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

NCT02586675 | Completed Phase 1 Results

• 1 other identifier: MCC-18332
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer; Breast Cancer - Female; Breast Cancer - Male

Keywords

ER+ breast cancer; PR+ breast cancer; hormone receptor positive; HER2- breast cancer; HER2 negative; locally advanced; metastatic

Outcome Measures

Primary Outcomes (1)

• Recommended Phase II Dose (RP2D)

  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.

  Up to 12 months

Secondary Outcomes (2)

• Progression-free Survival (PFS) at Six Months

  6 months

• Overall Survival (OS) at Six Months

  6 months

Study Arms (1)

Tamoxifen and Ribociclib with Goserelin

EXPERIMENTAL

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.

Drug: Tamoxifen; Drug: Ribociclib; Drug: Goserelin

Interventions

Tamoxifen DRUG

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

Tamoxifen and Ribociclib with Goserelin

Ribociclib DRUG

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).

Also known as: LEE011, Cyclin-Dependent Kinase (CDK) Inhibitor

Tamoxifen and Ribociclib with Goserelin

Goserelin DRUG

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.

Also known as: Zoladex, Goserelin acetate

Tamoxifen and Ribociclib with Goserelin

Eligibility Criteria

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

You may qualify if:

• Histologically and/or cytologically confirmed diagnosis of Estrogen Receptor-Positive (ER+) and/or Progesterone Receptor-Positive (PR+) breast cancer by local laboratory.
• Human Epidermal growth factor Receptor 2 Negative (HER2-) breast cancer defined as a negative in situ hybridization test or an Immunohistochemistry (IHC) status of 0, 1+ or 2+. If IHC is 2+, a negative In Situ Hybridization (Fluorescence \[FISH\], Chromogenic \[CISH\], or Silver \[SISH\]) test is required by local laboratory testing.
• Participants are allowed (but not required) to have up to two lines of prior chemotherapy regimens in the metastatic setting for the dose expansion phase. For the dose escalation cohort, up to three previous lines of chemotherapy in the metastatic setting is acceptable.
• Measurable disease, i.e., at least one measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST)1.1 criteria only \*for expansion cohorts.
• For \*escalation cohorts, bone only disease is allowed. For expansion cohorts, there must be measurable disease as stated above.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1.
• Written informed consent must be obtained prior to any screening procedures and according to local guidelines.
• Adequate bone marrow and organ function.
• Must be able to swallow ribociclib and Tamoxifen capsules/tablets.
• Pre-Menopausal Women Eligibility: 1) Pre-menopausal women who received adjuvant Aromatase Inhibitor and Ovarian Suppression (AI + OS) in the adjuvant setting and completed at least 12 months of hormonal therapy. 2) Pre-menopausal women with de novo metastatic disease are eligible if they have had no prior endocrine therapy. 3) Pre-menopausal women who have not received Tamoxifen in the metastatic setting, but have received up to two lines of chemotherapy.
• Post-Menopausal Women and Men Eligibility: 1) Post-menopausal women or men who have progressed on first-line or second line therapy with an aromatase inhibitor in the metastatic setting. 2) Post-menopausal women or men who have recurred while on or after completion of adjuvant treatment with aromatase inhibitors (they have completed at least one year of AI in the adjuvant setting before progression on AI). 3) Post-menopausal women or men who are not considered candidates for treatment with an aromatase inhibitory by their oncologist, patients not willing to go on AI, or patients who were intolerant to AI.
• Post-menopausal women or men are allowed (but not required) to have up to two lines of prior chemotherapy regimens in the metastatic setting for the dose expansion phase . For the dose escalation cohort, up to three previous lines of chemotherapy in the metastatic setting is acceptable.

You may not qualify if:

• Potential participants with inflammatory breast cancer.
• Prior CDK 4/6 inhibitor exposure.
• Have received Tamoxifen in the metastatic setting (for more than 30 days) or has progressed while on Tamoxifen in the adjuvant setting.
• Known hypersensitivity to ribociclib or excipients of tamoxifen.
• A concurrent malignancy or malignancy within 3 years of starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
• Central nervous system (CNS) involvement unless specific criteria are met.
• Impairment of Gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Known history of HIV infection (testing not mandatory).
• Any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.).
• Clinically significant, uncontrolled heart disease and/or a recent events as specified in the study protocol
• Currently receiving any of the following medications and cannot be discontinued 7 days prior to starting study drug: a. Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges. b. That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5. c. That have a known risk to prolong the QT interval or induce Torsades de Pointes. d. Herbal preparations/medications, dietary supplements not prescribed by an M.D..
• Currently receiving or has received systemic corticosteroids ≤2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment.
• The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular).
• Currently receiving warfarin or other coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed.
• Participation in a prior investigational study within 30 days prior to enrollment..

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Novartis: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Breast Neoplasms; Breast Neoplasms, Male; Neoplasm Metastasis

Interventions

Tamoxifen; ribociclib; Cyclin-Dependent Kinases; Goserelin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Proline-Directed Protein Kinases; Protein Serine-Threonine Kinases; Protein Kinases; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases; Transferases; Enzymes; Enzymes and Coenzymes; Cell Cycle Proteins; Proteins; Amino Acids, Peptides, and Proteins; Intracellular Signaling Peptides and Proteins; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Oligopeptides; Nerve Tissue Proteins

Results Point of Contact

• Title: Dr. Hatem Soliman
• Organization: H. Lee Moffitt Cancer Center and Research Institute

hatem.soliman@moffitt.org

813-745-4933

Study Officials

• Roohi Ismail-Khan, MD, MSc

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: October 23, 2015
• First Posted: October 26, 2015
• Study Start: February 23, 2016
• Primary Completion: May 8, 2017
• Study Completion: October 27, 2021
• Last Updated: January 21, 2022
• Results First Posted: June 3, 2019

Record last verified: 2022-01

Locations

US (1)