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Grapiprant and Eribulin for the Treatment of Metastatic Inflammatory Breast Cancer

Primary Purpose

Breast Inflammatory Carcinoma, Recurrent Breast Inflammatory Carcinoma, Stage IV Breast Inflammatory Carcinoma

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Eribulin Mesylate
Grapiprant
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Inflammatory Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 treatment period and for at least 6 months after the last grapiuprant treatment and refrain from donating sperm during this period
  • Patient with human immunodeficiency virus (HIV) including current or prior infection would be included if:

    • With CD4+ T-cell (CD4+) counts >= 350 cells/uL
    • Without a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections

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
  • 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.
  • 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

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (grapiprant, eribulin mesylate)

Arm Description

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

Outcomes

Primary Outcome Measures

Incidence of dose-limiting toxicity
Clinical benefit rate (CBR)
Defined as complete response (CR) + partial response (PR) + stable response (> 24 weeks). The CBR will be summarized by frequency and percentage with 95% exact confidence intervals for all patients and by doses.

Secondary Outcome Measures

Full Information

First Posted
September 2, 2021
Last Updated
May 24, 2023
Sponsor
M.D. Anderson Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT05041101
Brief Title
Grapiprant and Eribulin for the Treatment of Metastatic Inflammatory Breast Cancer
Official Title
Phase Ib/II Study of Grapiprant (IK-007) and Eribulin Combination Treatment for Metastatic Inflammatory Breast Cancer (mIBC)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 4, 2021 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Inflammatory Carcinoma, Recurrent Breast Inflammatory Carcinoma, Stage IV Breast Inflammatory Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (grapiprant, eribulin mesylate)
Arm Type
Experimental
Arm Description
Patients receive grapiprant PO BID on day 1-21 and eribulin mesylate IV over 5 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Eribulin Mesylate
Other Intervention Name(s)
B1939 Mesylate, E7389, ER-086526, Halaven, Halichondrin B Analog
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Grapiprant
Other Intervention Name(s)
AAT-007, AT-001, CJ 023,423, CJ-023,423, CJ023,423, RQ-00000007, RQ-07
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Incidence of dose-limiting toxicity
Time Frame
Up to 21 days
Title
Clinical benefit rate (CBR)
Description
Defined as complete response (CR) + partial response (PR) + stable response (> 24 weeks). The CBR will be summarized by frequency and percentage with 95% exact confidence intervals for all patients and by doses.
Time Frame
Up to 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 treatment period and for at least 6 months after the last grapiuprant treatment and refrain from donating sperm during this period Patient with human immunodeficiency virus (HIV) including current or prior infection would be included if: With CD4+ T-cell (CD4+) counts >= 350 cells/uL Without a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections 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 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. 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sadia Saleem
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center

Learn more about this trial

Grapiprant and Eribulin for the Treatment of Metastatic Inflammatory Breast Cancer

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