Clinical Trials /

Testing Sacituzumab Govitecan Therapy in Patients With HER2-Negative Breast Cancer and Brain Metastases

NCT04647916

Description:

This phase II trial studies the effect of sacituzumab govitecan in treating patients with HER2-negative breast cancer that has spread to the brain (brain metastases). Sacituzumab govitecan is a monoclonal antibody, called sacituzumab, linked to a chemotherapy drug, called govitecan. Sacituzumab is a form of targeted therapy because it attaches to specific molecules on the surface of cancer cells, known as Trop-2 receptors, and delivers govitecan to kill them. Giving sacituzumab govitecan may shrink the cancer in the brain and/or extend the time until the cancer gets worse.

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Testing Sacituzumab Govitecan Therapy in Patients With HER2-Negative Breast Cancer and Brain Metastases
  • Official Title: A Phase II Trial of Sacituzumab Govitecan (IMMU-132) (NSC #820016) for Patients With HER2-Negative Breast Cancer and Brain Metastases

Clinical Trial IDs

  • ORG STUDY ID: S2007
  • SECONDARY ID: NCI-2020-07706
  • SECONDARY ID: S2007
  • SECONDARY ID: S2007
  • SECONDARY ID: U10CA180888
  • NCT ID: NCT04647916

Conditions

  • Anatomic Stage IV Breast Cancer AJCC v8
  • Invasive Breast Carcinoma
  • Metastatic HER2 Negative Breast Carcinoma
  • Metastatic Malignant Neoplasm in the Brain
  • Prognostic Stage IV Breast Cancer AJCC v8

Interventions

DrugSynonymsArms
Sacituzumab GovitecanhRS7-SN38 Antibody Drug Conjugate, IMMU-132, RS7-SN38, Sacituzumab Govitecan-hziy, TrodelvyTreatment (sacituzumab govitecan)

Purpose

This phase II trial studies the effect of sacituzumab govitecan in treating patients with HER2-negative breast cancer that has spread to the brain (brain metastases). Sacituzumab govitecan is a monoclonal antibody, called sacituzumab, linked to a chemotherapy drug, called govitecan. Sacituzumab is a form of targeted therapy because it attaches to specific molecules on the surface of cancer cells, known as Trop-2 receptors, and delivers govitecan to kill them. Giving sacituzumab govitecan may shrink the cancer in the brain and/or extend the time until the cancer gets worse.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To evaluate the intracranial objective response rate (ORR) (complete response [CR] or
      partial response [PR] by Response Assessment in Neuro-Oncology Brain Metastases [RANO-BM])
      with sacituzumab govitecan (IMMU-132) in patients with HER2-negative metastatic breast cancer
      with brain involvement.

      SECONDARY OBJECTIVES:

      I. To evaluate bi-compartmental progression-free survival in this population. II. To evaluate
      overall survival in this population. III. To assess safety and tolerability of sacituzumab
      govitecan (IMMU-132) treatment in this population.

      IV. To evaluate ORR by hormone-receptor (HR) subgroup (HR+, HR-).

      BANKING OBJECTIVE:

      I. To bank specimens for future correlative studies.

      OUTLINE:

      Patients receive sacituzumab govitecan intravenously (IV) over 1-3 hours on days 1 and 8.
      Cycles repeat every 21 days for up to 2 years in the absence of disease progression or
      unacceptable toxicity.

      After completion of study registration, patients are followed up every 3 months for 1 year
      and then every 6 months for 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (sacituzumab govitecan)ExperimentalPatients receive sacituzumab govitecan IV over 1-3 hours on days 1 and 8. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
  • Sacituzumab Govitecan

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have histologically confirmed HER2-negative (per 2018 American
             Society of Clinical Oncology [ASCO]/College of American Pathologists [CAP] joint
             guideline) invasive breast cancer that has metastasized to the brain. NOTE: Pathology
             report must confirm HER2-negative invasive breast cancer. Brain metastases must be
             confirmed by radiology report

          -  Participants must have an magnetic resonance imaging (MRI) of the brain within 28 days
             prior to registration and must have central nervous system metastases with at least
             one measurable brain metastasis >= 1.0 cm in size (per RANO-BM) that has not been
             irradiated, or has progressed despite prior radiation therapy (in the opinion of the
             treating physician). In the rare case that a previously irradiated brain metastasis is
             the sole target lesion and if there is concern about possible radiation necrosis,
             patient is eligible only if there is clear progression in the previously radiated
             lesion. Computed tomography (CT) of the head cannot substitute for brain MRI. All
             central nervous system (CNS) disease must be assessed and documented on the S2007
             Brain Metastases Baseline Tumor Assessment Form

          -  Participants may have measurable or non-measurable extracranial disease. All
             measurable disease must be assessed within 28 days prior to registration; all
             non-measurable disease must be assessed within 42 days prior to registration.
             Participants are NOT required to have extracranial disease, but must have scans done
             to document disease status at baseline. All extracranial disease must be assessed and
             documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in
             Solid Tumors [RECIST] 1.1). NOTE: Brain lesions should not be included on the Baseline
             Tumor Assessment Form (RECIST 1.1) for this study

          -  Participants must have had CNS progression after previous CNS-directed therapy
             (radiation therapy, surgery, or any combination of therapy)

          -  Participants must have resolution of adverse event(s) of the most recent prior
             systemic anti-cancer therapy to < grade 2, with the exception of alopecia and =< grade
             2 neuropathy, which are allowed

          -  Participants with a prior or concurrent malignancy whose natural history or treatment
             (in the opinion of the treating physician) does not have the potential to interfere
             with the safety or efficacy assessment of the investigational regimen are eligible for
             this trial

          -  Participants must have Zubrod performance status 0 or 1

          -  Participants must have history and physical exam obtained within 21 days prior to
             registration

          -  Absolute neutrophil count (ANC) >= 1,500/mcL (obtained within 21 days prior to
             registration)

          -  Platelet count >= 100,000/mcL (obtained within 21 days prior to registration)

          -  Hemoglobin >= 9.0 g/dL (obtained within 21 days prior to registration)

          -  Total bilirubin =< 1.5 times institutional upper limit of normal (ULN) (obtained
             within 21 days prior to registration)

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x
             institutional ULN (obtained within 21 days prior to registration)

          -  Participants must have a serum creatinine =< 1.5 times the institutional upper limit
             of normal (IULN) OR measured OR calculated creatinine clearance >= 30 mL/min using the
             following Cockcroft-Gault Formula. This specimen must have been drawn and processed
             within 21 days prior to registration

          -  Participants must have adequate cardiac function. Participants with known history or
             current symptoms of cardiac disease, or history of treatment with cardiotoxic agents,
             must have a clinical risk assessment of cardiac function using the New York Heart
             Association Functional Classification, and must be class 2B or better

          -  Participants must be offered the opportunity to participate in specimen banking. With
             participant consent, specimens must be collected and submitted via the Southwest
             Oncology Group (SWOG) Specimen Tracking System

          -  Participants must be informed of the investigational nature of this study and must
             sign and give informed consent in accordance with institutional and federal guidelines

        Exclusion Criteria:

          -  Participants must not have had more than 2 seizures within 28 days prior to
             registration

          -  Participants must not have received systemic therapy (including small-molecule kinase
             inhibitors) or non-cytotoxic hormonal therapy (e.g., tamoxifen) within 7 days prior to
             registration

          -  Participants must not have received anti-cancer biologic agents (antibodies, immune
             modulators, vaccines, cytokines) within 21 days prior to registration

          -  Participants must not have received nitrosoureas or mitomycin C within 42 days,
             metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxic
             chemotherapy within 28 days prior to registration

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             agents that are strong CYP3A4 inhibitors or inducers and who are unwilling or unable
             to change to antiretroviral therapies without such interactions are ineligible because
             of the potential for pharmacokinetic interactions with sacituzumab govitecan
             (IMMU-132)

          -  Due to potential drug interactions of anti-retroviral drugs with sacituzumab govitecan
             (IMMU-132), participants must not have known active or chronic hepatitis B virus (HBV)
             infection, requiring suppressive therapy or known active hepatitis C virus (HCV)
             infection. Participants with a known history of HCV infection must have been treated
             and cured

          -  Participants must not have received enzyme-inducing anti-epileptic agents (e.g.,
             carbamazepine, phenytoin, phenobarbital, primidone) within 7 days prior to
             registration or within 14 days of planned start of cycle 1, day 1 treatment, and
             participants must not be planning to receive enzyme-inducing anti-epileptic agents
             (e.g., carbamazepine, phenytoin, phenobarbital, primidone) for the duration of
             protocol treatment

          -  Participants must not be receiving warfarin (or other coumarin derivatives) at time of
             registration or be planning to receive warfarin (or other coumarin derivatives) for
             the duration of protocol treatment. Participants who are able to switch to low
             molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs) prior to date of
             registration (and plan to remain off of warfarin or other coumarin derivatives) for
             the duration of protocol treatment) are eligible

          -  Patients must not be receiving or be planning to receive concomitantly any other
             anti-cancer therapy, including endocrine therapy. Note: Concomitant hormone
             replacement therapy is allowed

          -  Participants must not have a condition requiring ongoing systemic treatment with
             corticosteroids (> 4 mg daily dexamethasone [or bioequivalent]) or other
             immunosuppressive medications within 7 days prior to the baseline MRI. Corticosteroids
             administration must be stable and planned to remain =< 4 mg daily for the duration of
             protocol treatment. However, use of corticosteroids for clinical symptoms is allowed
             based upon treating physician discretion

          -  Participants must not have uncontrolled diabetes in the opinion of the treating
             investigator 21 days prior to registration

          -  Participants must not be pregnant or nursing. Women of reproductive potential must
             have a negative serum or urine pregnancy test within 7 days prior to registration.
             Women and men of reproductive potential must have agreed to use an effective
             contraceptive method for the duration of protocol treatment and for at least 6 months
             after the last dose of sacituzumab govitecan (IMMU-132). A woman is considered to be
             of "reproductive potential" if she has had menses at any time in the preceding 12
             consecutive months. In addition to routine contraceptive methods, "effective
             contraception" also includes heterosexual celibacy and surgery intended to prevent
             pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
             bilateral oophorectomy or bilateral tubal ligation. However, if at any point a
             previously celibate participant chooses to become heterosexually active during the
             time period for use of contraceptive measures outlined, he/she is responsible for
             beginning contraceptive measures
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:ORR will be evaluated using use a Simon two-stage minimax design.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:From date of registration to date of death due to any cause, assessed up to 2 years
Safety Issue:
Description:Will use the Kaplan-Meier curves to estimate the respective survival curves.
Measure:Progression-free survival
Time Frame:From date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause, assessed up to 2 years
Safety Issue:
Description:Will use the Kaplan-Meier curves to estimate the respective survival curves.
Measure:Incidence of adverse events
Time Frame:Up to 2 years
Safety Issue:
Description:Adverse events will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The incidence of adverse events will be reported. Toxicity will be by grade and attribution to treatment.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Southwest Oncology Group

Last Updated

February 25, 2021