Clinical Trials /

Mirvetuximab Soravtansine (IMG853) in Folate Receptor Alpha-expressing TNBC

NCT03045393

Description:

The main purpose of this study is to determine how 2 doses mirvetuximab soravtansine affects the amount and activity of folate receptor alpha proteins in tumor cells of patients who have completed standard neoadjuvant treatment and are scheduled to have their tumors surgically removed.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Mirvetuximab Soravtansine (IMG853) in Folate Receptor Alpha-expressing TNBC
  • Official Title: Pilot Study of Mirvetuximab Soravtansine (IMGN853) in Folate Receptor Alpha (FRα)-Expressing, Triple Negative Breast Cancer (TNBC) With Residual Disease Post Standard Neoadjuvant Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: Pro00074621
  • NCT ID: NCT03045393

Conditions

  • Breast Cancer Triple Negative

Interventions

DrugSynonymsArms
Mirvetuximab Soravtansine (IMGN853)Mirvetuximab Soravtansine

Purpose

The main purpose of this study is to determine how 2 doses mirvetuximab soravtansine affects the amount and activity of folate receptor alpha proteins in tumor cells of patients who have completed standard neoadjuvant treatment and are scheduled to have their tumors surgically removed.

Detailed Description

      The folate receptor alpha protein is important in tumor growth and can be over-expressed in
      some tumor cells. The word "over-expressed" in this situation means that there are too many
      copies of the protein on the surface of the cell when compared to a healthy, normal cell,
      and this helps the tumor continue to grow in size. Mirvetuximab soravtansine acts by
      targeting the folate receptor in tumor cells. In animal models, mirvetuximab soravtansine is
      highly effective in decreasing tumor size. This suggests that mirvetuximab soravtansine may
      help shrink or stop growth of folate receptor alpha positive breast cancer in this study.

      In this study the investigator will be looking at how folate receptor alpha expression
      changes following 2 doses of neoadjuvant mirvetuximab soravtansine. The investigator will
      also look to evaluate the safety of this regimen, measure any change in tumor size,
      associate folate receptor alpha expression with a change in tumor size, and describe any
      changes in Ki-67 and percent of apoptotic cells in this population.
    

Trial Arms

NameTypeDescriptionInterventions
Mirvetuximab SoravtansineExperimentalParticipants will receive 2 doses of Mirvetuximab Soravtansine after neoadjuvant chemotherapy and before surgical resection of tumor.
  • Mirvetuximab Soravtansine (IMGN853)

Eligibility Criteria

        Screening Inclusion Criteria:

          -  Signed informed screening consent form with HIPAA authorization for release of
             personal health information.

          -  Research personnel will review medical records of subjects consenting to screening to
             ensure no obvious factors would exclude them from the treatment portion of the study
             (e.g., history of cirrhosis of the liver) and to confirm diagnosis and staging

          -  Histological confirmation of triple negative breast cancer (TNBC) biopsy report

          -  Stage 1-3 tumors > 1cm in maximal diameter.

          -  Standard neoadjuvant chemotherapy NAC and definitive surgery planned (NOTE: NAC
             chemotherapy will be per standard of care, and not dictated by this clinical trial)

          -  Must be able to supple sufficient tissue (block or slides) from diagnostic biopsy to
             undergo testing.

        Inclusion Criteria:

          -  Written informed consent and HIPAA authorization for release of personal health
             information.

          -  Must have operable tumor ≥ 1cm determined by and obtained less than 9 weeks after
             completion of standard NAC

          -  Must be able to meet study schedule: 2 doses of mirvetuximab soravtansine
             administered 3 weeks apart and surgery within 9 weeks of last dose of NAC.

          -  Willing to undergo biopsy for research purposes only (before and after), and to allow
             surgical tissue sample from surgery to be used for research purposes

          -  May have symptoms however must be ambulatory and able to carry out work of a light or
             sedentary nature (e.g., light housework, office work)

          -  Demonstrate adequate organ function through labs

          -  Females of childbearing years must have a negative serum pregnancy test within 48
             hours prior to dose 1 mirvetuximab soravtansine. NOTE: Sexually mature females are
             considered of child bearing potential unless they are surgically sterile (have
             undergone a hysterectomy, or bilateral oophorectomy) or they are naturally
             postmenopausal for at least 12 consecutive months

          -  Females of childbearing potential must be willing to abstain from heterosexual
             activity or to use two effective methods of contraception from the time of informed
             consent until 4 months after the last dose of mirvetuximab soravtansine

        Exclusion Criteria:

          -  Pregnant or breastfeeding, or plan to be pregnant within projected duration of the
             trial. (NOTE: breast milk cannot be stored for future use while the mother is being
             treated on study).

          -  Has a known additional malignancy that is active and/or progressive requiring
             treatment within 3 years of first dose.

          -  Prior treatment with mirvetuximab soravtansine

          -  Treatment with any investigational drug within 6 weeks of first clinical dose

          -  Subjects with > Grade 1 peripheral neuropathy

          -  Active or chronic corneal disorder, including but not limited to the following:

               -  Sjogren's syndrome

               -  Fuchs corneal dystrophy (requiring treatment)

               -  History of corneal transplantation

               -  Active herpetic keratitis

               -  Active ocular conditions requiring on-going treatment/monitoring such as wet
                  age-related macular degeneration requiring intravitreal injections, active
                  diabetic retinopathy with macular edema, presence of papilledema, and acquired
                  monocular vision.

          -  Serious concurrent illness or clinically-relevant active infection

          -  Cytomegalovirus infection

          -  Any concurrent infectious disease, requiring IV antibiotics within 2 weeks of first
             dose of mirvetuximab soravtansine

          -  Significant cardiac disease including

          -  History of neurological conditions that would confound assessment of
             treatment-emergent neuropathy other than ≤ Grade 1 peripheral neuropathy including
             multiple sclerosis or other demyelinating disease and/or eaton-lambert syndrome
             (para-neoplastic syndrome)" Diabetes is allowed.

          -  History of hemorrhagic or ischemic stroke within 6 months prior to first dose of
             mirvetuximab soravtansine

          -  History of cirrhotic liver disease

          -  Previous clinical diagnosis of non-infectious pneumonitis or non-infectious
             interstitial lung disease

          -  Prior hypersensitivity to monoclonal antibodies

          -  History or evidence of thrombotic or hemorrhagic disorders within 6 months prior to
             first dose of mirvetuximab soravtansine

          -  Required used of folate-containing supplements (e.g. for folate deficiency)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in breast tumor FRα expression before and after treatment with mirvetuximab soravtansine
Time Frame:Baseline up to 9 weeks
Safety Issue:
Description:Assessed by immunohistochemistry (IHC) (1) after completion of neoadjuvant chemotherapy, prior to treatment with mirvetuximab soravtansine; (2) at definitive surgery, after treatment with mirvetuximab soravtansine and scored (0 = no receptors, 1 = small number of receptors, 2 = medium number of receptors, 3 = large number of receptors).

Secondary Outcome Measures

Measure:Change in breast tumor FRα expression before and after neoadjuvant chemotherapy
Time Frame:Baseline up to 9 weeks
Safety Issue:
Description:Assessed by immunohistochemistry (IHC) (1) at initial cancer diagnosis, prior to initiation of neoadjuvant chemotherapy; (2) after completion of neoadjuvant chemotherapy and scored (0 = no receptors, 1 = small number of receptors, 2 = medium number of receptors, 3 = large number of receptors).
Measure:Total number of grade 3 and 4 toxicities
Time Frame:Baseline up to 9 weeks
Safety Issue:
Description:Graded via NCI CTCAE v4.03
Measure:Number of treatment-emergent adverse events (TEAEs) precluding second dose
Time Frame:Baseline up to 9 weeks
Safety Issue:
Description:Assessed by the number of subjects that cannot receive the second dose of mirvetuximab soravtansine
Measure:Number of treatment-emergent adverse events (TEAEs) delaying surgery
Time Frame:Baseline up to 9 weeks
Safety Issue:
Description:Assessed by the number of subjects that have surgery delayed past 9 weeks due to TEAE
Measure:Total number of partial or complete responses
Time Frame:Baseline up to 9 weeks
Safety Issue:
Description:Evaluated by the number of subjects that have either a partial or complete radiologic response by 2D ultrasound. (Partial response = reduction of the largest unidimensional tumor measurement of >30%; Complete response = no evidence of tumor remaining)
Measure:Change in tumor cell proliferation, as measured by Ki67 expression
Time Frame:Baseline up to 9 weeks
Safety Issue:
Description:Changes in Ki67 expression will be measured before and after 2 doses of mirvetuximab soravtansine.
Measure:Change in tumor cell death markers
Time Frame:Baseline up to 9 weeks
Safety Issue:
Description:Changes in apoptotic markers will be measured before and after 2 doses of mirvetuximab soravtansine.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Kimberly Blackwell

Trial Keywords

  • Neoadjuvant
  • Breast Cancer
  • Folate Receptor Alpha
  • FRa
  • TNBC
  • Triple Negative Breast Cancer
  • Preoperative
  • Presurgery
  • Mirvetuximab Soravtansine
  • IMGN853

Last Updated

April 30, 2017