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Mirvetuximab Soravtansine (IMGN853), in Folate Receptor Alpha (FRα) High Recurrent Ovarian Cancer (MIROVA)

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ClinicalTrials.gov Identifier: NCT04274426
Recruitment Status : Not yet recruiting
First Posted : February 18, 2020
Last Update Posted : February 18, 2020
Sponsor:
Information provided by (Responsible Party):
AGO Research GmbH

Brief Summary:
This is a multi-center, randomized, two-arm, open-label, comparative phase II trial of Mirvetuximab soravtansine (IMGN853), in folate receptor alpha (FRα) high recurrent ovarian cancer eligible for platinum-based chemotherapy.

Condition or disease Intervention/treatment Phase
Recurrent Epithelial Ovarian, Fallopian or Peritoneal Carcinoma Drug: Carboplatin Drug: Pegylated liposomal doxorubicin (PLD) Drug: Gemcitabine Drug: Paclitaxel Drug: Mirvetuximab Soravtansine Phase 2

Detailed Description:

136 patients will be randomized into the follow-ing two treatment arms as specified below:

Arm A: Control arm Platinum-based chemotherapy Arm B: Carboplatin + Mirvetuximab soravtansine (IMGN853)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 136 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Mirvetuximab Soravtansine (IMGN853), in Folate Receptor Alpha (FRα) High Recurrent Ovarian Cancer Eligible for Platinum-based Chemotherapy.
Estimated Study Start Date : July 2020
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2023


Arm Intervention/treatment
Active Comparator: Control arm with Platinum-based chemotherapy
  1. Carboplatin (AUC5, d1) as monotherapy q21d
  2. Carboplatin (AUC5, d1) combined with pegylated liposomal doxorubicin (PLD) (30 mg/m², d1) q28d
  3. Carboplatin (AUC4, d1) combined with gemcitabine (1000 mg/m2, d1 & d8) q21d
  4. Carboplatin (AUC5, d1) combined with paclitaxel (175 mg/m², d1) q21d
Drug: Carboplatin
Carboplatin will administered by intravenous route

Drug: Pegylated liposomal doxorubicin (PLD)
PLD will be administered by intravenous route

Drug: Gemcitabine
Gemcitabine will be administered by intravenous route

Drug: Paclitaxel
Paclitaxel will be administered by intravenous route

Experimental: Carboplatin + Mirvetuximab soravtansine (IMGN853)
Carboplatin (AUC5, d1) + Mirvetuximab soravtansine (IMGN853) 6 mg/kg IV d1 x 6 cycles q21d, followed by subsequent monotherapy of Mirvetuximab soravtansine (IMGN853) 6 mg/kg IV q3w until disease progression.
Drug: Carboplatin
Carboplatin will administered by intravenous route

Drug: Mirvetuximab Soravtansine
Mirvetuximab Soravtansine will be administered by intravenous route




Primary Outcome Measures :
  1. Progression free survival (PFS) defined as the time from randomization to progressive disease (PD) or death, whichever occurs earlier. PD is based on investigator assess-ment using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). [ Time Frame: Up to 2.5 years. From date of randomization until date of progressive disease (PD) or death, whichever occurs earlier. ]
    PD is based on investigator assessment using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).


Secondary Outcome Measures :
  1. OS [ Time Frame: Up to 2.5 years. From date of randomization until date of death from any cause. ]
    Overall survival

  2. ORR [ Time Frame: Up to 2.5 years. From date of randomization to date of death death from any cause. ]
    Objective response rate

  3. Efficacy regarding PFS [ Time Frame: Up to 2.5 years. From date of randomization to date of death from any cause. ]
    Efficacy regarding Progression Free Survival depending on histologic subtype

  4. Efficacy regarding OS [ Time Frame: Up to 2.5 years. From date of randomization to date of death from any cause. ]
    Efficacy regarding Overall Survival depending on histologic subtype

  5. Efficacy regarding ORR [ Time Frame: Up to 2.5 years. From date of randomization to date of death from any cause. ]
    Efficacy regarding Objective Response Rate depending on histologic subtype

  6. Serological progressive disease [ Time Frame: Up to 2.5 years. From date of randomization to date of death death from any cause. ]
    Time to serological progressive disease according to GCIG criteria

  7. Time to first subsequent treatment (TFST) [ Time Frame: Up to 2.5 years. From date of randomization to date of death from any cause. ]
    Time to first subsequent treatment (TFST)

  8. Time to second subsequent treatment (TSST) [ Time Frame: Up to 2.5 years. From date of randomization until date of death from any cause. ]
    Time to second subsequent treatment (TSST)

  9. Patient-reported outcomes [ Time Frame: Up to 2.5 years. From date of randomization until date of death from any cause. ]
    Quality of Life (EORTC C-30)

  10. Patient-reported outcomes [ Time Frame: Up to 2.5 years. From date of randomization until date of death from any cause. ]
    Quality of Life (EORTC OV28)

  11. Safety and tolerability [ Time Frame: Up to 2.5 years. From date of randomization until date of death from any cause through study completion. ]
    Safety and tolerability of the used drugs evaluated by NCI CTCAE v5.0



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:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. All patients must have a pathologically documented, definite diagnosis of epithelial cancer of the ovary, the fallopian tube or the peritoneum
  2. Relapsed disease with a platinum-free interval >3 months
  3. All histologic subtypes of ovarian carcinoma including carcinosarcoma (malignant mixed Mullerian tumors, MMMT)
  4. Patients with wildtype BRCA1/2 mutation status or with a deleterious BRCA1/2 mutation in germline or somatic testing if they underwent PARP inhibitor therapy in previous treatment line.
  5. Patients must be willing to provide archival tumor tissue from current relapse or previous surgeries/biopsies for central confirmation of FRα high status by PS2+ scoring:

    all tumors must exhibit ≥75% of tumor cells with FRα membrane staining and ≥ 2+ intensity by immunohistochemistry (IHC) using the Ventana FOLR1 (FOLR1 2.1) CDx assay.

  6. Patients must have measurable disease or evaluable disease in combination with GCIG CA-125 criteria.
  7. Patients had one or more prior lines of chemotherapy. The last line of chemotherapy should have included platinum and has resulted in a partial or complete response.
  8. Major surgery (not including placement of vascular access device, tumor punch/scrape biopsies or secondary wound closure) must be completed four weeks prior to Day 1.
  9. Patients must have adequate hematological, liver, cardiac and kidney function:

    1. Hemoglobin ≥ 10.0 g/dL.
    2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    3. Platelet count ≥ 100 x 109/L.
    4. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
    5. Aspartate aminotransferase/Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT)) and Alanine aminotransferase/Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) ≤ 2.5 x ULN, unless liver metastases are present in which case they must be ≤ 5 x ULN.
    6. Serum creatinine ≤ 1.5 x institutional ULN and glomerular filtration rate of at least 40 ml/minute according to Cockroft-Gault formula.
  10. Patient is female and ≥18 years of age at the time of the first screening visit.
  11. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
  12. Patients must be willing and able to sign the informed consent form, and to adhere to the study visit schedule and other protocol requirements.
  13. For women of childbearing potential (a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) must use a highly effective method of contraception. Such methods include:

    1. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

      • oral
      • intravaginal
      • transdermal
    2. Progestogen-only hormonal contraception associated with inhibition of ovula-tion:

      • oral
      • injectable
      • implantable
    3. Intrauterine device (IUD)
    4. Intrauterine hormone-releasing system (IUS)
    5. Bilateral tubal occlusion
    6. Vasectomized partner
    7. Sexual abstinence

Exclusion Criteria:

  1. Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors)
  2. Ovarian tumors of low malignant potential (e.g. borderline tumors).
  3. Unknown BRCA status.
  4. Patients who are planned to receive bevacizumab for the current relapse.
  5. Other malignancy within the last 3 years (except cervix or breast in situ carcinoma, type I stage I endometrial cancer)
  6. Patients who underwent surgery for the current relapse with macroscopic complete resection
  7. Prior systemic anticancer therapy within 28 days before randomization
  8. Prior treatment with folate receptor-targeting investigational agents is not allowed.
  9. Patients with > Grade 1 peripheral neuropathy.
  10. Serious concurrent illness or clinically-relevant active infection
  11. Previous clinical diagnosis of non-infectious interstitial lung disease, including non-infectious pneumonitis.
  12. Active or chronic corneal disorders such as 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 uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, and /or monocular vision. Active or chronic corneal disorder
  13. Required use of folate-containing supplements (e.g. folate deficiency)
  14. Women of childbearing potential (WOCBP) not protected by highly effective contraceptive methods.
  15. Pregnant and/or breast-feeding women.
  16. Known hypersensitivity to Carboplatin.

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): NCT04274426


Contacts
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Contact: Michaela Fredrich +49 611 880467 ext 42 mfredrich@ago-oavr.de

Locations
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Sponsors and Collaborators
AGO Research GmbH
Additional Information:
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Responsible Party: AGO Research GmbH
ClinicalTrials.gov Identifier: NCT04274426    
Other Study ID Numbers: AGO-OVAR 2.34
2018-004207-39 ( EudraCT Number )
First Posted: February 18, 2020    Key Record Dates
Last Update Posted: February 18, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Gemcitabine
Paclitaxel
Maytansine
Carboplatin
Doxorubicin
Liposomal doxorubicin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors