Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Tamoxifen

Fulvestrant

Estrogens

Palbociclib

Aromatase Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

Protein Kinase Inhibitors

Enzyme Inhibitors

Palbociclib 100mg PO daily plus Fulvestrant or Tamoxifen or another Aromatase Inhibitor at the standard doses/schedules

Palbociclib 125mg PO daily 3 out of 4 weeks plus Fulvestrant or Tamoxifen or another Aromatase Inhibitor at the standard doses/schedules

Palbociclib 100mg

Palbociclib 125mg

Fulvestrant or Tamoxifen or Aromatase Inhibitor

Anil A. Joy

The purpose of this study is to determine if the combination of endocrine therapy and Palbociclib at a daily dose of 100 mg will result in a better response to therapy with fewer dose interruptions than the proposed dosing regimen of 125 mg daily for 21 days out of a 28 day cycle in combination with endocrine therapy.

The standard or usual treatment of this type of breast cancer is endocrine therapy. Palbociclib is a new type of drug for breast cancer. Laboratory tests as well as studies in animals and people show that it may help slow the growth of breast cancer. The most widely tested regimen of Palbociclib for patients with metastatic/advanced breast cancer is 125 mg every day for 21 days out of a 28 day cycle in combination with standard endocrine (hormone) therapy. This study explores if administering a lower dose of palbociclib - 100 mg given every day of a 28 day cycle in combination with standard endocrine (hormone) therapy - may result in more tumour shrinkage and be better tolerated.

Two Different Schedules of Palbociclib + Second Line Endocrine Therapy in Estrogen Receptor Positive, HER2 Neg Advanced/Metastatic Breast Cancer

Randomized Phase II Study Comparing Two Different Schedules of Palbociclib Plus Second Line Endocrine Therapy in Women With Estrogen Receptor Positive, HER2 Negative Advanced/Metastatic Breast Cancer

progression free survival (PFS) is defined as time from randomization to progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Response rate = Number of (Complete response + partial response) / total treated patients. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

For patients with complete or partial response, duration of response is defined as days from first recorded response to the first date of recurrent or progression or death.

Time from randomization to death of any cause.

Pfizer

Canadian Cancer Trials Group

Palbociclib 100mg PO daily plus Fulvestrant or Tamoxifen or another Aromatase Inhibitor at the standard doses/schedules

Palbociclib 100mg: 100mg PO daily

Fulvestrant or Tamoxifen or Aromatase Inhibitor: given at the standard doses/schedules

Palbociclib (100mg)

Palbociclib 125mg PO daily 3 out of 4 weeks plus Fulvestrant or Tamoxifen or another Aromatase Inhibitor at the standard doses/schedules

Palbociclib 125mg: 125mg PO daily 3 weeks out of 4

Fulvestrant or Tamoxifen or Aromatase Inhibitor: given at the standard doses/schedules

Palbociclib (125mg)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Canada

Region of Enrollment

Menopausal Status

Baseline variables were reported using intend to treat principle

Dr. Wendy Parulekar

Progression Free Survival Using the RECIST 1.1 Criteria

Only patients received protocol treatment were included in this analysis

Number of Participants With Response or No Response

Duration of Response

Overall Survival

Overall Study

Rare Diseases

Myotonic Dystrophy Type 1

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Trastuzumab

Letrozole

Mitogens

Ado-Trastuzumab Emtansine

Adenosine

Antineoplastic Agents, Immunological

Tubulin Modulators

Antimitotic Agents

Immunotoxins

Immunoconjugates

Immunologic Factors

Palbociclib 75 milligrams (mg) by mouth (PO) daily Letrozole 2.5 mg PO Daily Ado-trastuzumab Emtansine (T-DM1) 3.6 milligrams per kilograms (mg/kg) intravenous (IV) Day 1

Palbociclib 100 milligrams (mg) by mouth (PO) daily Letrozole 2.5 mg PO Daily Ado-trastuzumab Emtansine (T-DM1) 3.6 milligrams per kilograms (mg/kg) intravenous (IV) Day 1

Palbociclib 125 milligrams (mg) by mouth (PO) daily Letrozole 2.5 mg PO Daily Ado-trastuzumab Emtansine (T-DM1) 3.6 milligrams per kilograms (mg/kg) intravenous (IV) Day 1

Recommended Phase 2 dose (RP2D; determined during Phase 1 Safety Run In) Palbociclib by mouth (PO) daily Letrozole 2.5 mg PO Daily Ado-trastuzumab Emtansine (T-DM1) 3.6 milligrams per kilograms (mg/kg) intravenous (IV) Day 1

Palbociclib 75mg

Letrozole 2.5mg

T-DM1

Lauren Nye, MD

This study will determine the recommend dose of palbociclib in combination with letrozole and another medication, Ado-trastuzumab emtansine (T-DM1). Additionally, researchers will determine how well this recommended dose will improve outcomes in this type of advanced breast cancer.

The study will include a safety lead-in with escalating dosing of palbociclib to determine the recommended phase II dose (RP2D) of palbociclib in this combination and an expanded phase II of palbociclib at the RP2D in combination with letrozole and Ado- trastuzumab Emtansine (T-DM1).

The starting dose of palbociclib will be 75 milligrams (mg) by mouth (PO) daily for each 21 day cycle. If 0 of 3 patients at the 75mg dose level experience a dose limiting toxicity (DLT), the next 3 patients will be enrolled at the next higher dosing cohort of 100mg PO daily for each 21 day cycle. If 0 of 3 patients at the 100mg dose level experience a DLT, the next 3 patients will be enrolled at the next higher dosing cohort of 125mg PO daily for each 21 day cycle. If 0 of 3 patients at the 125mg dose level experience a DLT, 125mg PO daily of palbociclib will be the phase II recommended dose used in the phase II expanded cohort. Patients receiving the phase II recommended dose in phase I will be enrolled in phase II of the study.

During safety lead-in and expanded phase II, Letrozole 2.5mg PO will be administered daily for each 21 day cycle and T-DM1 3.6 milligrams per kilograms intravenously (IV) will be administered on Day 1 of each 21 day cycle.

Palbociclib in Estrogen Receptor Positive (ER+) Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Metastatic Breast Cancer

A Phase I/II Study of Palbociclib, Letrozole and T-DM1 in Trastuzumab Refractory Estrogen Receptor Positive (ER+) and HER2 Positive Metastatic Breast Cancer

Determine overall response rate (ORR), defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Defined per Common Terminology Criteria for Adverse Events (CTCAE) v4.03

Determine safety and tolerability of the intervention, defined per Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

PRO-AE score defined per Patient Reported Outcome Measurement Information System (PROMIS) and Breast Cancer Prevention Trial (BCPT) Symptom Checklist.

Defined per maximum observed concentration (Cmax) and time of Cmax (Tmax).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Two Different Schedules of Palbociclib + Second Line Endocrine Therapy in Estrogen Receptor Positive, HER2 Neg Advanced/Metastatic Breast Cancer	NCT02630693	Breast Cancer	Palbociclib 100... Palbociclib 125... Fulvestrant or ...	18 Years -	Canadian Cancer Trials Group
Palbociclib in Estrogen Receptor Positive (ER+) Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Metastatic Breast Cancer	NCT03709082	HER2-positive B... Breast Cancer M...	Palbociclib 75m... Letrozole 2.5mg T-DM1 Palbociclib 100... Palbociclib 125... Palbociclib	18 Years -	University of Kansas Medical Center

Spots Global Cancer Trial Database for palbociclib 100mg