Clinical trial NCT02520063: Combination of Letrozole, Everolimus and TRC105 in Postmenopausal Women With Hormone-Receptor Positive and Her2 Negative Breast Cancer
Official title: A Phase I/II Study of Preoperative (Neoadjuvant) Combination of Letrozole (Femara), Everolimus (Afinitor), and TRC105 in Postmenopausal Women With Newly Diagnosed Local or Locally Advanced Potentially Resectable Hormone-Receptor Positive and Her2 Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: hormone-receptor positive breast cancer
Her2 negative breast cancer
neoadjuvant
everolimus
TRC105
letrozole
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
name: Tracon Pharmaceuticals Inc.
First posted: 2015-08-11
Enrollment: 15
Sex: FEMALE
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will test how well a new combination of three drugs (Letrozole, Everolimus, and TRC105) is tolerated and how well it works in Stage 2 and 3 breast cancer when given prior to definitive surgery. Letrozole blocks the estrogen receptor expressed by many breast cancers while everolimus blocks signals that drive cancer cells to grow. TRC105 is an investigational drug that blocks the formation and growth of blood vessels that feed the cancer and promote its growth. The goal of this study is to investigate the safety and efficacy of this multitargeted approach in breast cancer.

Detailed description: In postmenopausal women with hormone receptor-positive and Her2 negative non-metastatic breast cancer, downstaging or the achievement of a complete pathologic remission before definitive surgery has been associated with the lowest risk of recurrence of breast cancer. In order to achieve a better response in these patients in the preoperative setting, this study combines 3 potentially synergistic agents. Letrozole blocks the synthesis of estrogens and, in doing so, deprives the tumor from hormones which drive its growth. Everolimus is a drug that blocks growth factor signaling which is essential for tumor cells to maintain their growth and proliferation. Everolimus has already been shown to work very well in this subtype of breast cancer in the recurrent and metastatic setting. TRC105 is an investigational agent that prevents the formation and growth of new blood vessels that support tumors by providing oxygen and nutrients.

The study has 2 components. First the investigators will determine the ideal in terms of tolerance combination of doses of the 3 agents. Once the ideal regimen is determined, more patients will be treated with the investigational combination. During this second stage, the investigators will get a preliminary idea of how effective the investigational therapy is. Further studies will need to be done to confirm the efficacy of the investigational combination.

Eligibility criteria: Inclusion Criteria:

* Recent diagnosis of hormone receptor positive and HER2 negative breast cancer.
* Stage 2 and 3 hormone receptor positive and HER2 negative breast cancer (stage T2-4 but not inflammatory, N0-2, M0).
* Histological grade I, II or III according to the modified Bloom Richardson scale.
* No prior treatment specific for breast cancer.
* Postmenopausal status as defined by the National Comprehensive Cancer Network.
* ECOG performance status \< 2 (Karnofsky \> 60%).
* Must have signed study-specific informed consent.
* Liver Function Tests \< 2.5 times the upper normal limit (UNL).
* ANC ≥ 1,500/mm3, platelets ≥ 100,000/mm3, Hemoglobin ≥ 10g%.
* Renal function: serum creatinine \< 1.5 institutional UNL or creatinine clearance \> 40 cc/min.

Exclusion Criteria:

* Inflammatory breast cancer.
* Pre- and peri-menopausal state.
* Pregnancy.
* Metastatic disease.
* HER2 positive breast cancer by immunohistochemistry or FISH.
* Triple negative breast cancer (hormone receptor and Her2 negative).
* Disease that cannot be followed by imaging studies.

Primary outcomes:
measure: Number of Participants Who Experienced Dose-limiting Toxicities
timeFrame: 4 weeks
Secondary outcomes:
measure: Rates of Pathologic Complete Remission (pCR)
timeFrame: 24 weeks up to time of surgery
measure: C Max - Letrozole
timeFrame: Day 1 and Day 29
measure: Tumor Proliferation Changes
timeFrame: 24 weeks (pretreatment to time of definitive surgery)
measure: T Max - Letrozole
timeFrame: Day 1
measure: AUC - Letrozole
timeFrame: Day 1 and Day 29
measure: T 1/2 - Letrozole
timeFrame: Day 1
measure: C Max - Everolimus
timeFrame: Day 1 and Day 29
measure: T Max Everolimus
timeFrame: Day 1
measure: AUC - Everolimus
timeFrame: Day 1 and Day 29
measure: T 1/2 - Everolimus
timeFrame: day 1
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Erica Stringer-Reasor, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Erica Stringer-Reasor, MD
role: PRINCIPAL_INVESTIGATOR
References: