

  Up to 3 months post-treatment

• MTD of the combination of everolimus, gemcitabine hydrochloride, and cisplatin

  Toxicity assessed by NCI CTCAE v3.0.

  3 weeks

Secondary Outcomes (2)

• Response profile

  Up to 5 years

• Timed endpoints

  Up to 5 years

Study Arms (3)

Cohort I (everolimus and gemcitabine hydrochloride)

EXPERIMENTAL

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

Drug: everolimus; Drug: gemcitabine hydrochloride

Cohort II (everolimus, gemcitabine hydrochloride, cisplatin)

EXPERIMENTAL

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.

Drug: everolimus; Drug: gemcitabine hydrochloride; Drug: cisplatin

Cohort III (MTD)

EXPERIMENTAL

Patients receive treatment as in cohort II.

Drug: everolimus; Drug: gemcitabine hydrochloride; Drug: cisplatin

Interventions

everolimus DRUG

Given PO

Also known as: 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001

Cohort I (everolimus and gemcitabine hydrochloride); Cohort II (everolimus, gemcitabine hydrochloride, cisplatin); Cohort III (MTD)

gemcitabine hydrochloride DRUG

Given IV

Also known as: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

Cohort I (everolimus and gemcitabine hydrochloride); Cohort II (everolimus, gemcitabine hydrochloride, cisplatin); Cohort III (MTD)

cisplatin DRUG

Given IV

Also known as: CACP, CDDP, CPDD, DDP

Cohort II (everolimus, gemcitabine hydrochloride, cisplatin); Cohort III (MTD)

Eligibility Criteria

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

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Interventions

Everolimus; Gemcitabine; Cisplatin

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Brian Costello

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2009
• First Posted: July 31, 2009
• Study Start: September 1, 2009
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: January 12, 2017

Record last verified: 2017-01

Locations

US (3)