Neoplasms

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Breast Neoplasms

Breast Diseases

Skin Diseases

Bone Density Conservation Agents

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Tamoxifen

Hormones

Goserelin

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Antineoplastic Agents, Hormonal

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

Phase I dose escalation followed by Phase Ib dose expansion. Tamoxifen and Ribociclib, with Goserelin added for premenopausal or peri-menopausal participants. Ribociclib: Capsules/Tablets for oral use 400 mg OR 600 mg Days 1-21 of each 28 day cycle or daily. Tamoxifen: Tablets for oral use 20 mg daily (all days of every cycle without interruption). Goserelin: Subcutaneous injection 3.6 mg Day 1 of each 28 day cycle.

Tamoxifen will be taken orally once daily on a continuous daily schedule (e.g., days 1-28 of each 28 day cycle).

Ribociclib (LEE011) will be taken orally once daily on days 1-21 of each 28 day cycle. Days 22-28 will be a "rest" period from dosing with Ribociclib. In the continuous cohort, 400 mg ribociclib will be given daily (QD).

Ribociclib

Goserelin will be given as an injectable subcutaneous implant on day 1 of every 28 day cycle. This will be given in pre-menopausal and peri-menopausal women.

Roohi Ismail-Khan, MD, MSc

The purpose of this study is to find out if the investigational drug Ribociclib (LEE011), when taken with standard treatment (Tamoxifen +/- Goserelin) is safe and has beneficial effects in pre-menopausal and post-menopausal women and men who have a type of breast cancer known as hormone receptor positive/HER2- breast cancer.

Phase I Dose Escalation:

The phase I portion of the study is a dose escalation to confirm the safety of the combination and to determine the Maximum Tolerated Dose (MTD) and the Recommended Phase II Dose (RP2D) for ribociclib with Tamoxifen.

Phase I will be conducted in all participants with Hormone Receptor Positive (HR+)/Human Epidermal growth factor Receptor 2 Negative (HER2-) locally advanced or metastatic breast cancer with any prior endocrine therapy and up to three prior cytotoxic chemotherapy regimens administered in the metastatic or locally advanced setting.

Phase Ib Dose Expansion:

Phase I trials are increasingly including dose-expansion cohorts (Ib) after the maximum-tolerated dose has been reached to better characterize the toxicity profile and identify early signs of efficacy within this specific disease population. The investigators' goal is to assess the anti-tumor activity Ribociclib + Tamoxifen and to further evaluate their safety in adult patients with HR+/HER2- locally advanced or metastatic breast cancer. Patients in the phase 1b expansion will have the same exclusion and inclusion criteria except that they will only be allowed to have up to two lines of cytotoxic chemotherapy in the metastatic setting.

TEEL Study- Phase 1 Tamoxifen and Ribociclib (LEE011) in Advanced ER+ (HER2 Negative) Breast Cancer

The TEEL Study: A Phase I Trial of Tamoxifen With Ribociclib (LEE011) in Adult Patients With Advanced ER+ (HER2 Negative) Breast Cancer

400-600 mg of Ribociclib, when taken with Tamoxifen 20 mg. The Phase I portion of the study is a dose escalation to confirm the dose limiting toxicity (DLT) and the RP2D for ribociclib with Tamoxifen. DLT is defined as an adverse event or abnormal laboratory value assessed as having a reasonable possibility related to the study medication, unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 28 days of treatment (cycle 1) with LEE011 and Tamoxifen. National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 4.03 will be used for all grading. In this study, a DLT will occur if CTCAE grade 4 neutropenia lasts more than 4 consecutive days, if CTCAE grade 3 thrombocytopenia is associated with clinically significant bleeding or if there is grade 4 thrombocytopenia.

Occurrence of Progression Survival at 6 months. PFS: On study date to date of progression or the same as overall survival time if not progressed. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Occurrence of Overall Survival at 6 months. OS: On study date to expired date or last visit date if not deceased.

Novartis

H. Lee Moffitt Cancer Center and Research Institute

All participants were enrolled and treated on Cohort 1 (Ribociclib 400 mg PO D1-21; Tamoxifen 20 mg PO QD (1) only.

Tamoxifen and Ribociclib With Goserelin

Phase I dose escalation followed by Phase Ib dose expansion.

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Hatem Soliman

Recommended Phase II Dose (RP2D)

Progression-free Survival (PFS) at Six Months

Overall Survival (OS) at Six Months

Phase I dose escalation followed by Phase Ib dose expansion. Tamoxifen and Ribociclib, with Goserelin added for premenopausal or peri-menopausal participants. Ribociclib: Capsules/Tablets for oral use 400 mg OR 600 mg Days 1-21 of each 28 day cycle or daily. Tamoxifen: Tablets for oral use 20 mg daily (all days of every cycle without interruption). Goserelin: Subcutaneous injection 3.6 mg Day 1 of each 28 day cycle.

Tamoxifen: Tamoxifen will be taken orally once daily on a continuous daily schedule (e.g., days 1-28 of each 28 day cycle).

Ribociclib: Ribociclib (LEE011) will be taken orally once daily on days 1-21 of each 28 day cycle. Days 22-28 will be a "rest" period from dosing with Ribociclib. In the continuous cohort, 400 mg ribociclib will be given daily (QD).

Goserelin: Goserelin will be given as an injectable subcutaneous implant on day 1 of every 28 day cycle. This will be given in pre-menopausal and peri-menopausal women.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
TEEL Study- Phase 1 Tamoxifen and Ribociclib (LEE011) in Advanced ER+ (HER2 Negative) Breast Cancer	NCT02586675	Breast Cancer Breast Cancer -... Breast Cancer -...	Tamoxifen Ribociclib Goserelin	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
TEEL Study- Phase 1 Tamoxifen and Ribociclib (LEE011) in Advanced ER+ (HER2 Negative) Breast Cancer	NCT02586675	Breast Cancer Breast Cancer -... Breast Cancer -...	Tamoxifen Ribociclib Goserelin	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
TEEL Study- Phase 1 Tamoxifen and Ribociclib (LEE011) in Advanced ER+ (HER2 Negative) Breast Cancer	NCT02586675	Breast Cancer Breast Cancer -... Breast Cancer -...	Tamoxifen Ribociclib Goserelin	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for pr+ breast cancer