Neoadjuvant Study of Two Platinum Regimens in Triple Negative Breast Cancer (NeoSTOP)

• ClinicalTrials.gov Identifier: NCT02413320
• Recruitment Status: Completed
• First Posted: April 9, 2015
• Results First Posted: April 30, 2021
• Last Update Posted: May 10, 2021
• Sponsor: Priyanka Sharma
• Information provided by (Responsible Party): Priyanka Sharma, University of Kansas Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Triple-negative Breast Cancer	Drug: Paclitaxel; Drug: Carboplatin; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 101 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Open Label Phase II Trial of Neoadjuvant Carboplatin Plus Docetaxel or Carboplatin Plus Paclitaxel Followed by Doxorubicin Plus Cyclophosphamide in Stage I-III Triple-negative Breast Cancer
• Study Start Date: July 2015
• Actual Primary Completion Date: February 1, 2019
• Actual Study Completion Date: February 1, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 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	Drug: Paclitaxel; Other Name: taxol; Drug: Carboplatin; Other Name: paraplatin; Drug: Doxorubicin; Other Name: adriamycin; Drug: Cyclophosphamide; Other Name: cytoxin, procytox
Active Comparator: Carboplatin + Docetaxel; Carboplatin (AUC 6) given IV and Docetaxel (75mg/m2) given IV every 21 days x 6 cycles	Drug: Carboplatin; Other Name: paraplatin; Drug: Docetaxel; Other Name: taxotere

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Pathological Complete Response [ Time Frame: 20 weeks ]
   To evaluate the pathological complete response rates with neoadjuvant chemotherapy regimens of carboplatin plus paclitaxel x 4 cycles followed by doxorubicin plus cyclophosphamide X 4 cycles and carboplatin plus docetaxel X 6 cycles in subjects with stage I-III triple-negative breast cancer. Pathological complete response is defined as no evidence of disease in the breast and axilla at the time of pathology review except for DCIS.

Secondary Outcome Measures :

1. Number of Participants With Minimal Residual Disease [ Time Frame: 20 weeks ]
   To evaluate minimal residual disease rates (residual cancer burden 0+1) with two neoadjuvant chemotherapy regimens in subjects with stage I-III triple-negative breast cancer.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Kansas

University of Kansas Cancer Center - CRC

Fairway, Kansas, United States, 66205

Hays Medical Center

Hays, Kansas, United States, 67601

University of Kansas Cancer Center - Overland Park

Overland Park, Kansas, United States, 66210

Salina Regional Health Center

Salina, Kansas, United States, 67401

University of Kansas Cancer Center - Westwood

Westwood, Kansas, United States, 66205

United States, Missouri

Truman Medical Center

Kansas City, Missouri, United States, 64108

University of Kansas Cancer Center - South

Kansas City, Missouri, United States, 64131

University of Kansas Cancer Center - North

Kansas City, Missouri, United States, 64154

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, United States, 64064

Sponsors and Collaborators

Priyanka Sharma

Investigators

• Principal Investigator: Priyanka Sharma, MD; University of Kansas Medical Center

  Study Documents (Full-Text)

Documents provided by Priyanka Sharma, University of Kansas Medical Center:

Study Protocol and Statistical Analysis Plan  [PDF] May 17, 2016

More Information

Publications of Results:

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.

• Responsible Party: Priyanka Sharma, Medical Doctor, University of Kansas Medical Center
• ClinicalTrials.gov Identifier: NCT02413320
• Other Study ID Numbers: 2015-IIT-Neoadjuvant-BRST-TNBC
• First Posted: April 9, 2015
• Results First Posted: April 30, 2021
• Last Update Posted: May 10, 2021
• Last Verified: May 2021

Keywords provided by Priyanka Sharma, University of Kansas Medical Center:

TNBC, breast cancer, neoadjuvant, carboplatin, docetaxel, paclitaxel, doxorubicin, cyclophosphamide

Additional relevant MeSH terms:

Breast Neoplasms; Triple Negative Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Paclitaxel; Docetaxel; Cyclophosphamide; Carboplatin; Doxorubicin; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors