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

• ClinicalTrials.gov Identifier: NCT04647916
• Recruitment Status: Recruiting
• First Posted: December 1, 2020
• Last Update Posted: August 14, 2023
• Sponsor: SWOG Cancer Research Network
• Collaborators: National Cancer Institute (NCI); Gilead Sciences
• Information provided by (Responsible Party): SWOG Cancer Research Network

Tracking Information

• First Submitted Date: November 23, 2020
• First Posted Date: December 1, 2020
• Last Update Posted Date: August 14, 2023
• Actual Study Start Date: June 8, 2021
• Estimated Primary Completion Date: February 17, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 23, 2020)

Objective response rate (ORR) [ Time Frame: Up to 2 years ]

ORR will be evaluated using use a Simon two-stage minimax design.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 23, 2020)

• Overall survival [ Time Frame: From date of registration to date of death due to any cause, assessed up to 2 years ]
  Will use the Kaplan-Meier curves to estimate the respective survival curves.
• 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 ]
  Will use the Kaplan-Meier curves to estimate the respective survival curves.
• Incidence of adverse events [ Time Frame: Up to 2 years ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• Brief Summary: 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Intervention

Biological: Sacituzumab Govitecan

Given IV

Other Names:

• hRS7-SN38 Antibody Drug Conjugate
• IMMU-132
• RS7-SN38
• Sacituzumab Govitecan-hziy
• Trodelvy

Study Arms

Experimental: Treatment (sacituzumab govitecan)

Patients 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.

Intervention: Biological: Sacituzumab Govitecan

• Publications *: Kwapisz D. Sacituzumab Govitecan-hziy in Breast Cancer. Am J Clin Oncol. 2022 Jul 1;45(7):279-285. doi: 10.1097/COC.0000000000000919. Epub 2022 May 12.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 23, 2020): 44
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2026
• Estimated Primary Completion Date: February 17, 2025 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Alicia Aranda; 210-614-8808; aaranda@swog.org

Contact: Dana Sparks; 210-614-8808; dsparks@swog.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04647916
• Other Study ID Numbers: S2007; NCI-2020-07706 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); S2007 ( Other Identifier: SWOG ); S2007 ( Other Identifier: CTEP ); U10CA180888 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: SWOG Cancer Research Network
• Original Responsible Party: Same as current
• Current Study Sponsor: SWOG Cancer Research Network
• Original Study Sponsor: Same as current

Collaborators

• National Cancer Institute (NCI)
• Gilead Sciences

Investigators

• Principal Investigator: Andrew J Brenner; SWOG Cancer Research Network

• PRS Account: SWOG Cancer Research Network
• Verification Date: August 2023