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Trial record 2 of 14 for:    monalizumab

Monalizumab and Trastuzumab In Metastatic HER2-pOSitive breAst Cancer: MIMOSA-trial (MIMOSA)

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ClinicalTrials.gov Identifier: NCT04307329
Recruitment Status : Recruiting
First Posted : March 13, 2020
Last Update Posted : April 21, 2021
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
The Netherlands Cancer Institute

Brief Summary:
In this phase II clinical trial the efficacy of the combination of monalizumab and trastuzumab is assessed in patients with metastatic or locally incurable HER2-positive breast cancer

Condition or disease Intervention/treatment Phase
Breast Cancer Biological: Monalizumab Biological: Trastuzumab Phase 2

Detailed Description:

In this phase II clinical trial with an explorative nature, the efficacy of the combination of monalizumab and trastuzumab is assessed in patients with metastatic or locally incurable HER2-positive breast cancer. Clinical efficacy will be assessed in patients with high stromal tumor-infiltrating lymphocytes (sTILs) or low sTILs in two separate cohorts (higher or equal to 5% versus lower than 5%). Since the combination of monalizumab and trastuzumab has not been administered before, dose limiting toxicities (DLTs) will be monitored throughout the trial using the Pocock-type boundary rules for continuous monitoring of toxicity in phase II trials.

In the first stage, 11 patients will be accrued per cohort. If there are 1 or fewer responses in these 11 patients, the study will be stopped. Otherwise, 8 additional patients will be accrued for a total of 19 patients.

The study will start with two cohorts (sTILs high and sTILs low), a total of 22 (2x11) patients will be included in the first stage. Dependent on the interim analysis (continuation of no cohorts, 1 or 2 cohorts), a maximum of 38 patients will be included.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Simon's two-stage minimax design
Masking: None (Open Label)
Masking Description: Two cohorts; high TILs (≥ 5%) and low (< 5%) TILs
Primary Purpose: Treatment
Official Title: Monalizumab and Trastuzumab In Metastatic HER2-pOSitive breAst Cancer: MIMOSA-trial
Actual Study Start Date : March 23, 2021
Estimated Primary Completion Date : May 1, 2023
Estimated Study Completion Date : May 1, 2030

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Trastuzumab

Arm Intervention/treatment
Experimental: Monalizumab + trastuzumab - low TILs (<5%)
trastuzumab 4 mg/kg and monalizumab 750 mg every two weeks.
Biological: Monalizumab
Monalizumab 750 mg every two weeks

Biological: Trastuzumab
Trastuzumab 4 mg/kg every two weeks

Experimental: Monalizumab + trastuzumab - high TILs (>=5%)
trastuzumab 4 mg/kg and monalizumab 750 mg every two weeks.
Biological: Monalizumab
Monalizumab 750 mg every two weeks

Biological: Trastuzumab
Trastuzumab 4 mg/kg every two weeks




Primary Outcome Measures :
  1. Response [ Time Frame: to be assessed up to 120 months ]
    number of patients with partial response or complete response according to RECIST1.1


Secondary Outcome Measures :
  1. Clinical Benefit [ Time Frame: to be assessed every 8 weeks up to 120 months ]
    number of patients with complete response, partial response or stable disease for more than 24 weeks according to RECIST1.1

  2. Progression Free Survival [ Time Frame: assessed up to 120 months ]
    From date of registration until date of first documented progression or date of death, which ever comes first

  3. Overall survival [ Time Frame: assessed up to 120 months ]
    From date of registration until date of death

  4. Toxicity; incidence of toxicity [ Time Frame: assessed every 2 weeks until 30 days after last study treatment ]
    Adverse events will be graded according to NCI Common Toxicity Criteria version 5.0



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

without SISH amplification) breast cancer. HER2-positivity must have been assessed on a metastatic lesion.

  • Histological or cytological confirmed locally incurable or metastatic disease
  • Accessible lesion for study biopsies.
  • Administration of at least one line of palliative treatment with documented progression and a maximum of three lines of palliative chemotherapy in combination with HER2 targeting agents (TDM-1 is considered one line of palliative treatment). Trastuzumab in combination with endocrine treatment is not defined as one line of treatment.
  • Documented progression during previous trastuzumab-based therapy
  • Measurable disease according to RECIST1.1 (at least one target lesion)
  • Left ventricular ejection fraction of 50% or higher
  • WHO performance status of 0 or 1
  • No signs of a visceral crisis
  • Signed written informed consent - Subjects with brain metastases are eligible if they have been treated, asymptomatic and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks prior to study registration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration

Exclusion Criteria:

  • uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris
  • known leptomeningeal disease localization
  • history of having received other anticancer therapies within 2 weeks of start of the study drug
  • history of immunodeficiency, autoimmune disease, conditions requiring innmunosuppression (>10 mg daily prednisone equivalents) or chronic infections. Subjects with vitiligo, diabetes mellitus type I on a stable insulin regimen, psoriasis not requiring systemic treatment or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections will not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement, Sjogren's syndrome or conditions not expected to recur in the absence of an external trigger will not be excluded from the study. Adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoinnmune disease
  • prior treatment with immune checkpoint blockade or other forms of imnnunotherapy, such as but not limited to: anti-PD-(L)1, anti-PD-L2, anti-CTLA-4, anti-GITR or CD137/0X40 agonists
  • prior treatment with HER2-based vaccines
  • live vaccine within two weeks prior to start of the study, at any time during the study or within 5 months following the last dose of monalizumab. Inactivated vaccines, such as the seasonal flu vaccination, are allowed
  • history of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association functional classification .3), angina, myocardial infarction within 12 months prior to study treatment or ventricular arrhythmia.
  • active other cancer
  • positive test for hepatitis B surface virus surface antigen (HBsAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
  • allogeneic stem cell or organ transplantation, HIV or active tuberculosis
  • history of uncontrolled serious medical or psychiatric illness
  • Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  • current pregnancy or breastfeeding. Women of childbearing potential (WOCBP) must use adequate contraceptive protection. WOCBP must have a negative serum or urine pregnancy test

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04307329


Contacts
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Contact: Marleen Kok, MD +3120512 ext 9111 m.kok@nki.nl
Contact: Ingrid Mandjes, MSc +3120512 ext 9111 i.mandjes@nki.nl

Locations
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Netherlands
NKI-AVL Recruiting
Amsterdam, Netherlands
Contact: Marleen Kok, MD         
Principal Investigator: Marleen Kok, MD         
Sponsors and Collaborators
The Netherlands Cancer Institute
AstraZeneca
Investigators
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Principal Investigator: Marleen Kok, MD NKI-AvL
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Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT04307329    
Other Study ID Numbers: N19MIM
First Posted: March 13, 2020    Key Record Dates
Last Update Posted: April 21, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: to be detemined

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by The Netherlands Cancer Institute:
HER2 positive
Metastatic disease
Accessible lesion for study biopsies
Min 1, max 3 lines palliative treatment
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents