Clinical Trials /

Preoperative Combination of Letrozole, Everolimus, and TRC105 in Postmenopausal Hormone-Receptor Positive and Her2 Negative Breast Cancer

NCT02520063

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT02520063

Trial Eligibility

Document

Title

  • Brief Title: Preoperative Combination of Letrozole, Everolimus, and TRC105 in Postmenopausal 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

Clinical Trial IDs

  • ORG STUDY ID: F150701004 (UAB 1514)
  • NCT ID: NCT02520063

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
LetrozoleFemaraPhase I Cohort -1
EverolimusAfinitorPhase I Cohort -1
TRC105Phase I Cohort -1

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Phase I Cohort 1ExperimentalLetrozole 2.5 mg PO daily until surgery, everolimus 5 mg PO daily for 24 weeks, and TRC105 15 mg/kg IV q 2 weeks for 24 weeks
  • Letrozole
  • Everolimus
  • TRC105
Phase I Cohort 2ExperimentalLetrozole 2.5 mg PO daily until surgery, everolimus 10 mg PO daily for 24 weeks, and TRC105 15 mg/kg IV q 2 weeks for 24 weeks
  • Letrozole
  • Everolimus
  • TRC105
Phase I Cohort -1ExperimentalLetrozole 2.5 mg PO daily until surgery, everolimus 5 mg PO daily for 24 weeks, and TRC105 10 mg/kg IV q 2 weeks for 24 weeks
  • Letrozole
  • Everolimus
  • TRC105
Phase IIExperimentalLetrozole 2.5 mg PO daily until surgery, everolimus 5 or 10 mg PO daily for 24 weeks, and TRC105 15 or 10 mg/kg IV q 2 weeks for 24 weeks. Dose and regimen to be determined based on data from the phase I component.
  • Letrozole
  • Everolimus
  • TRC105

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.
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD)
Time Frame:4 weeks
Safety Issue:
Description:The highest dose at which 0 out of the first 3 or 1 out of a total of 6 patients experience dose limiting toxicity associated with the combination of letrozole with everolimus and TRC105 during the first cycle of therapy.

Secondary Outcome Measures

Measure:Rates of pathologic complete remission (pCR)
Time Frame:24 weeks up to time of surgery
Safety Issue:
Description:The 2-dimensional size of the surgically excised residual tumor will be measure and compared to the radiographic size of the tumor at baseline.
Measure:C max
Time Frame:collections over 24 hours on Day 1 and Day 25
Safety Issue:
Description:Maximum serum concentration of the interaction between TRC105 and everolimus
Measure:Tumor proliferation changes
Time Frame:24 weeks up to time of surgery
Safety Issue:
Description:Determine the changes in tumor cell proliferation by means of changes in Ki67 expression and changes in serum concentration of markers of angiogenesis
Measure:T max
Time Frame:collections over 24 hours on Day 1 and Day 25
Safety Issue:
Description:Time of maximum serum concentration of the interaction between TRC105 and everolimus
Measure:AUC
Time Frame:collections over 24 hours on Day 1 and Day 25
Safety Issue:
Description:Area under the serum concentration versus time curve
Measure:T 1/2
Time Frame:collections over 24 hours on Day 1 and Day 25
Safety Issue:
Description:Terminal half-life of the interaction between TRC105 and everolimus

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:University of Alabama at Birmingham

Trial Keywords

  • hormone-receptor positive breast cancer
  • Her2 negative breast cancer
  • neoadjuvant
  • everolimus
  • TRC105
  • letrozole

Last Updated

June 14, 2021