Grapiprant and Eribulin for the Treatment of Metastatic Inflammatory Breast Cancer

  • STATUS
    Recruiting
  • End date
    Dec 31, 2025
  • participants needed
    25
  • sponsor
    M.D. Anderson Cancer Center
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Updated on 10 July 2022
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Summary

This phase Ib/II trial tests the safety and side effects of grapiprant and eribulin and whether they work to shrink tumors in patients with inflammatory breast cancer that has spread to other places in the body (metastatic). Grapiprant is an anti-inflammatory drug that may prevent tumor growth. Eribulin may block tumor cell growth by stopping tumor cell division. Giving grapiprant and eribulin together may help to control the disease.

Description

PRIMARY OBJECTIVE:

I. To determine the safety and efficacy of grapiprant and eribulin combination treatment for the patient with metastatic inflammatory breast cancer (mIBC).

SECONDARY OBJECTIVES:

I. To determine objective response rate (ORR), % of the patients who achieve complete response (CR) or partial response (PR).

II. To determine the time to progression (TTP) of the proposed treatment. III. To determine the duration of response of the proposed treatment. (Phase 2 only) IV. To determine the time to first response of the proposed treatment. (Phase 2 only) V. To determine progression-free survival (PFS) of the proposed treatment. VI. To determine the overall survival (OS) of the proposed treatment. VII. To investigate the predictive biomarker of the proposed treatment.

EXPLORATORY OBJECTIVE:

I. To evaluate the changes in the tumor microenvironment after the proposed treatment.

OUTLINE

Patients receive grapiprant orally (PO) twice daily (BID) on day 1-21 and eribulin mesylate intravenously (IV) over 5 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then yearly for up to 5 years.

Details
Condition Breast Inflammatory Carcinoma, Recurrent Breast Inflammatory Carcinoma, Stage IV Breast Inflammatory Carcinoma
Treatment Eribulin mesylate, grapiprant
Clinical Study IdentifierNCT05041101
SponsorM.D. Anderson Cancer Center
Last Modified on10 July 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

Male or female >= 18 years of age
Is willing and able to provide written informed consent for the trial
Has histological confirmation of breast carcinoma with a clinical diagnosis of IBC based on the presence of inflammatory changes in the involved breast, including diffuse erythema and edema (peau d'orange), with or without an underlying palpable mass involving the majority of the skin of the breast. Or the diagnosis confirmed by the MD Anderson IBC specialists. Pathological evidence of dermal lymphatic invasion should be noted but is not required for the diagnosis of IBC
Any prior treatments will be allowed except eribulin and/or any EP2/4 inhibitor
Has at least 2 weeks of untreated period from the previous treatment
Any receptor status for ER/PR and HER2. But for HER2+ type, must has failed trastuzumab, pertuzumab, and T-DM1 treatment
NOTE: HER2 positive status is defined as strongly positive (3+) staining score by immunohistochemistry (IHC), or gene amplification using fluorescence in situ hybridization (FISH), if performed. If IHC is equivocal (2+). HER2 negative status, which is determined by assays using IHC require negative (0 or 1+) staining score. If IHC is equivocal (2+) staining score
Has a measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
version (v)1.1 (only applies to phase II part)
NOTE: Measurable disease: Measurable lesions are defined as those that can be accurately measured in at least one-dimension (longest diameter to be recorded) as >= 20 mm by chest X-ray, >= 10 mm by computed tomography (CT) scan, >= 10 mm with calipers by clinical exam. Measurable malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph node must be >= 15mm in short axis when assessed by CT scan. Non-measurable disease: All other lesions (or sites of disease), including small lesions, are considered non-measurable. Bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, lymphangitis, cutis/pulmonitis, inflammatory breast disease, and abdominal masses (not followed by CT or magnetic resonance imaging [MRI]) are considered non-measurable
Has a distant metastasis site or locoregional recurrence
Is willing to provide fresh tumor tissue via tumor biopsy before the first dose of the study drug only if participant has a disease can be be safely accessed through a CT-guided/ultrasound (US)-guided or percutaneous biopsy for multiple core biopsies judged by the investigator. If participant doesn't have a disease that can be safely accessed, they are still eligible
Performance status (PS) of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) performance scale
Absolute neutrophil count (ANC) >= 1,200 /mcL
Platelets >= 100,000 /mcL
Hemoglobin (Hgb) >= 9 g/dL
Total bilirubin =< 1.5 x upper limit of normal (ULN) (up to =< 3 x ULN for patients with liver metastasis)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (up to =< 5 x ULN for patients with liver metastasis)
Cockcroft-Gault glomerular filtration rate (GFR) (mL/min/1.73 m^2) >= 50
Left ventricular ejection fraction (LVEF) >= 50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
Female patients must not be pregnant or breastfeeding and must be practicing a medically acceptable form of locally approved birth control, be sterile or post-menopausal. Male patients should be using a medically acceptable form of birth control during the trial or be sterile
Female patient: A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions
applies
Not a woman of childbearing potential (WOCBP) OR
A WOCBP agrees to follow the contraceptive guidance during the treatment period and at least 6 months after the last dose of trial intervention and must refrain from breastfeeding for at least 2 months after the last grapiprant treatment
WOCPB must have a negative urine pregnancy test no more than 7 days prior to starting treatment on-study
Male patients: A male patient must agree to use contraception during the
With CD4+ T-cell (CD4+) counts >= 350 cells/uL
treatment period and for at least 6 months after the last grapiuprant
Without a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections
treatment and refrain from donating sperm during this period
Patient with human immunodeficiency virus (HIV) including current or prior infection
would be included if

Exclusion Criteria

Current chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors. We will allow prior use of those agents if patients stop them at least 2 weeks before accrual
Is currently participating in a study of an investigational anti-cancer agent or receiving concurrent anti-cancer therapy for metastatic disease
Has a diagnosis of immunodeficiency, or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy
Uncontrolled hypertension is defined as a systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg, with or without antihypertensive medications
Has a history of and/or active cardiac diseases
History of cardiac diseases including
Active myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular function
History of documented chronic heart failure; and documented cardiomyopathy
Active cardiac diseases including
Symptomatic angina pectoris within the past 180 days that required the initiation of or increase in anti-anginal medication or other intervention
Ventricular arrhythmias except for benign premature ventricular contractions
Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
Conduction abnormality requiring a pacemaker
Valvular disease with documented compromise in cardiac function
Symptomatic pericarditis
Has preexisting neuropathy > grade 2
Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative
Has medical conditions requiring concomitant administration of strong CYP3A4 or P-glycoprotein inhibitors or inducers
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate if they are stable and have no evidence of new or enlarging brain metastases. They are not using steroids for at least 28 days before trial treatment
Active infection requiring systemic therapy
Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
Known active hepatitis B or C
Potentially life-threatening second malignancy requiring systemic treatment within the last 3 years (i.e., patients with a history of prior malignancy are eligible if treatment was completed at least 3 years before entering the Treatment period and the patient has no evidence of disease) or which would impede evaluation of treatment response
Hormone ablation therapy is allowed within the last 3 years
Patients with history of prior early stage basal/squamous cell skin cancer or non-invasive or in situ cancers that have undergone definitive treatment at any time are eligible
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