Carboplatin and Nab-Paclitaxel With or Without Vorinostat in Treating Women With Newly Diagnosed Operable Breast Cancer

NCT00616967 | Active Not Recruiting Phase 2 Results

• 6 other identifiers: J0785P30CA006973NA_00012756JHOC-SKCCC-J0785JHOC-J0785CDR0000586335
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 5

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vorinostat may also help carboplatin and paclitaxel albumin-stabilized nanoparticle formulation work better by making tumor cells more sensitive to the drugs. Giving chemotherapy with or without vorinostat before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This randomized phase II trial is studying how well giving carboplatin together with paclitaxel albumin-stabilized nanoparticle formulation works with or without vorinostat in treating women with breast cancer that can be removed by surgery.

Conditions

Breast Cancer

Keywords

stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; ductal breast carcinoma; lobular breast carcinoma

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR) Rate

  The primary end point was pCR, defined as no viable invasive cancer in breast and axilla. All other cases were defined as non-pCR. The pCR rate was determined in each arm separately by performing an intent-to-treat (ITT) analysis of all randomized patients. Patients with unknown pCR status were considered non-responders. Computation of associated 90% confidence intervals did not account for the sequential design.

  Time of breast cancer surgery

Secondary Outcomes (10)

• Safety as Measured by Number of Participants Who Experience Adverse Events

  up to 30 days post-treatment

• Number of Participants With Clinical Complete Response (cCR)

  12 weeks

• Change in Standard Uptake Value (SULmax) From Baseline to Day 15 on FDG-PET

  Baseline and day 15

• Absolute Change From Baseline in Ki-67

  Change from baseline to Cycle 1-Day 15

• Change in Cumulative Methylation Index (CMI)

  Change from baseline to Day 15

Study Arms (2)

Arm I

ACTIVE COMPARATOR

Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.

Drug: carboplatin; Drug: paclitaxel albumin-stabilized nanoparticle formulation; Other: placebo

Arm II

EXPERIMENTAL

Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.

Drug: carboplatin; Drug: paclitaxel albumin-stabilized nanoparticle formulation; Drug: vorinostat

Interventions

carboplatin DRUG

Given IV

Also known as: Paraplatin

Arm I; Arm II

vorinostat DRUG

Given orally

Also known as: Zolinza

Arm II

paclitaxel albumin-stabilized nanoparticle formulation DRUG

Given IV

Also known as: Abraxane, nab-Paclitaxel

Arm I; Arm II

placebo OTHER

Given orally

Arm I

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed infiltrating ductal breast cancer by core needle biopsy * Mixed ductal and lobular disease allowed * Infiltrating lobular cancer allowed in the run-in portion only * Unresected, clinically measurable disease, meeting 1 of the following clinical staging criteria: * T2, T3, or T4 lesion, any N, M0 * T1c, N1-3,M0 * Patients with skin metastases to the ipsilateral breast for whom chemotherapy is planned prior to definitive surgery are eligible for the primary study portion * HER2-negative disease * Hormone receptor status\* meeting 1 of the following criteria: * Estrogen receptor (ER)-negative and progesterone receptor (PR)-negative * ER-positive (grade II or III) and PR-positive or PR-negative NOTE: \*Any ER or PR status for the run-in portion PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * Menopausal status not specified * ANC ≥ 1,500/mm³ * Platelet count ≥ 150,000/mm³ * Hemoglobin ≥ 9 g/dL * Creatinine ≤ 1.5 times the upper limit of normal (ULN) * Creatinine clearance ≥ 50 mL/min * Total bilirubin normal * AST(SGOT) and ALT(SGPT) ≤ 2.5 times (ULN) * alkaline phosphatase ≤ 2.5 times ULN * PT such that INR ≤ 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and PTT ≤ ULN * Adequate cardiac function defined as no evidence of PR prolongation or AV block on baseline electrocardiogram (ECG) * Willing to use effective, non-hormonal contraception while on treatment and for at least 3 months thereafter * Not pregnant or nursing * No pre-existing peripheral neuropathy ≥ grade 2 * No history of severe hypersensitivity reaction to any drug formulated with polysorbate 80 or to E. coli-derived products * No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat * No medical condition which, in the opinion of the investigator, puts the patient at risk of potentially serious complications while on this therapy PRIOR CONCURRENT THERAPY: * At least 4 weeks since prior valproic acid or other histone deacetylase inhibitor * No prior chemotherapy, radiotherapy, or endocrine therapy for this cancer * Prior tamoxifen or raloxifene or another agent for prevention of breast cancer allowed as long as the patient has discontinued the treatment ≥ 1 month prior to baseline study biopsy * No systemic treatment for prior cancer within the past 5 years (primary study portion) * No prior or ongoing systemic treatment for this cancer (primary study portion) * No concurrent combination antiretroviral therapy for HIV-positive patients * No other concurrent histone deacetylase inhibitor * No other concurrent chemotherapy, antiestrogen therapy, radiotherapy, or other investigational systemic therapy * No other concurrent biologic therapy * No other concurrent investigational drugs

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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

University of Alabama Comprehensive Cancer Center

Birmingham, Alabama, 35249, United States

Location

Indiana University Purdue University of Indianapolis

Indianapolis, Indiana, 46202, United States

Location

Anne Arundel Health System

Annapolis, Maryland, 21401, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Related Publications (2)

• Connolly RM, Leal JP, Goetz MP, Zhang Z, Zhou XC, Jacobs LK, Mhlanga J, O JH, Carpenter J, Storniolo AM, Watkins S, Fetting JH, Miller RS, Sideras K, Jeter SC, Walsh B, Powers P, Zorzi J, Boughey JC, Davidson NE, Carey LA, Wolff AC, Khouri N, Gabrielson E, Wahl RL, Stearns V. TBCRC 008: early change in 18F-FDG uptake on PET predicts response to preoperative systemic therapy in human epidermal growth factor receptor 2-negative primary operable breast cancer. J Nucl Med. 2015 Jan;56(1):31-7. doi: 10.2967/jnumed.114.144741. Epub 2014 Dec 4.

  PMID: 25476537 RESULT

• Connolly RM, Fackler MJ, Zhang Z, Zhou XC, Goetz MP, Boughey JC, Walsh B, Carpenter JT, Storniolo AM, Watkins SP, Gabrielson EW, Stearns V, Sukumar S. Tumor and serum DNA methylation in women receiving preoperative chemotherapy with or without vorinostat in TBCRC008. Breast Cancer Res Treat. 2018 Jan;167(1):107-116. doi: 10.1007/s10549-017-4503-2. Epub 2017 Sep 16.

  PMID: 28918548 RESULT

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular

Interventions

Carboplatin; Taxes; Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel; Vorinostat

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Ductal; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Limitations and Caveats

A proportion of women received additional preoperative chemotherapy after study treatment,complicating the evaluation of primary endpoint and role of FDG-PET in predicting response. Limited matched samples for Ki67 analysis.

Results Point of Contact

• Title: Dr. Vered Stearns
• Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

vstearn1@jhmi.edu

443-287-6489

Study Officials

• Vered Stearns, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

Publication Agreements

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

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: SPONSOR

Study Record Dates

• First Submitted: February 14, 2008
• First Posted: February 15, 2008
• Study Start: May 1, 2008
• Primary Completion: June 1, 2014
• Study Completion (Estimated): February 1, 2027
• Last Updated: March 5, 2026
• Results First Posted: July 16, 2014

Record last verified: 2026-02

Locations

US (5)