Neoadjuvant Study of Two Platinum Regimens in Triple Negative Breast Cancer

NCT ID: NCT02413320

Last Updated: 2021-05-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2020-02-01

Brief Summary

Evaluate if the two carboplatin containing chemotherapy regimens will reduce the growth of breast cancer cells in women with Stage I, II, or III triple negative breast cancer.

Detailed Description

Sporadic and germline BRCA mutation associated triple-negative breast cancer share several pathological and molecular similarities which have led to the exploration of DNA damaging agents like platinum compounds in patients with triple-negative breast cancer. Recent studies demonstrate that addition of neoadjuvant carboplatin to doxorubicin/cyclophosphamide/taxane-based chemotherapy improves pathological complete response in patients with stage I-III triple-negative breast cancer but also increase toxicity.

A recent study reported encouraging pathological complete response rates with a non-anthracycline carboplatin plus docetaxel neoadjuvant chemotherapy regimen in a cohort of 49 triple negative breast cancer patients. This chemotherapy regimen of carboplatin plus docetaxel yielded an overall pathological complete response rate of 65% in unselected triple-negative breast cancer with pathological complete response rates of 61% in sporadic and 77% in germline BRCA-associated triple-negative breast cancer. The chemotherapy regimen of carboplatin/docetaxel is well tolerated and should be studied further and compared with regimens that add carboplatin to the standard anthracycline/taxane containing regimens.

This is the basis for the proposed randomized neoadjuvant phase II study to further estimate and compare pathological complete response rates of carboplatin plus docetaxel x 6 cycles to carboplatin plus paclitaxel x 4 cycles followed by doxorubicin plus cyclophosphamide x 4 cycles in stage I-III triple negative-breast cancer.

Conditions

Triple-negative Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carboplatin + Paclitaxel then Doxorubicin + Cyclophosphamide

Paclitaxel (80mg/m2) given IV every week x12 weeks and Carboplatin (AUC 6) given IV every 21 days x 4 cycles, followed by Doxorubicin (60mg/m2) given IV and Cyclophosphamide (600mg/m2) given IV every 14 days X 4 cycles

Group Type: ACTIVE_COMPARATOR

Paclitaxel

Intervention Type: DRUG

Carboplatin

Intervention Type: DRUG

Doxorubicin

Intervention Type: DRUG

Cyclophosphamide

Intervention Type: DRUG

Carboplatin + Docetaxel

Carboplatin (AUC 6) given IV and Docetaxel (75mg/m2) given IV every 21 days x 6 cycles

Group Type: ACTIVE_COMPARATOR

Carboplatin

Intervention Type: DRUG

Docetaxel

Intervention Type: DRUG

Interventions

Paclitaxel

Intervention Type: DRUG

Carboplatin

Intervention Type: DRUG

Doxorubicin

Intervention Type: DRUG

Cyclophosphamide

Intervention Type: DRUG

Docetaxel

Intervention Type: DRUG

Other Intervention Names

taxol; paraplatin; adriamycin; cytoxin, procytox; taxotere

Eligibility Criteria

Inclusion Criteria

• Patients with newly diagnosed stage I (T>1cm), II or III triple negative breast cancer who have not had definitive breast surgery or received systemic chemotherapy
• The invasive tumor must be hormone receptor-poor, defined as both estrogen receptor and progesterone receptor staining present in ≤ 10% of invasive cancer cells by Immunohistochemistry.
• HER- 2 negativity will be based on the current ASCO-CAP guidelines for HER testing
• No prior chemotherapy, endocrine therapy or radiation therapy with therapeutic intent for this cancer
• Female subjects age 18 - 70 years
• ECOG Performance Status of 0-1
• Adequate organ and marrow function as defined below:

• Leukocytes ≥ 3,000/uL
• Absolute neutrophil count ≥ 1500/uL
• Platelets ≥ 100,000/uL
• Total bilirubin ≤ 1.5mg/dL
• AST(SGOT)/ALT(SPGT) ≤ 2 x institutional upper limit of normal
• Creatinine ≤ 1.5mg/dl and/or Creatinine Clearance ≥ 60mL/min
• Serum albumin ≥ 3.0 g/dL
• Women of child-bearing potential must agree to use adequate contraception
• Pretreatment lab values must be performed within 14 days of treatment initiation, and other baseline studies performed within 30 days prior to registration
• Subjects should have LVEF ≥ 50% by echocardiogram or MUGA scan performed within 4 weeks prior to treatment initiation
• Subjects should have breast and axillary imaging with breast MRI or breast and axillary ultrasound within 4 weeks prior to treatment initiation
• Subjects with clinically/radiologically abnormal axillary lymph nodes should have pathological confirmation of disease with image guided biopsy/fine needle aspiration.
• Subjects must be already enrolled in P.R.O.G.E.C.T observational registry
• Staging to rule out metastatic disease is recommended for subjects with clinical stage III disease
• Subjects with bilateral disease are eligible if they meet other eligibility criteria.
• Neuropathy: No baseline neuropathy grade > 2

Exclusion Criteria

• Current or anticipated use of other investigational agents
• Subject has received chemotherapy, radiotherapy or surgery for the treatment of breast cancer
• Subject with metastatic disease
• History of allergic reactions to compounds of similar chemical or biologic composition to carboplatin, docetaxel, doxorubicin, cyclophosphamide, paclitaxel, or other agents used in the study
• Subjects with inflammatory breast cancer
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
• Subject is pregnant or nursing
• Subjects with concomitant or previous malignancies within the last 5 years. Exceptions include: adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and ductal carcinoma in situ (DCIS).
• Ejection Fraction <50% on ECHO or MUGA
• Cardiac function: Subjects with congestive heart failure, myocardial infarction, unstable angina pectoris, an arterial thrombotic event, stroke or transient ischemia attack within the past 12 months, uncontrolled hypertension (Systolic BP>160 or Diastolic BP>90), uncontrolled or symptomatic arrhythmia, or grade ≥ 2 peripheral vascular disease

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Priyanka Sharma

OTHER

Sponsor Role: lead

Responsible Party

Priyanka Sharma

Medical Doctor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Priyanka Sharma, MD

Role: PRINCIPAL_INVESTIGATOR

University of Kansas Medical Center

Locations

University of Kansas Cancer Center - CRC

Fairway, Kansas, United States

Hays Medical Center

Hays, Kansas, United States

University of Kansas Cancer Center - Overland Park

Overland Park, Kansas, United States

Salina Regional Health Center

Salina, Kansas, United States

University of Kansas Cancer Center - Westwood

Westwood, Kansas, United States

Truman Medical Center

Kansas City, Missouri, United States

University of Kansas Cancer Center - South

Kansas City, Missouri, United States

University of Kansas Cancer Center - North

Kansas City, Missouri, United States

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, United States

Countries

United States

References

Sharma P, Kimler BF, O'Dea A, Nye L, Wang YY, Yoder R, Staley JM, Prochaska L, Wagner J, Amin AL, Larson K, Balanoff C, Elia M, Crane G, Madhusudhana S, Hoffmann M, Sheehan M, Rodriguez R, Finke K, Shah R, Satelli D, Shrestha A, Beck L, McKittrick R, Pluenneke R, Raja V, Beeki V, Corum L, Heldstab J, LaFaver S, Prager M, Phadnis M, Mudaranthakam DP, Jensen RA, Godwin AK, Salgado R, Mehta K, Khan Q. Randomized Phase II Trial of Anthracycline-free and Anthracycline-containing Neoadjuvant Carboplatin Chemotherapy Regimens in Stage I-III Triple-negative Breast Cancer (NeoSTOP). Clin Cancer Res. 2021 Feb 15;27(4):975-982. doi: 10.1158/1078-0432.CCR-20-3646. Epub 2020 Nov 18.

Reference Type: RESULT

PMID: 33208340 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2015-IIT-Neoadjuvant-BRST-TNBC

Identifier Type: -

Identifier Source: org_study_id