Trial Outcomes & Findings for TEEL Study- Phase 1 Tamoxifen and Ribociclib (LEE011) in Advanced ER+ (HER2 Negative) Breast Cancer (NCT NCT02586675)
NCT ID: NCT02586675
Last Updated: 2022-01-21
Results Overview
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.
COMPLETED
PHASE1
7 participants
Up to 12 months
2022-01-21
Participant Flow
Participants were enrolled at Moffitt Cancer Center March 2016 through September 2016. All participants were enrolled and treated on Cohort 1 (Ribociclib 400 mg PO D1-21; Tamoxifen 20 mg PO QD (1) only.
Participant milestones
| Measure |
Tamoxifen and Ribociclib With Goserelin
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.
|
|---|---|
|
Overall Study
STARTED
|
7
|
|
Overall Study
COMPLETED
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
TEEL Study- Phase 1 Tamoxifen and Ribociclib (LEE011) in Advanced ER+ (HER2 Negative) Breast Cancer
Baseline characteristics by cohort
| Measure |
Tamoxifen and Ribociclib With Goserelin
n=7 Participants
Phase I dose escalation followed by Phase Ib dose expansion.
|
|---|---|
|
Age, Continuous
|
54 years
STANDARD_DEVIATION 13.31 • n=93 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
7 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Up to 12 monthsPopulation: All participants
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.
Outcome measures
| Measure |
Tamoxifen and Ribociclib With Goserelin
n=7 Participants
Phase I dose escalation followed by Phase Ib dose expansion.
|
|---|---|
|
Recommended Phase II Dose (RP2D)
|
400 dose in mg
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: All participants.
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.
Outcome measures
| Measure |
Tamoxifen and Ribociclib With Goserelin
n=7 Participants
Phase I dose escalation followed by Phase Ib dose expansion.
|
|---|---|
|
Progression-free Survival (PFS) at Six Months
|
57.1 percentage of participants
Interval 17.2 to 83.7
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: All participants.
Occurrence of Overall Survival at 6 months. OS: On study date to expired date or last visit date if not deceased.
Outcome measures
| Measure |
Tamoxifen and Ribociclib With Goserelin
n=7 Participants
Phase I dose escalation followed by Phase Ib dose expansion.
|
|---|---|
|
Overall Survival (OS) at Six Months
|
83.3 percentage of participants
Interval 27.3 to 97.5
|
Adverse Events
Tamoxifen and Ribociclib With Goserelin
Serious adverse events
| Measure |
Tamoxifen and Ribociclib With Goserelin
n=7 participants at risk
All participants were enrolled and treated on Cohort 1 (Ribociclib 400 mg PO D1-21; Tamoxifen 20 mg PO QD (1) only.
|
|---|---|
|
Gastrointestinal disorders
Gastrointestinal - Other, Gastroenteritis
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
General disorders
Fatigue
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Nervous system disorders
Syncope
|
14.3%
1/7 • Number of events 3 • 1 year, 2 months
|
|
Vascular disorders
Thromboembolic event
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
Other adverse events
| Measure |
Tamoxifen and Ribociclib With Goserelin
n=7 participants at risk
All participants were enrolled and treated on Cohort 1 (Ribociclib 400 mg PO D1-21; Tamoxifen 20 mg PO QD (1) only.
|
|---|---|
|
Investigations
Neutrophil count decreased
|
57.1%
4/7 • Number of events 9 • 1 year, 2 months
|
|
Investigations
White blood cell decreased
|
57.1%
4/7 • Number of events 8 • 1 year, 2 months
|
|
Investigations
Alanine aminotransferase increased
|
42.9%
3/7 • Number of events 9 • 1 year, 2 months
|
|
Investigations
Aspartate aminotransferase increased
|
42.9%
3/7 • Number of events 9 • 1 year, 2 months
|
|
Investigations
Platelet count decreased
|
42.9%
3/7 • Number of events 3 • 1 year, 2 months
|
|
Investigations
Electrocardiogram QT corrected interval prolonged
|
28.6%
2/7 • Number of events 5 • 1 year, 2 months
|
|
Investigations
Alkaline phosphatase increased
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Investigations
Cholesterol high
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Investigations
Creatinine increased
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Investigations
Weight loss
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Metabolism and nutrition disorders
Dehydration
|
42.9%
3/7 • Number of events 4 • 1 year, 2 months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
28.6%
2/7 • Number of events 2 • 1 year, 2 months
|
|
Metabolism and nutrition disorders
Anorexia
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
14.3%
1/7 • Number of events 2 • 1 year, 2 months
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
14.3%
1/7 • Number of events 3 • 1 year, 2 months
|
|
Nervous system disorders
Dizziness
|
28.6%
2/7 • Number of events 2 • 1 year, 2 months
|
|
Nervous system disorders
Dysgeusia
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Nervous system disorders
Neuralgia
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Nervous system disorders
Syncope
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Gastrointestinal disorders
Vomiting
|
28.6%
2/7 • Number of events 2 • 1 year, 2 months
|
|
Gastrointestinal disorders
Constipation
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Gastrointestinal disorders
Diarrhea
|
14.3%
1/7 • Number of events 2 • 1 year, 2 months
|
|
Gastrointestinal disorders
Dyspepsia
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Gastrointestinal disorders
Flatulence
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Gastrointestinal disorders
Mucositis oral
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
General disorders
Pain
|
28.6%
2/7 • Number of events 2 • 1 year, 2 months
|
|
General disorders
Non-cardiac chest pain
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Infections and infestations
Otitis media
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Infections and infestations
Sinusitis
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Infections and infestations
Upper respiratory infection
|
14.3%
1/7 • Number of events 2 • 1 year, 2 months
|
|
Infections and infestations
Urinary tract infection
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
14.3%
1/7 • Number of events 2 • 1 year, 2 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Cardiac disorders
Cardiac disorders - Other, T Wave Inversion, Q Wave in II, on EKG
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Cardiac disorders
Chest pain - cardiac
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Cardiac disorders
Sinus bradycardia
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal inflammation
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Blood and lymphatic system disorders
Anemia
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Eye disorders
Eyelid function disorder
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Injury, poisoning and procedural complications
Fall
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Injury, poisoning and procedural complications
Fracture
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Renal and urinary disorders
Acute kidney injury
|
14.3%
1/7 • Number of events 1 • 1 year, 2 months
|
|
Vascular disorders
Hypotension
|
14.3%
1/7 • Number of events 4 • 1 year, 2 months
|
|
Vascular disorders
Lymphedema
|
14.3%
1/7 • Number of events 2 • 1 year, 2 months
|
Additional Information
Dr. Hatem Soliman
H. Lee Moffitt Cancer Center and Research Institute
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place