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

• Status: Terminated
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Hormones; Letrozole; R04929097

Criteria

Inclusion Criteria:

• 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)

• ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%)

• Life expectancy > 3 months

• ANC ≥ 1,000/mm³

• Platelet count ≥ 100,000/mm³

• Hemoglobin ≥ 9 g/dL

• Total bilirubin normal

• AST and ALT ≤ 2.5 times upper limit of normal

• Creatinine normal OR creatinine clearance ≥ 60 mL/min

• Baseline QTcF ≤ 470 msec

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to gamma secretase inhibitor RO4929097 or other agents used in the study

• No malabsorption syndrome or other condition that would interfere with intestinal absorption

• Able to swallow tablets

• Not serologically positive for hepatitis A, B, or C, or have a history of liver disease, other forms of hepatitis, or cirrhosis

• No uncontrolled electrolyte abnormalities including hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia despite adequate electrolyte supplementation

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• History of torsades de pointes or other significant cardiac arrhythmia other than chronic, stable atrial fibrillation

• Psychiatric illness and/or social situations that would limit compliance with study requirements

• Recovered to < grade 2 CTCAE toxicities related to prior therapy

• No prior chemotherapy, hormonal therapy, radiotherapy, or biological therapy for breast cancer

• Prior treatment for non-melanoma skin cancer or carcinoma in situ of the cervix allowed

• No prior hormone therapy for ductal carcinoma in situ (DCIS)

• No other concurrent investigational agents

• No concurrent medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®)

• No concurrent medications that are strong inducers and/or inhibitors or substrates of CYP3A4

• Switching to alternative medications allowed

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No concurrent antiarrhythmics or other medications known to prolong QTc

• No other concurrent anticancer agents or therapies

• No concurrent grapefruit juice