Clinical trial NCT02413320: Neoadjuvant Study of Two Platinum Regimens in Triple Negative Breast Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Triple-negative Breast Cancer
Keywords: TNBC, breast cancer, neoadjuvant, carboplatin, docetaxel, paclitaxel, doxorubicin, cyclophosphamide
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
First posted: 2015-04-09
Enrollment: 101
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Pathological Complete Response
timeFrame: 20 weeks
Secondary outcomes:
measure: Number of Participants With Minimal Residual Disease
timeFrame: 20 weeks
Other outcomes:
Locations:
city: Fairway
country: United States
facility: University of Kansas Cancer Center - CRC
state: Kansas
city: Hays
country: United States
facility: Hays Medical Center
state: Kansas
city: Overland Park
country: United States
facility: University of Kansas Cancer Center - Overland Park
state: Kansas
city: Salina
country: United States
facility: Salina Regional Health Center
state: Kansas
city: Westwood
country: United States
facility: University of Kansas Cancer Center - Westwood
state: Kansas
city: Kansas City
country: United States
facility: Truman Medical Center
state: Missouri
city: Kansas City
country: United States
facility: University of Kansas Cancer Center - South
state: Missouri
city: Kansas City
country: United States
facility: University of Kansas Cancer Center - North
state: Missouri
city: Lee's Summit
country: United States
facility: University of Kansas Cancer Center - Lee's Summit
state: Missouri
Study officials:
affiliation: University of Kansas Medical Center
name: Priyanka Sharma, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.