Paclitaxel Followed by FEC Versus Paclitaxel and RAD001 Followed by FEC In Women With Breast Cancer

NCT00499603 | Unknown Phase 2 Results DMC

• 4 other identifiers: 2006-0790NCI-2012-015141K23CA121994-11K23CA121994
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research is to learn if RAD001 given in combination with chemotherapy will turn off the signaling pathway (a chain of information that tells cancer cells to grow quickly) and make the chemotherapies given on this study more effective. Primary Objective · To determine if the addition of an mTOR inhibitor to standard neoadjuvant chemotherapy in patients with triple receptor-negative breast cancer causes molecular changes (inhibition/activation) of the PI3K/PTEN/AKT pathway. Secondary Objectives

• To evaluate pathologic complete response (pCR) rates for each treatment group.
• To evaluate the relationship between pCR and the molecular changes (inhibition/activation) of the PI13K/PTEN/AKT pathway in each treatment group.
• To evaluate overall response rates (ORR) for each treatment group.
• To assess the toxicity of both regimens and to evaluate the relationship of toxicities with PI3K/PTEN/AKT pathway status.

Conditions

Breast Cancer

Keywords

Breast Cancer; ER negative; PR negative; HER2neu negative; Tumor Triple Negative Receptors; Paclitaxel; Taxol; RAD001; FEC; 5-Fluorouracil; 5-FU; Adrucil; Efudex; Epirubicin; Cyclophosphamide

Outcome Measures

Primary Outcomes (1)

• Number Participants With Inhibition of PI3K/PTEN/AKT Pathway at 48 Hours

  Number of participants with inhibition of the PI3K/PTEN/AKT pathway at 48 hours after the start of treatment, regardless of the status of the pathway at the time of randomization. Molecular changes (inhibition/activation) of the PI3K/PTEN/AKT pathway evaluated using reverse phase protein arrays (RPPA) where fine-needle aspirations (FNAs) from the primary breast cancer obtained pretreatment, and at 48 hours. Bioinformatics cluster analysis of arrays used to define molecular changes as inhibition or activation where pathways called 'active' with presence of 2 or more phosphorilated pathway proteins (pAKT, pmTOR, pGSK3, pS6K1, pS6), and 'inhibited' with one or none phosphorilated pathway proteins present.

  48 hours after start of treatment

Secondary Outcomes (2)

• Participant Responses Per Treatment Arm at 12 Weeks

  12 weeks

• Participant Responses Per Treatment Arm at 24 Weeks

  24 weeks

Study Arms (2)

Paclitaxel + FEC

EXPERIMENTAL

Paclitaxel 80 mg/m\^2 intravenously (IV) on day 1(+/- 2 days) of each week, followed by four cycles of combination 5-Fluorouracil at 500 mg/m\^2, Epirubicin at 100 mg/m\^2 and Cyclophosphamide at 500 mg/m\^2 (FEC) on day 1 every 3 weeks (+/- 7 days).

Drug: Paclitaxel; Drug: 5-Fluorouracil; Drug: Epirubicin; Drug: Cyclophosphamide

Paclitaxel + RAD001 + FEC

EXPERIMENTAL

Paclitaxel + RAD001 Followed by FEC (5-Fluorouracil + Epirubicin + Cyclophosphamide)

Drug: Paclitaxel; Drug: 5-Fluorouracil; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: RAD001

Interventions

Paclitaxel DRUG

80 mg/m\^2 by vein once weekly over 1 hour on day 1(+/- 2 days) each week for 3 weeks and for 12 cycles.

Also known as: Taxol

Paclitaxel + FEC; Paclitaxel + RAD001 + FEC

5-Fluorouracil DRUG

500 mg/m\^2 by vein on day 1 every 3 weeks (+/- 7 days) for 4 cycles.

Also known as: 5-FU, Adrucil, Efudex

Paclitaxel + FEC; Paclitaxel + RAD001 + FEC

Epirubicin DRUG

100 mg/m\^2 by vein on day 1 every 3 weeks (+/- 7 days) for 4 cycles.

Paclitaxel + FEC; Paclitaxel + RAD001 + FEC

Cyclophosphamide DRUG

500 mg/m\^2 by vein on day 1 every 3 weeks (+/- 7 days) for 4 cycles.

Also known as: Cytoxan®, Neosar®

Paclitaxel + FEC; Paclitaxel + RAD001 + FEC

RAD001 DRUG

30 mg by mouth weekly on Days 1, 8, \& 15 for 12 cycles.

Paclitaxel + RAD001 + FEC

Eligibility Criteria

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

You may qualify if:

• Patients with histologic confirmation of invasive ER/PR and HER2/neu-negative breast carcinoma. Immunohistochemistry (IHC) must be used for ER/PR evaluation and IHC or FISH for determination of HER2/neu. ER/PR will be considered negative if equal or lower than 5% IHC staining and HER2/neu will be considered negative if IHC of 0% or negative FISH.
• Patients must have intact primary tumors.
• Age equal or greater than 18 years
• Patients should have stage IIA (T1N1) to IIIC non inflammatory breast cancer.
• Patients with bilateral breast cancers are eligible.
• Patients should have a Karnofsky performance scale of =/\> 70%.
• Patients must have clinically measurable disease to be treated in the neoadjuvant setting. This includes patients with a non-palpable primary tumor who have histologically proven lymph node involvement that is clinically palpable and measurable by ultrasound.
• Patients should have adequate bone marrow function, as defined by peripheral granulocyte count of \>/= 1500/mm3, and a platelet count \>/= 100000/ mm3.
• Patients must have adequate liver function with a bilirubin within normal laboratory values. Alkaline phosphatase and transaminases (ALT and AST) may be up to 1.5 x upper limit of normal (ULN) of the institution.
• Patients should have adequate renal function with creatinine levels 2.0 mg/dL or lower
• Patients should have a normal left ventricular ejection fraction of =/\> 50%.
• Negative serum pregnancy test for a woman of childbearing potential.
• Women of childbearing potential (WOCBP) must use a reliable and appropriate contraceptive method during the study and 6 months after chemotherapy is completed. WOCBP are women who are not menopausal for 12 months or had no previous surgical sterilization.
• Patients must agree to have study biopsies.
• Patients must sign an informed consent indicating that they are aware of the investigational nature of the study, in keeping with institutional policy.

You may not qualify if:

• Patients whose tumors express ER, PR or HER2/neu gene amplification.
• Patients with a history of other invasive malignancies diagnosed and treated within the previous 5 years, except non-melanoma skin cancer and non-invasive cervical cancer
• Patients with an organ allograft or other history of immune compromise
• Prior exposure to mTOR inhibitors
• Hypersensitivity to rapamycin or other similar compounds
• Prior treatment with any investigational drug within the preceding 4 weeks
• Chronic treatment with systemic steroids or another immunosuppressive agent
• A known history of HIV seropositivity
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
• Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin defined as 1 mg a day).
• Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, unstable angina, or congestive heart failure - New York Heart Association Class III or IV, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within six months, chronic liver or renal disease, active upper GI tract ulceration)
• Patients with a pre-existing peripheral neuropathy \> grade 1
• Patients taking medications metabolized by the CYP3A4 subfamily will not be included in this study.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Novartis: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Gonzalez-Angulo AM, Akcakanat A, Liu S, Green MC, Murray JL, Chen H, Palla SL, Koenig KB, Brewster AM, Valero V, Ibrahim NK, Moulder-Thompson S, Litton JK, Tarco E, Moore J, Flores P, Crawford D, Dryden MJ, Symmans WF, Sahin A, Giordano SH, Pusztai L, Do KA, Mills GB, Hortobagyi GN, Meric-Bernstam F. Open-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancerdagger. Ann Oncol. 2014 Jun;25(6):1122-7. doi: 10.1093/annonc/mdu124. Epub 2014 Mar 24.

  PMID: 24669015 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; Fluorouracil; Epirubicin; Cyclophosphamide; Everolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Sirolimus; Macrolides; Lactones

Results Point of Contact

• Title: Clinical Research Operations, Office of VP Clinical Research
• Organization: The University of Texas MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-7734

Study Officials

• Stacy Moulder, M.D.

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2007
• First Posted: July 11, 2007
• Study Start: July 1, 2007
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2017
• Last Updated: November 1, 2016
• Results First Posted: October 31, 2013

Record last verified: 2016-09

Locations

US (1)