Clinical Trials /

Radiation Therapy Followed by Intrathecal Trastuzumab/Pertuzumab in HER2+ Breast Leptomeningeal Disease

NCT04588545

Description:

The purpose of this study is to find out if radiation therapy followed by intrathecal trastuzumab and pertuzumab is safe and will result in improved survival in HER2 positive breast cancer which has metastasized to the leptomeninges.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Radiation Therapy Followed by Intrathecal Trastuzumab/Pertuzumab in HER2+ Breast Leptomeningeal Disease
  • Official Title: Phase I/II Study of Radiation Therapy Followed by Intrathecal Trastuzumab/Pertuzumab in the Management of HER2+ Breast Leptomeningeal Disease

Clinical Trial IDs

  • ORG STUDY ID: MCC-20487
  • SECONDARY ID: ML41590
  • NCT ID: NCT04588545

Conditions

  • HER2-positive Breast Cancer
  • Leptomeningeal Metastasis
  • Leptomeningeal Disease

Interventions

DrugSynonymsArms
PertuzumabRadiation Therapy followed by 10 mg Pertuzumab and 80 mg Trastuzumab
TrastuzumabRadiation Therapy followed by 10 mg Pertuzumab and 80 mg Trastuzumab

Purpose

The purpose of this study is to find out if radiation therapy followed by intrathecal trastuzumab and pertuzumab is safe and will result in improved survival in HER2 positive breast cancer which has metastasized to the leptomeninges.

Detailed Description

      The study is designed as a prospective, single-arm, nonrandomized, open-label, phase I/II
      trial of radiation therapy (RT) followed by intrathecal (IT) trastuzumab/pertuzumab in the
      management of HER2+ breast leptomeningeal disease (LMD). Treatment will be initiated with RT,
      whole brain RT (WBRT) and/or focal brain/spine RT followed by IT trastuzumab/pertuzumab.
    

Trial Arms

NameTypeDescriptionInterventions
Radiation Therapy followed by 10 mg Pertuzumab and 80 mg TrastuzumabExperimentalTreatment will be initiated with radiation therapy (RT), either whole brain radiation therapy or focal brain/spine radiation therapy. Participants will be treated at dose level 1 of 4 with 10 mg pertuzumab along with 80 mg trastuzumab via Ommaya reservoir over 2-5 minutes. Pertuzumab and trastuzumab will be administered sequentially. Participants will be observed 30 to 60 minutes before commencing the next agent. Participants will be treated twice a week for 4 weeks, once a week for 4 weeks, and then once every 2 weeks.
  • Pertuzumab
  • Trastuzumab
Radiation Therapy followed by 20 mg Pertuzumab and 80 mg TrastuzumabExperimentalTreatment will be initiated with radiation therapy (RT), either whole brain radiation therapy or focal brain/spine radiation therapy. Participants will be treated at dose level 2 of 4 with 20 mg pertuzumab along with 80 mg trastuzumab via Ommaya reservoir over 2-5 minutes. Pertuzumab and trastuzumab will be administered sequentially. Participants will be observed 30 to 60 minutes before commencing the next agent. Participants will be treated twice a week for 4 weeks, once a week for 4 weeks, and then once every 2 weeks.
  • Pertuzumab
  • Trastuzumab
Radiation Therapy followed by 40 mg Pertuzumab and 80 mg TrastuzumabExperimentalTreatment will be initiated with radiation therapy (RT), either whole brain radiation therapy or focal brain/spine radiation therapy. Participants will be treated at dose level 3 of 4 with 40 mg pertuzumab along with 80 mg trastuzumab via Ommaya reservoir over 2-5 minutes. Pertuzumab and trastuzumab will be administered sequentially. Participants will be observed 30 to 60 minutes before commencing the next agent. Participants will be treated twice a week for 4 weeks, once a week for 4 weeks, and then once every 2 weeks.
  • Pertuzumab
  • Trastuzumab
Radiation Therapy followed by 80 mg Pertuzumab and 80 mg TrastuzumabExperimentalTreatment will be initiated with radiation therapy (RT), either whole brain radiation therapy or focal brain/spine radiation therapy. Participants will be treated at dose level 4 of 4 with 80 mg pertuzumab along with 80 mg trastuzumab via Ommaya reservoir over 2-5 minutes. Pertuzumab and trastuzumab will be administered sequentially. Participants will be observed 30 to 60 minutes before commencing the next agent. Participants will be treated twice a week for 4 weeks, once a week for 4 weeks, and then once every 2 weeks.
  • Pertuzumab
  • Trastuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmation of HER2 positivity. All patients with HER2+ cancers will be allowed to
             enroll if they have leptomeningeal disease (LMD). Patients may be IHC 3+ and/or
             FISH-positive. IHC 2+ HER2 patients are eligible with reflex FISH-positive testing
             with the ratio ≥2.0

          -  Participants may have concomitant brain metastases

          -  Cerebrospinal fluid (CSF) sampling is required to document LMD if not documented by
             MRI. Participants are still eligible CSF is negative but LMD disease is documented on
             MRI

          -  Life expectancy greater than 8 weeks

          -  Consent to pretreatment tumor biopsy or retrieval of archival tissue

          -  Normal renal (creatinine <1.5 × upper limit of normal [ULN]), liver (bilirubin < 1.5 ×
             ULN, transaminases <3.0 × ULN, except in known hepatic disease, wherein may be <5 ×
             ULN) and blood counts (white blood cells ≥2.5, neutrophils ≥1000, platelets ≥75,000,
             hemoglobin ≥8)

          -  LVEF >50%

          -  KPS >/= 60

          -  Patients with surgery within 14 days should have recovered from all effects of the
             surgery and be cleared by their surgeon

          -  There is no limit on prior systemic or IT therapies

          -  Must be willing to have an Ommaya reservoir placed and a candidate for an Ommaya
             reservoir placement

          -  Women of childbearing potential and sexually active males must commit to the use of
             effective contraception while on study. Contraception methods should start a minimum
             of 14 days before the first administration of study drug and continue for the duration
             of study treatment and for at least 7 months after the last dose of study treatment.

          -  Ability to sign informed consent.

          -  Patients may continue treatment with IV trastuzumab, pertuzumab, or other
             HER2-directed, hormonal, or chemotherapeutic agents if controlling systemic disease
             and leptomeningeal metastases that developed while on these therapies. In addition, at
             time of systemic progression, patients may start additional agents at the discretion
             of the treating physician according to criteria per protocol.

        Exclusion Criteria:

          -  Current or prior participation in a study of an investigational agent or
             investigational device within 2 weeks of the first dose of study treatment

          -  Cannot be on systemic agents (chemotherapy) that have Central Nervous System (CNS)
             penetration (temozolomide, carmustine, lomustine, etoposide, capecitabine,
             carboplatin, vinorelbine, bevacizumab, irinotecan, and topotecan) unless they develop
             or have progressive or persistent leptomeningeal metastases while on these agent(s).
             See protocol for additional information regarding systemic therapies.

          -  Major surgery or significant traumatic injury that has not been recovered from 14 days
             before the initiation of study drug

          -  Symptomatic lung disease resulting in shortness of breath at rest

          -  Women who are pregnant or breastfeeding

          -  History of allergy or hypersensitivity to any of the study drugs or study drug
             components

          -  Whole Body Radiation Therapy (WBRT) is not allowed while patients receive IT
             trastuzumab/pertuzumab; however, focal stereotactic or palliative RT is allowed

          -  Significant medical or psychiatric illness that would interfere with compliance and
             ability to tolerate treatment as outlined in the protocol
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Maximum Tolerated Dose (MTD) of Intrathecal (IT) pertuzumab in combination with IT trastuzumab
Time Frame:Up to 12 weeks per dosing cohort
Safety Issue:
Description:MTD will be determined by testing increasing doses or pertuzumab beginning at 10 mg increasing to 20 mg, 40 mg and 80 mg, along with a fixed dose of 80 mg Trastuzumab.

Secondary Outcome Measures

Measure:Response Rate
Time Frame:Up to 1 year
Safety Issue:
Description:All patients included in the study will be assessed for response to treatment. Each patient will be assigned one of the following categories: 1) Complete Response,2) Partial Response, 3) Stable Disease, 4) Progressive Disease, 5) Early death due to disease, 6) Early death due to toxicity 7)Early death due to unknown cause. Participants in categories 4 through 6 would be considered as failing to respond to treatment.
Measure:Progression Free Survival (PFS)
Time Frame:Up to 1 year
Safety Issue:
Description:PFS measured from the date of first treatment to the date of first observation of Progressive Disease (PD), nonreversible neurologic progression, or death due to any cause

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Last Updated

October 8, 2020