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

NCT01031446 | Completed Phase 1 Results DMC

• 4 other identifiers: VICC BRE 0949P30CA068485VU-VICC-BRE-0949IRB# 090673
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 4

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.

Conditions

Breast Cancer

Keywords

stage IV breast cancer; Human epidermal growth factor (HER2)-negative breast cancer; triple-negative breast cancer; hormone-resistant breast cancer

Outcome Measures

Primary Outcomes (3)

• Maximum Feasible Dose in Milligrams Per Meter Squared of Body Surface Area (mg/m2) of Cisplatin and Paclitaxel for Women With Metastatic Breast Cancer

  The recommended dose for the Phase II trial will be the most prevalent dose delivered per week in Phase I that allows for safe and feasible administration of the medications.The maximum tolerated dose (MTD) is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count \[ANC\] \< 0.5 x 10 9/L for \> 5 days), febrile neutropenia (ANC \< 1.0 x 10 0/L with fever \> 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia \< 25 x 10 9/L or CTC Grade 3 \< 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy.

  at 8 weeks

• Maximum Feasible Dose in mg of RAD001 (Everolimus)for Women With Metastatic Breast Cancer

  The recommended dose for the Phase II trial will be the most prevalent dose delivered per day in Phase I that allows for safe and feasible administration the medication. The MTD is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count \[ANC\] \< 0.5 x 10 9/L for \> 5 days), febrile neutropenia (ANC \< 1.0 x 10 0/L with fever \> 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia \< 25 x 10 9/L or CTC Grade 3 \< 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy

  at 8 weeks

• Patients With Progression-free Survival

  Patients who had not experienced disease progression and who were alive at 6 months after study entry

  at 6 months

Secondary Outcomes (3)

• Patients With Overall Response

  every 12 weeks

• Time to Progression

  Up to 64 weeks

• Time to Progression in Patients With Metastatic Basal-like Breast Cancer.

  Up to 64 weeks

Study Arms (1)

Treatment

EXPERIMENTAL

Drug: cisplatin; Drug: everolimus; Drug: paclitaxel; Other: laboratory biomarker analysis

Interventions

cisplatin 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.

Treatment

everolimus DRUG

Taken daily by mouth.

Treatment

paclitaxel 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.

Treatment

laboratory biomarker analysis OTHER

Blood collection

Treatment

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed invasive mammary carcinoma * Stage IV disease * Basal-like disease (triple-negative, hormone-refractory, HER2-negative) * No locally recurrent breast cancer * No symptomatic brain metastases * Patients with a history of brain metastases are eligible provided they are clinically stable for \> 3 weeks after completion of radiotherapy and are not taking steroids or therapeutic anticonvulsants that are cytochrome P450 3A4 (CYP3A4) modifiers * 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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Erlanger Cancer Center at Erlanger Hospital - Baroness

Chattanooga, Tennessee, 37403, United States

Location

West Tennessee Cancer Center at Jackson-Madison County General Hospital

Jackson, Tennessee, 38301, United States

Location

Baptist Regional Cancer Center at Baptist Riverside

Knoxville, Tennessee, 37901, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Cisplatin; Everolimus; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Sirolimus; Macrolides; Lactones; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Limitations and Caveats

All patients began at the same dose level of the study drugs with no de-escalation of dose, thus results were combined for outcomes measures 3, 4, 5, and 6 for Phase II.

Results Point of Contact

• Title: Ingrid A. Mayer, MD
• Organization: Vanderbilt-Ingram Cancer Center

ingrid.mayer@vanderbilt.edu

615-936-2033

Study Officials

• Ingrid Mayer, MD

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine; Clinical Director, Breast Cancer Program

Study Record Dates

• First Submitted: December 11, 2009
• First Posted: December 14, 2009
• Study Start: October 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: August 1, 2017
• Last Updated: August 31, 2018
• Results First Posted: March 11, 2013

Record last verified: 2018-08

Locations

US (4)