RO4929097 and Letrozole in Treating Post-Menopausal Women With Hormone Receptor-Positive Stage II or Stage III Breast Cancer

NCT01208441 | Terminated Phase 1

• 6 other identifiers: NCI-2011-02487UPCI-09-080CDR0000683397UPCI 09-0808554U01CA099168
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial is studying the side effects and best dose of RO4929097 when given together with letrozole in treating post-menopausal women with stage II or stage III breast cancer. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving RO4929097 together with letrozole may be an effective treatment for breast cancer.

Conditions

Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer

Outcome Measures

Primary Outcomes (1)

• MTD defined as the dose level at which no more than 1 of 6 patients experience a DLT, and the dose below that at which at least 2/6 patients have DLT according to NCI CTCAE version 4.0

  21 days

Secondary Outcomes (20)

• Measurement of NOTCH 1 and 4, activated NOTCH (ICN), Hey 1 and NOTCH ligands (DLL4 and Jagged 1)

  Baseline

• Measurement of NOTCH 1 and 4, activated NOTCH (ICN), Hey 1 and NOTCH ligands (DLL4 and Jagged 1)

  21 days

• Measurement of NOTCH 1 and 4, activated NOTCH (ICN), Hey 1 and NOTCH ligands (DLL4 and Jagged 1)

  42 days

• Measurement of NOTCH 1 and 4, activated NOTCH (ICN), Hey 1 and NOTCH ligands (DLL4 and Jagged 1)

  At time of surgery

• Genomic analysis of RNA transcriptome, mirco-RNA transcriptome, and DNA methylation

  Baseline

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive oral letrozole once daily on days 1-21. Beginning in course 2, patients also receive oral RO4929097 on days 1-3, 8-10, and 15-18. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 1 week after completion of neoadjuvant therapy, patients undergo surgery or tumor biopsy. Patients continue to receive oral letrozole once daily during surgery and for an additional 4 weeks.

Drug: letrozole; Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097; Procedure: therapeutic conventional surgery; Procedure: breast biopsy; Other: diagnostic laboratory biomarker analysis; Other: pharmacological study

Interventions

letrozole DRUG

Also known as: CGS 20267, Femara, LTZ

Arm I

gamma-secretase/Notch signalling pathway inhibitor RO4929097 DRUG

Also known as: R4733, RO4929097

Arm I

therapeutic conventional surgery PROCEDURE

Arm I

breast biopsy PROCEDURE

Also known as: biopsy of breast

Arm I

diagnostic laboratory biomarker analysis OTHER

Arm I

pharmacological study OTHER

Also known as: pharmacological studies

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed invasive breast cancer
• Stage II or III disease (T2-T3, N0-2)
• No N3, T4 disease
• Estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+)
• H score ≥ 10 or positivity ≥ 10%
• HER2 negative as determined by IHC (1 or 2+) or FISH (\< 2.0+)
• Bilateral disease allowed as long as all tumors are ER+ and ≥ 1 is T2-T3
• Patient must have disease that is palpable on physical exam and able to be imaged via breast ultrasound
• Defined as ≥ 1 T2 tumor \> 2 cm
• Multifocal disease allowed provided that ≥ 1 of the tumors is \> 2 cm
• No metastatic disease by CT scans of the chest, abdomen, and pelvis, a PET/CT bone scan, or nuclear medicine bone scan
• No inflammatory breast cancer or presence of breast tumor cells in the dermal lymphatics of the breast
• Post-menopausal meeting 1 of the following criteria:
• Bilateral oophorectomy
• Age ≥ 50 years and amenorrheic for \> 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression (spontaneous amenorrhea)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole; 2,2-dimethyl-N-(6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-N'-(2,2,3,3,3-pentafluoropropyl)malonamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Shannon Puhalla

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2010
• First Posted: September 24, 2010
• Study Start: November 1, 2010
• Primary Completion: December 1, 2011
• Last Updated: September 30, 2013

Record last verified: 2013-09

Locations

US (3)