Stereotactic Radiosurgery With Abemaciclib, Ribociclib, or Palbociclib in Treating Patients With Hormone Receptor Positive Breast Cancer With Brain Metastases

NCT04585724 | Withdrawn Phase 1 DMC FDA Drug

• 4 other identifiers: STUDY00000194NCI-2019-02251RAD4615-19P30CA138292
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase I trial studies the side effects of stereotactic radiosurgery with abemaciclib, ribociclib, or palbociclib in treating patients with hormone receptor positive breast cancer that has spread to the brain (brain metasteses). Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Abemaciclib, ribociclib, and palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving abemaciclib, ribociclib, or palbociclib concurrently with stereotactic radiosurgery may reduce the side effects and/or increase the response to each of the therapies.

Conditions

Anatomic Stage IV Breast Cancer American Joint Committee on Cancer (AJCC) v8; Metastatic Breast Carcinoma; Metastatic Malignant Neoplasm in the Brain; Prognostic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Incidence of grade 3+ radiation therapy oncology central nervous system toxicity

  Rate and frequency of grade 3+ toxicity will be reported. A 95% exact confidence interval will be estimated using the Clopper-Pearson method.

  At 3 months

Secondary Outcomes (5)

• Symptomatic radiation necrosis (late toxicity)

  At 6 and 12 months

• Intracranial failure within treated lesion

  Up to 1 year

• Distant intracranial failure

  Up to 1 year

• Overall survival

  Up to 1 year

• Quality of life (QoL)

  Up to 1 year

Study Arms (3)

Treatment (abemaciclib)

EXPERIMENTAL

Beginning within 2 weeks prior to stereotactic radiosurgery, patients receive abemaciclib PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity.

Drug: Abemaciclib; Other: Quality-of-Life Assessment

Treatment (palbociclib)

EXPERIMENTAL

Beginning within 2 weeks prior to stereotactic radiosurgery, patients receive palbociclib PO QD on days 1-21. Treatment continues in the absence of disease progression or unacceptable toxicity.

Drug: Palbociclib; Other: Quality-of-Life Assessment

Treatment (ribociclib)

EXPERIMENTAL

Beginning within 2 weeks prior to stereotactic radiosurgery, patients receive ribociclib PO QD on days 1-21. Treatment continues in the absence of disease progression or unacceptable toxicity.

Other: Quality-of-Life Assessment; Drug: Ribociclib

Interventions

Abemaciclib DRUG

Given PO

Also known as: LY-2835219, LY2835219, Verzenio

Treatment (abemaciclib)

Palbociclib DRUG

Given PO

Also known as: 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one, Ibrance, PD 0332991, PD 332991, PD 991, PD-0332991

Treatment (palbociclib)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (abemaciclib); Treatment (palbociclib); Treatment (ribociclib)

Ribociclib DRUG

Given PO

Also known as: Kisqali, LEE-011, LEE011

Treatment (ribociclib)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologic diagnosis of hormone receptor positive (estrogen receptor \>= 1 percent or progesterone receptor \>= 1 percent) with HER2 negative status, past treatment, or systemic disease status with current clinical diagnosis of up to 10 brain metastases based on contrast-enhanced magnetic resonance imaging (MRI) of the brain
• Plan to start or currently receiving an Food and Drug Administration (FDA)-approved CDK4/6 inhibitor (CDKi), which must be started no later than 2 weeks prior to planned radiosurgery with plan to continue CDKi following radiosurgery
• Up to 10 brain metastases =\< 3 centimeters in greatest dimension, measured on radiation planning MRI
• Eastern Cooperative Oncology Group (ECOG)/Zubrod 0-1, or Karnofsky performance status 70-100
• Contrast-enhanced MRI brain within 4 weeks of radiosurgical intervention (radiation planning MRI)
• Patients must be able to sign informed consent prior to study entry, including assent to standard of care post-treatment surveillance contrast-enhanced magnetic resonance imaging of the brain
• Patients who are enrolled in the study, and who continue to be prescribed CDK4/6 inhibitor therapy and develop new brain metastases deemed treatable by radiosurgery, are specifically allowed to be re-treated while on study, and the new treated lesions will be separately counted by treatment category (1 to 3, 4 to 6, or 7 to 10 new treated lesions)

You may not qualify if:

• Patients with current or prior invasive malignancy unless disease free for minimum of 1 year
• Brain metastases \> 3 cm
• Brain lesions causing midline shift or herniation \> 1 cm
• Patients with unirradiated post-neurosurgical metastasectomy resection cavities, unless disease-free in the surgical bed for \>= 6 months, are prohibited from pilot study enrollment
• No patients who require resection cavity radiation for treatment of a resected brain metastasis (i.e.: standard of care treatment) are eligible for enrollment
• Receipt of chemotherapeutic agents (other than CDK4/6 inhibitors or hormone receptor-related targeted agents) within 2 weeks of planned radiosurgery date
• Prior whole brain or craniospinal radiotherapy
• Fractionated radiation to unrelated central nervous system (CNS) tumor
• Concurrent malignant CNS tumor
• Recurrent or progressive brain metastasis necessitating surgical or medical intervention (i.e.: a non-radiotherapy intervention such as steroids)
• Recurrence or progressive brain metastasis from prior surgical resection necessitating surgical or medical intervention (i.e.: a non-radiotherapy intervention)
• Brain stem metastasis \>= 1 cm
• Patients with scleroderma
• Severe acute co-morbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization in the last 3 months

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms

Interventions

abemaciclib; palbociclib; ribociclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Jim Zhong

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 7, 2020
• First Posted: October 14, 2020
• Study Start: June 12, 2020
• Primary Completion: September 13, 2021
• Study Completion: September 13, 2021
• Last Updated: October 18, 2021

Record last verified: 2021-10