Cisplatin, Paclitaxel, and Everolimus in Treating Patients With Metastatic Breast Cancer

NCT ID: NCT01031446

Last Updated: 2018-08-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2017-08-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving cisplatin and paclitaxel together with everolimus may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects of giving cisplatin and paclitaxel together with everolimus and to see how well it works in treating patients with metastatic breast cancer.

Detailed Description

OBJECTIVES:

Primary

• Safety profile of cisplatin, paclitaxel, and everolimus (RAD001) in patients with metastatic breast cancer. (Phase I)
• Progression-free survival (Phase II)

Secondary

• Overall response rate
• Time to progression
• Number of patients with worst-grade toxicities Tertiary
• To determine p53, p63, p73, and phosphatase and tensin homolog (PTEN) levels by immunohistochemistry (IHC).
• To screen for exon 9 (E542K and E545K), exon 20 (H1047R), and phosphatidylinositol 3-kinase (PI3K) (p110α) mutations in DNA extracted from paraffin blocks.
• To correlate IHC results with clinical outcome and with the different subtypes of breast cancer determined by molecular classification (basal-type vs luminal A vs luminal B) based on microarrays of RNA extracted from formalin-fixed paraffin-embedded blocks.
• To generate microarrays of RNA extracted from fresh-frozen core biopsies (when available) to identify a pretreatment gene signature that mirrors the established p63 and p73 gene signatures that predict response to treatment.

OUTLINE: This is a multicenter study.

Patients receive oral everolimus once daily on days 1-28 and cisplatin IV over 1 hour and paclitaxel IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Tumor tissue samples are collected at baseline for correlative studies.

After completion of study treatment, patients are followed up at 4 weeks.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Group Type: EXPERIMENTAL

cisplatin

Intervention Type: DRUG

Given through a vein in the arm 1 time a week for 3 weeks, then a one week break and then begin the process again.

everolimus

Intervention Type: DRUG

Taken daily by mouth.

paclitaxel

Intervention Type: DRUG

Given through a vein in the arm 1 time a week for 3 weeks, then a one week break and then begin the process again.

laboratory biomarker analysis

Intervention Type: OTHER

Blood collection

Interventions

cisplatin

Given through a vein in the arm 1 time a week for 3 weeks, then a one week break and then begin the process again.

Intervention Type: DRUG

everolimus

Taken daily by mouth.

Intervention Type: DRUG

paclitaxel

Given through a vein in the arm 1 time a week for 3 weeks, then a one week break and then begin the process again.

Intervention Type: DRUG

laboratory biomarker analysis

Blood collection

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patients with asymptomatic brain metastases are eligible provided they are not taking prophylactic anticonvulsants that are CYP3A4 modifiers

PATIENT CHARACTERISTICS:

• Pre- or post-menopausal
• European Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy ≥ 6 months
• Absolute neutrophil count (ANC) ≥ 1,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 times ULN (≤ 3 times ULN in the presence of liver metastasis)

• Direct bilirubin will be measured in patients with Gilbert syndrome
• serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) ≤ 1.5 times ULN (≤ 3 times ULN in the presence of liver metastasis)
• Alkaline phosphatase ≤ 3 times ULN (in the presence of liver metastasis)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 3 months after completion of study treatment
• Able to swallow and retain oral medication
• No malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel
• No concurrent uncontrolled illness including, but not limited to, any of the following:

• Ongoing or active infection requiring parenteral antibiotics
• Impaired lung function (chronic obstructive pulmonary disease or lung conditions requiring oxygen therapy)
• New York Heart Association class III-IV congestive heart failure
• Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within the past 6 months
• Uncontrolled hypertension (systolic BP > 180 mm Hg or diastolic BP > 100 mm Hg, found on 2 consecutive measurements separated by a 1-week period and despite adequate medical support)
• Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment [grade 3 according to NCI Common Toxicity Criteria for Adverse Events v3.0])
• Uncontrolled diabetes (hyperosmolar state, ketoacidosis, etc.)
• Psychiatric illness or social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary
• No symptomatic neuropathy ≥ grade 2
• No other invasive cancer within the past 5 years except for completely resected basal cell or squamous cell carcinoma of the skin or successfully treated cervical carcinoma in situ
• No hypersensitivity to paclitaxel or drugs using the vehicle Cremophor, Chinese hamster ovary cell products, or other recombinant human antibodies
• No history of hepatitis B or C

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• Prior total cumulative life-time dose of doxorubicin ≤ 360 mg/m^2 or epirubicin ≤ 640 mg/m^2
• No more than 4 prior chemotherapy treatments in the metastatic setting (not including endocrine therapy or single-agent biologic therapy)
• At least 2 weeks since prior investigational drugs
• At least 14 days since prior and no concurrent herbal or dietary supplements
• At least 14 days since prior and no concurrent CYP3A4 inducers
• At least 7 days since prior and no concurrent CYP3A4 inhibitors
• Concurrent radiotherapy to painful bone metastases or areas of impending bone fracture allowed provided radiotherapy is initiated before study entry
• No other concurrent anticancer therapy (chemotherapy, radiotherapy, surgery, immunotherapy, hormonal therapy, biologic therapy)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Ingrid Mayer, MD

Assistant Professor of Medicine; Clinical Director, Breast Cancer Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ingrid Mayer, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt-Ingram Cancer Center

Locations

Erlanger Cancer Center at Erlanger Hospital - Baroness

Chattanooga, Tennessee, United States

West Tennessee Cancer Center at Jackson-Madison County General Hospital

Jackson, Tennessee, United States

Baptist Regional Cancer Center at Baptist Riverside

Knoxville, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

P30CA068485

Identifier Type: NIH

Identifier Source: secondary_id

View Link

VU-VICC-BRE-0949

Identifier Type: -

Identifier Source: secondary_id

IRB# 090673

Identifier Type: -

Identifier Source: secondary_id

VICC BRE 0949

Identifier Type: -

Identifier Source: org_study_id