A Single Arm Phase II Study of Palbociclib in Combination With Tamoxifen as First Line Therapy for Metastatic Hormone Receptor Positive Breast Cancer: Big Ten Cancer Research Consortium BTCRC-BRE15-016
Overview
- Phase
- Phase 2
- Intervention
- Palbociclib
- Conditions
- Hormone Receptor Positive Malignant Neoplasm of Breast
- Sponsor
- Oana Danciu, MD
- Enrollment
- 49
- Locations
- 7
- Primary Endpoint
- Progression Free Survival (PFS) Per RECIST 1.1
- Status
- Completed
- Last Updated
- 3 months ago
Overview
Brief Summary
This is a non-randomized, open-label, single-arm, multicenter, phase II study of palbociclib in combination with tamoxifen in women with HR(+)/HER2(-) advanced breast cancer who have not received prior systemic anticancer therapies for their advanced/metastatic disease.
Detailed Description
OUTLINE: This is a multi-center trial. INVESTIGATIONAL TREATMENT: * Palbociclib 125 mg will be administered orally once daily on days 1-21 (D1-D21) of each 28-day cycle. Subjects will not take palbociclib on D22-D28. * Tamoxifen 20 mg will be administered orally once daily for every day of the 28-day cycle (i.e., continuously). Palbociclib should be taken with food in combination with tamoxifen. Subjects should take their dose at approximately the same time each day. It is encouraged, but not mandatory, that premenopausal subjects will also receive treatment with goserelin or equivalent (e.g., Lupron) given as an injectable subcutaneous implant on D1 of every 28 days cycle or every 3 months. Disease assessments will be performed at the completion of every 2 cycles. Treatment will continue until disease progression, unacceptable toxicity, subject refusal, or subject death either from progression of disease, the therapy itself, or from other causes. Subjects who voluntarily stop the study, have progressive disease, or unacceptable toxicities will be followed for a total of 24 months after discontinuation of study drug. To demonstrate adequate organ function, all screening labs should be performed within 14 days prior to registration for protocol therapy: Hematological (must meet ALL of the following criteria): * Absolute neutrophil count (ANC) ≥ 1.5 × 10 9/L * Hemoglobin ≥ 9 g/dL * Platelet count ≥ 100 × 10 9/L Renal (must meet ONE of the following criteria): * Serum creatinine ≤ 1.5 × ULN * Serum creatinine \> 1.5 × ULN, estimated glomerular filtration rate (eGFR) ≥ 40 mL/min Hepatic (must meet ALL of the following criteria): * Aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases * Alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases * Total serum bilirubin ≤ 1.5 × ULN
Investigators
Oana Danciu, MD
Sponsor-Investigator
Big Ten Cancer Research Consortium
Eligibility Criteria
Inclusion Criteria
- •Subjects must meet all of the following applicable inclusion criteria to participate in this study:
- •Male or female ≥ 18 years of age at time of consent. NOTE: Both pre- and post-menopausal women are eligible. Pre-menopausal status is defined as either:
- •Last menstrual period within the last 12 months.
- •In case of therapy-induced amenorrhea, plasma estradiol and /or FSH is in the premenopausal range per local normal range.
- •Locally advanced, locoregionally recurrent, or metastatic disease, not amenable to curative therapy. NOTE: Although not required as a protocol procedure, a patient with a new metastatic lesion should be considered for biopsy whenever possible to reassess ER/PR/HER2 status if clinically indicated. If a biopsy is prospectively done as part of standard of care, the study would like to store samples for correlative research.
- •Histologically and/or cytologically confirmed diagnosis of ER positive and/or PR positive (ER \>1%, PR \>1%), HER2 negative breast cancer. NOTE: Subject has HER2-negative breast cancer (based on most recently analyzed biopsy) is defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (e.g. FISH, CISH, SISH, DISH, etc.) test is required by local laboratory testing.
- •Metastatic disease evaluable on imaging studies. Subjects may have measurable disease as per RECIST 1.1 or bone-only disease. NOTE: Bone-only subjects are eligible if their disease can be documented/ evaluated by bone scans, CT or MRI. Their disease will be assessed using MDA criteria. NOTE: Previously irradiated lesions are eligible as a target lesion only if there is documented progression of the lesion after irradiation.
- •No prior systemic anti-cancer therapy for advanced HR+ disease. NOTE: Subjects receiving adjuvant treatment with aromatase inhibitors at time of recurrence are allowed to participate. There is no AI washout period required.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- •Adequate hepatic function within 14 days prior to registration for protocol therapy defined as meeting all of the following criteria:
Exclusion Criteria
- •Subjects meeting any of the criteria below may not participate in the study:
- •Prior treatment with any CDK 4/6 inhibitor.
- •Confirmed diagnosis of HER2 positive disease.
- •Known uncontrolled or symptomatic CNS metastases. Subjects with known brain metastasis will only be eligible after their tumors have been treated with definitive resection and /or radiotherapy and they are neurologically stable for at least 1 month off steroids.
- •Advanced, symptomatic, visceral spread with a life expectancy less than 4 months.
- •Prior (neo)adjuvant treatment with tamoxifen within the 12 months before study entry.
- •Prior history of blood clots, pulmonary embolism or deep vein thrombosis.
- •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).
- •Concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated basal cell carcinoma, squamous cell skin carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
- •Any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate subject participation in the clinical study.
Arms & Interventions
Investigational Treatment
Subjects will be enrolled to determine progression-free survival (PFS) in subjects with HR(+)/HER2(-) advanced breast cancer who have not received prior systemic anti-cancer therapies. Palbociclib 125 mg will be administered orally once daily on days D1-D21 of each 28-day cycle. Subjects will not take palbociclib on D22-D28. Tamoxifen 20 mg will be administered orally once daily for every day of the 28-day cycle (i.e., continuously).
Intervention: Palbociclib
Investigational Treatment
Subjects will be enrolled to determine progression-free survival (PFS) in subjects with HR(+)/HER2(-) advanced breast cancer who have not received prior systemic anti-cancer therapies. Palbociclib 125 mg will be administered orally once daily on days D1-D21 of each 28-day cycle. Subjects will not take palbociclib on D22-D28. Tamoxifen 20 mg will be administered orally once daily for every day of the 28-day cycle (i.e., continuously).
Intervention: Tamoxifen
Outcomes
Primary Outcomes
Progression Free Survival (PFS) Per RECIST 1.1
Time Frame: Time of treatment start until the criteria for disease progression or death. Up to a maximum of 61 months.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. PFS is defined as time from registration until disease progression met by RECIST 1.1 or death from any cause.
Secondary Outcomes
- Objective Response Rates (ORR)(Up to a maximum of 61 months.)
- Overall Survival (OS)(2 years)
- Adverse Events(Adverse events (AEs) had been recorded from the time of consent until 30 days after discontinuation of study drug(s), up to a maximum of 56 months.)
- Clinical Benefit Rate (CBR)(Up to a maximum of 61 months.)