Cisplatin and Paclitaxel With or Without Everolimus in Treating Patients With Stage II or Stage III Breast Cancer

NCT00930930 | Completed Phase 2 Results DMC

• 4 other identifiers: VICC BRE 0904P30CA068485VU-VICC-BRE-0904IRB# 090291
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 8

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 chemotherapy together with everolimus before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether cisplatin and paclitaxel are more effective when given together with or without everolimus in treating patients with breast cancer. PURPOSE: This randomized phase II trial is studying how well cisplatin and paclitaxel work when given together with or without everolimus in treating patients with stage II or stage III breast cancer.

Conditions

Breast Cancer

Keywords

triple-negative breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; male breast cancer

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Pathological Complete Response

  Pathological complete response is defined as no residual tumor on histopathological analysis of both breast and axillary contents.

  at time of surgery, week 15-18

Secondary Outcomes (3)

• Number of Patients That Underwent Breast Conservation Surgery

  at the time of surgery, week 15-18

• Clinical Tumor Response to Neoadjuvant Therapy as Measured by Ultrasound Immediately Before Surgery

  After treatment, week 12-15

• Number of Patients With Each Worst-grade Toxicity Response

  week 12

Other Outcomes (2)

• Therapy-mediated Changes in Cell Cycle Position, Proliferation, and Apoptosis as Well as Status, Levels, and Phosphorylation State of p53, p73, and p63 and Select p53 Family Target Genes

  Before treatment, on day 3-5 of week 1, and at week 12

• Ability of p63 and p73 Gene Signatures to Predict Patient Response

  Before treatment, on day 3-5 of week 1, and at week 12

Study Arms (2)

Cisplatin and Paclitaxel + RAD001

EXPERIMENTAL

Cisplatin 25 mg/m2 IV weekly + RAD001 5 mg PO daily for 1 week followed by Cisplatin 25 mg/m2 IV + Paclitaxel 80 mg/m2 IV weekly + RAD001 5 mg PO daily for 11 weeks

Drug: cisplatin; Drug: everolimus; Drug: paclitaxel; Procedure: Venous blood draw

Cisplatin and Paclitaxel + Placebo

ACTIVE COMPARATOR

Cisplatin 25 mg/m2 IV weekly + placebo PO daily for 1 week followed by Cisplatin 25 mg/m2 IV + Paclitaxel 80 mg/m2 IV weekly + placebo PO daily for 11 weeks

Drug: cisplatin; Drug: paclitaxel; Other: placebo; Procedure: Venous blood draw

Interventions

cisplatin DRUG

Given IV

Cisplatin and Paclitaxel + Placebo; Cisplatin and Paclitaxel + RAD001

everolimus DRUG

Given orally

Cisplatin and Paclitaxel + RAD001

paclitaxel DRUG

Given IV

Cisplatin and Paclitaxel + Placebo; Cisplatin and Paclitaxel + RAD001

placebo OTHER

Given orally

Cisplatin and Paclitaxel + Placebo

Venous blood draw PROCEDURE

Venous blood (2-3 tablespoons) will be taken for germline DNA analysis to complement the correlative studies in the tumor tissue. Blood can be drawn at any time prior, during, or after completion of study treatment

Cisplatin and Paclitaxel + Placebo; Cisplatin and Paclitaxel + RAD001

Eligibility Criteria

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

You may qualify if:

• Patients must provide informed written consent.
• Patient must be ≥ 18 years of age.
• ECOG performance status 0-1.
• Clinical stage II or stage III triple-negative (ER and/or PR no staining or weak staining in less than or equal to 10% cells by immunohistochemistry \[IHC\] and HER2-negative by Herceptest \[0, 1+\] or FISH) invasive mammary carcinoma, confirmed by histological analysis.
• Patients who have measurable\* residual tumor at the primary site
• \*Measurable disease: any mass that can be reproducibly measured by physical examination, mammogram, and/or ultrasound and can be accurately measured in at least one dimension (longest diameter to be recorded) as 10 mm (1 cm), either in the breast or axillary lymph nodes.
• Available core biopsies from the time of diagnosis. Fresh tissue must be obtainable at baseline or fresh tissue biopsy prior to treatment initiation.
• Patients who will undergo surgical treatment with either segmental resection or total mastectomy.
• Patients must have adequate hematologic, hepatic, and renal function. All tests must be obtained less than 4 weeks from study entry. This includes:
• ANC \>/=1500/mm3
• Platelet count \>/=100,000/mm3
• Creatinine \</=1.5X upper limits of normal
• Bilirubin, SGOT, SGPT \</=1.5X upper limits of normal\*
• \* for patients with Gilbert"s syndrome, direct bilirubin will be measured instead of total bilirubin.
• The patient must have not had anyprior chemotherapy for primary breast cancer.

You may not qualify if:

• Locally recurrent breast cancer.
• Pregnant or lactating women.
• Evidence of distant metastatic disease (i.e. lung, liver, bone, brain, etc.)
• Use of CYP3A4 modifiers (Appendix A)
• Serious medical illness that in the judgment of the treating physician places the patient at high risk of operative mortality.
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
• History of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinomas are eligible.
• History of hepatitis B or hepatitis C. If patient is judged to be at risk for having had exposure to viral B or C hepatitis (i.e. illicit IV drug use, blood transfusion prior to 1990, body piercing, tattoos, etc.), appropriate testing should be performed (i.e. Hepatitis B surface antigen antibody, and Hepatitis C antibody)
• Active or uncontrolled infection requiring parenteral antibiotics.
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
• Symptomatic neuropathy (≥ grade 2).
• Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, or any other biologic therapy) other than the ones specified in the protocol.
• Concurrent treatment with an investigational agent.
• Used an investigational drug within 15 days or 5 half-lives, whichever is longer, preceding the first dose of randomized therapy.

Sponsors & Collaborators

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

Study Sites (8)

University of Alabama

Birmingham, Alabama, 35249, United States

Location

University of Mississippi Medical Center Research Institute

Jackson, Mississippi, 39213, United States

Location

Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Vanderbilt-Ingram Cancer Center - Cool Springs

Nashville, Tennessee, 37064, United States

Location

MBCCOP - Meharry Medical College - Nashville

Nashville, Tennessee, 37208, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

The Methodist Hospital Research Institute

Houston, Texas, 77030, United States

Location

University of Virginia Health Sciences Center

Charlottesville, Virginia, 22098, United States

Location

Related Publications (1)

• Jovanovic B, Sheng Q, Seitz RS, Lawrence KD, Morris SW, Thomas LR, Hout DR, Schweitzer BL, Guo Y, Pietenpol JA, Lehmann BD. Comparison of triple-negative breast cancer molecular subtyping using RNA from matched fresh-frozen versus formalin-fixed paraffin-embedded tissue. BMC Cancer. 2017 Apr 4;17(1):241. doi: 10.1186/s12885-017-3237-1.

  PMID: 28376728 DERIVED

Related Links

• Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms; Breast Neoplasms, Male

Interventions

Cisplatin; Everolimus; Paclitaxel; Blood Specimen Collection

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; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

The number of participants in each arm will not necessarily coincide with the number of participants affected in the respective arm. Some participants my have more than one event and/or some participants may not have an event at all.

Results Point of Contact

• Title: Dr. Ingrid Mayer
• Organization: Vanderbilt-Ingram Cancer Center

ingrid.mayer@vanderbilt.edu

615-936-2033

Study Officials

• Ingrid Mayer, M.D.

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine; Clinical Director, Breast Cancer Program; Medical Oncologist

Study Record Dates

• First Submitted: July 1, 2009
• First Posted: July 2, 2009
• Study Start: June 1, 2009
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2014
• Last Updated: May 7, 2015
• Results First Posted: May 7, 2015

Record last verified: 2015-05

Locations

US (8)