The primary objective of Study I3Y-MC-JPBM is to compare treatment with LY2835219 plus NSAI therapy versus placebo plus NSAI therapy with respect to PFS in postmenopausal women with HR+, HER2- locoregionally recurrent or metastatic breast cancer who…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy measure is PFS as defined by Response Evaluation Criteria
in Solid Tumors [RECIST] v1.1.
Secondary outcome
The secondary efficacy endpoints are:
Overall Survival (OS): The time from the date of study randomization to the
date of death from any cause:
Objective Response Rate: The proportion of patients with complete response (CR)
or partial response (PR) according to RECIST v1.1;
Disease-Control Rate (DCR): The proportion of patients with CR, PR, or stable
disease (SD) according to RECIST v1.1;
Clinical Benefit Rate (CBR): The proportion of patients with CR, PR, or SD >=6
months according to RECIST v1.1;
Duration of Response (DoR): The time from the date of first evidence of a
confirmed CR or PR to the date of objective progression (according to RECIST
v1.1) or death from any cause, whichever is earlier.
Background summary
LY2835219 is an oral, selective, and potent small molecule cyclin-dependent
kinase (CDK) 4 and 6 (CDK4/6) dual inhibitor with antitumor activity within
multiple preclinical pharmacology models and an acceptable toxicity profile in
nonclinical species. LY2835219 mesylate has been shown to significantly
inhibit tumor growth in multiple murine xenograft models for human cancer.
Studies with LY2835219 across breast cancer cell lines indicate differential
sensitivity to CDK4/6 inhibition based on histological and genetic
characteristics. Growth inhibition in vitro across a diverse panel of 46
breast cancer cell lines, representing the known molecular subgroups of breast
cancer, indicates that sensitivity to CDK4/6 inhibition is greater in estrogen
receptor-positive (ER+) breast cancers with luminal histology.
Non-steroidal aromatase inhibitors (NSAI, letrozole and anastrazole) are
approved and commonly used endocrine therapy in the first-line setting for
postmenopausal women with HR+ mBC. The evaluation of LY2835219 in combination
with an NSAI is of interest since both classes of drugs have acceptable and
distinct safety profiles. The current study will assess if additional clinical
benefit may be achieved in this disease setting with this drug combination.
Study I3Y-MC-JPBM (JPBM) is a randomized, double-blind, placebo-controlled,
Phase 3 study evaluating treatment of LY2835219 with NSAI or placebo with NSAI
in postmenopausal women with HR+, human epidermal growth factor receptor
2-negative (HER2-) locoregionally recurrent or metastatic breast cancer who
have not received prior systemic therapy in this disease setting.
Study objective
The primary objective of Study I3Y-MC-JPBM is to compare treatment with
LY2835219 plus NSAI therapy versus placebo plus NSAI therapy with respect to
PFS in postmenopausal women with HR+, HER2- locoregionally recurrent or
metastatic breast cancer who have not received prior systemic therapy in this
disease setting.
The secondary objectives of the study are to compare the combination treatment
of LY2835219 and NSAI therapy versus placebo plus NSAI therapy with respect to
the following:
• overall survival [OS];
• OS rate at 1, 2, and 3 years;
• ORR (complete response [CR] + PR);
• duration of response [DoR] (CR + PR);
• DCR (CR + PR + SD);
• CBR (CR + PR + SD >= 6 months);
• safety and tolerability
• change in symptom burden using the European Organization for Research and
Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30),
EORTC QLQ-BR23 (breast) questionnaire, and health status scores from the
EuroQol 5-Dimension 5 Level (EQ-5D 5L).
• pharmacokinetics (PK) of LY2835219, its metabolites, and NSAI therapy
The exploratory objectives are:
• To explore potential biomarkers related to the mechanism of action of
LY2835219, the cell cycle, and/or the pathogenesis of breast cancer.
• To explore change in tumor size.
Study design
Study JPBM is a multicenter, randomized, double-blind, placebo-controlled Phase
3 study evaluating treatment of LY2835219 with NSAI or placebo with NSAI in
postmenopausal women with HR+, HER2- locoregionally recurrent (not amenable to
curative therapy) or metastatic breast cancer who have not received prior
systemic therapy in this disease setting. Approximately 450 patients will be
randomized 2:1 between the 2 arms. Patients will be randomized using the
following stratification factors: nature of disease (visceral metastases
versus bone-only metastases versus other) and prior (neo)adjuvant endocrine
therapy (aromatase inhibitor therapy versus other versus no prior endocrine
therapy).
Intervention
Experimental Arm A: LY2835219 orally every 12 hours on Days 1 to 28 plus
either anastrozole 1 mg or letrozole 2.5 mg once daily of a 28-day cycle
Control (Placebo) Arm B: Placebo orally every 12 hours on Days 1 to 28 plus
either anastrozole 1 mg or letrozole 2.5 mg once daily of a 28-day cycle
LY2835219 will be given as 50mg capsules.
Planned Duration of Treatment:
Treatment period: until disease progression or other discontinuation criteria
are fulfilled.
Short-term follow-up (postdiscontinuation): 30 days
Long-term follow-up (postdiscontinuation): until death
Continued Access Period: begins after study completion and ends at the end of
trial.
Study burden and risks
There are riscs associated with the use of the study drug, anastrozole,
letrozole and the study procedures.
You will find an overview in the risks appendix of the patient information
folder (appendix 3). In addition, the combination of medicines and the study
procedures can come with other, unknown risks.
Because the patients who participate in this study have a serious disease and
the treatment options are limited, it is of importance to develop medicines
that can increase life duration and quality of life as much as possible.
Although the drug is tested as a potential treatment for this form of breast
cancer, it is possible that the subject does not experience any medical
benefit. The results of the study could lead to information where patients
benefit from in the future.
Lilly Corporate Center DC 1526
Indianapolis IN 46285
IE
Lilly Corporate Center DC 1526
Indianapolis IN 46285
IE
Listed location countries
Age
Inclusion criteria
• have a diagnosis of HR+, HER2- breast cancer;
• have locoregionally recurrent disease not amenable to resection or radiation
therapy with curative intent or metastatic disease;
• have postmenopausal status due to either surgical/natural menopause or
amenorrheic (non-treatment-induced) for at least 12 months;
• have either measurable disease or nonmeasurable bone-only disease;
• have a performance status <=1 on the Eastern Cooperative Oncology Group (ECOG)
scale;
• have adequate organ function;
• have discontinued previous localized radiotherapy for palliative purposes or
for lytic lesions at risk of fracture prior to randomization and recovered from
the acute effects of therapy;
• are female and >=18 years of age;
• are able to swallow capsules;
Exclusion criteria
• have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis.
Visceral crisis is not the mere presence of visceral metastases but implies
severe organ dysfunction as assessed by symptoms and signs, laboratory studies,
and rapid progression of the disease.
• have inflammatory breast cancer.
• have clinical evidence or a history of CNS metastasis. Screening is not
required for enrollment.
• are currently receiving or have previously received endocrine therapy for
locoregionally recurrent or metastatic breast cancer. [Note: A patient may be
enrolled if she received prior (neo)adjuvant endocrine therapy (including , but
not limited to anti-estrogens or aromatase inhibitors) for localized disease.
In addition, a patient may be enrolled if she has received <=2 weeks of NSAI in
this disease setting immediately preceding screening and agrees to discontinue
NSAI until study treatment initiation.]
• have received prior (neo)adjuvant endocrine therapy (e.g., antiestrogens or
aromatase inhibitors) with a disease-free interval <=12 months from completion
of treatment.
• are currently receiving or have previously received chemotherapy for
locoregionally recurrent or metastatic breast cancer. [Note: Patients may be
enrolled if they received prior (neo)adjuvant chemotherapy for localized
disease.]
• have received prior treatment with everolimus
• have received prior treatment with any CDK4/6 inhibitor (or participated in
any CDK4/6 inhibitor clinical trial for which treatment assignment is still
blinded)
• have initiated bisphosphonates or approved RANK ligand (RANK-L) targeted
agents (for example, denosumab) <7 days prior to randomization
• are currently receiving an investigational drug in a clinical trial or
participating in any other type of medical research judged not to be
scientifically or medically compatible with this study. If a patient is
currently enrolled in a clinical trial involving non-approved use of a device,
then agreement with the investigator and Lilly clinical research physician
(CRP) is required to establish eligibility.
• have received treatment with a drug that has not received regulatory approval
for any indication within 14 or 21 days of randomization for a
nonmyelosuppressive or myelosuppressive agent, respectively.
• have had major surgery within 14 days prior to randomization to allow for
post-operative healing of the surgical wound and site(s).
• have received recent (within 28 days prior to randomization) yellow fever
vaccination.
• have serious preexisting medical conditions that, in the judgment of the
investigator, would preclude participation in this study (for example, history
of major surgical resection involving the stomach or small bowel, or
preexisting Crohn's disease or ulcerative colitis).
• have a personal history within the last 12 months of any of the following
conditions: syncope of cardiovascular etiology, ventricular tachycardia,
ventricular fibrillation, or sudden cardiac arrest.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-001502-18-NL |
| ClinicalTrials.gov | NCT02246621 |
| CCMO | NL51156.028.14 |