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Safety and Efficacy of Tisotumab Vedotin in Combination With Other Cancer Agents in Subjects With Cervical Cancer

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ClinicalTrials.gov Identifier: NCT03786081
Recruitment Status : Recruiting
First Posted : December 24, 2018
Last Update Posted : August 14, 2019
Sponsor:
Collaborators:
Seattle Genetics, Inc.
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Belgian Gynaecological Oncology Group
Gynecologic Oncology Group
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Genmab

Brief Summary:

This is an open label, multi-center trial of tisotumab vedotin in combination with bevacizumab, pembrolizumab, or carboplatin in subjects with recurrent or stage IVB cervical cancer.

The trial consists of two-parts a dose escalation part and an expansion part. The expansion part of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) of the combinations have been determined in the dose escalation part.


Condition or disease Intervention/treatment Phase
Cervical Cancer Drug: Tisotumab Vedotin Drug: Bevacizumab Drug: Pembrolizumab Drug: Carboplatin Phase 1 Phase 2

Detailed Description:

The dose escalation part will occur in cervical cancer subjects who have progressed during or after standard of care therapy and who are intolerant or ineligible to receive standard of care treatments. Arm A will be conducted by escalating doses of both tisotumab vedotin and bevacizumab. Dose escalations of the tisotumab vedotin + pembrolizumab and tisotumab vedotin + carboplatin combinations (Arms B and C, respectively) will be conducted by combining fixed doses of either pembrolizumab or carboplatin with increasing doses of tisotumab vedotin.

The dose expansion part will consist of subjects with recurrent or stage IVB cervical cancer, who have not received prior systemic therapy for their recurrent or stage IVB disease, Arms D and E being treated with tisotumab vedotin + carboplatin or tisotumab vedotin + pembrolizumab, respectively, or subjects, who have progressed on or after standard of care treatments, Arm F treated with tisotumab vedotin + pembrolizumab. Subjects enrolled to these arms will receive the RP2D of tisotumab vedotin established in the dose escalation part.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Open-Label Trial of Tisotumab Vedotin (HuMax®-TF-ADC) in Combination With Other Agents in Subjects With Recurrent or Stage IVB Cervical Cancer
Actual Study Start Date : February 27, 2019
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cervical Cancer

Arm Intervention/treatment
Experimental: A: Tisotumab Vedotin + bevacizumab
Dose escalation: Tisotumab vedotin in combination with bevacizumab once every three weeks in previously treated patients
Drug: Tisotumab Vedotin
i.v.

Drug: Bevacizumab
i.v.
Other Name: Avastin

Experimental: B: Tisotumab vedotin + pembrolizumab
Dose escalation: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients
Drug: Tisotumab Vedotin
i.v.

Drug: Pembrolizumab
i.v.
Other Name: Keytruda

Experimental: C: Tisotumab vedotin + carboplatin
Dose escalation: Tisotumab vedotin in combination with carboplatin once every three weeks in previously treated patients
Drug: Tisotumab Vedotin
i.v.

Drug: Carboplatin
i.v.
Other Name: Paraplatin

Experimental: D: Tisotumab vedotin + carboplatin
Dose expansion:Tisotumab vedotin in combination with carboplatin once every three weeks in previously untreated patients
Drug: Tisotumab Vedotin
i.v.

Drug: Carboplatin
i.v.
Other Name: Paraplatin

Experimental: E: Tisotumab vedotin + pembrolizumab
Dose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously untreated patients
Drug: Tisotumab Vedotin
i.v.

Drug: Pembrolizumab
i.v.
Other Name: Keytruda

Experimental: F: Tisotumab vedotin + pembrolizumab
Dose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients
Drug: Tisotumab Vedotin
i.v.

Drug: Pembrolizumab
i.v.
Other Name: Keytruda




Primary Outcome Measures :
  1. Dose escalation: Dose Limiting Toxicities (DLTs) [ Time Frame: DLTs will be identified during the first treatment cycles (21 days cycles) ]
    To establish the MTD and RP2D of tisotumab vedotin in combination

  2. Dose expansion: Evaluate the antitumor activity of tisotumab vedotin in combination in subjects with cervical cancer [ Time Frame: approximately 2 years ]
    Objective Response Rate (ORR) based upon RECIST v1.1.


Secondary Outcome Measures :
  1. Adverse events (AEs) [ Time Frame: up to 2 years ]
    Frequency, duration, and severity of adverse events (AEs)

  2. Objective Response Rate [ Time Frame: approximately 2 years ]
    Objective Response Rate (ORR) based upon RECIST v1.1.

  3. Duration of Response [ Time Frame: approximately 2 years ]
    Duration of Response (DOR) based upon RECIST v1.1.

  4. Time to Response [ Time Frame: approximately 2 years ]
    Time to Response (TTR) based upon RECIST v1.1.

  5. Progression free survival [ Time Frame: approximately 2 years ]
    Progression free survival (PFS) based upon RECIST v1.1.

  6. Overall Survival [ Time Frame: approximately 2 years ]
    Overall Survival (OS)



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
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Patients with cervical cancer
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have squamous, adenosquamous, or adenocarcinoma of the cervix and progressed on or after standard of care treatments or are ineligible or intolerant to standard of care for recurrent or stage IVB cervical cancer (Arms A, B and C only).
  • Must have squamous, adenosquamous, or adenocarcinoma of the cervix and must not have received prior systemic therapy for recurrent or stage IVB cervical cancer (Arms D and E only).
  • Must have squamous, adenosquamous, or adenocarcinoma of the cervix and progressed on or after at least one but no more than two standard of care treatments for recurrent or stage IVB cervical cancer (Arm F only).
  • Must have baseline measurable disease per RECIST v1.1.
  • Must be at least 18 years of age on the day of signing informed consent (All Arms).
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (All Arms).
  • Is not pregnant, breastfeeding, or expecting to conceive children within the projected duration of the trial and for at least 6 months after the last trial treatment administration
  • Women of childbearing potential must agree to use adequate contraception during and for 6 months after the last dose of trial treatment administration.
  • Must sign an informed consent form (ICF) indicating the trial subject understands the purpose of and procedures required for the trial and are willing to participate in the trial (All Arms).

Exclusion Criteria:

  • Has clinically relevant bilateral hydronephrosis which cannot be alleviated by ureteral stents or percutaneous drainage. (All Arms)
  • Has clinical signs or symptoms of gastrointestinal obstruction and requires parenteral hydration and/or nutrition. Post-operative obstructions within 4 weeks of abdominal surgery are permitted. (All Arms)
  • Has clinically significant bleeding issues or risks
  • Prior history (within 3 months) or current evidence of hemoptysis (1/2 teaspoon or more) (Arm A only)
  • Recent (within 4 weeks of first dose of trial treatment) clinically significant gastrointestinal or vaginal bleeding requiring PRBC transfusion (Arm A only)
  • Recent (within 4 weeks of first dose of trial treatment) evidence of wound healing complications that require medical intervention (Arm A only)
  • Has active ocular surface disease at baseline. Subjects with prior history of cicatricial conjunctivitis are ineligible (All Arms).
  • Clinically significant cardiac disease
  • Requires anti-coagulation therapy

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): NCT03786081


Contacts
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Contact: Genmab A/S Trial Information +4570202728 clinicaltrials@genmab.com

Locations
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United States, California
Univ California, Irvine Medical Center Recruiting
Orange, California, United States, 92868
Contact: Sara Richards    714-509-9719    srichar4@uci.edu   
Principal Investigator: Krishnansu Tewari, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60525
Contact: Penny Dolan    773-702-3394    pdolan@babies.bsd.uchicago.edu   
Principal Investigator: John Moroney, MD         
United States, Kansas
University of Kansas Medical Center Recruiting
Westwood, Kansas, United States, 66205
Contact: James Jeffrey    913-945-7549    jjeffery2@kumc.edu   
Principal Investigator: Andrea Jewell, MD         
United States, Massachusetts
Dana Farber Recruiting
Boston, Massachusetts, United States, 02215
Contact: Victoria Engvold    617-632-2164    vengvold@partners.org   
Principal Investigator: Susanna Campos, MD         
United States, Montana
Montana Cancer Consortium Recruiting
Billings, Montana, United States, 59102
Contact: Kelsey Skogen    406-435-7443    kskogen@billingsclinic.org   
Principal Investigator: Benjamin Marchello, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Joyce Guillen    646-735-8278    guillenj@mskcc.org   
Principal Investigator: Roisin O'Cearbhaill, MD         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Claire Licina    216-445-5394    licinac@ccf.org   
Principal Investigator: Peter Rose, MD         
Ohio State University Wexner Medical Center Recruiting
Hilliard, Ohio, United States, 43026
Contact: Molly Myers    614-685-6411    Molly.Myers@osumc.edu   
Principal Investigator: David O'Malley, MD         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Brittney Cirone    215-214-1667    Brittney.Cirone@fccc.edu   
Principal Investigator: Christina Chu, MD         
United States, Rhode Island
Women's and Infant Hospital Recruiting
Providence, Rhode Island, United States, 02905
Contact: Janet Mari    401-274-1122 ext 48181    jmari@wihri.org   
Principal Investigator: Cara Mathews, MD         
Belgium
Cliniques universitaires Saint-Luc Recruiting
Brussels, Belgium, 1200
Contact: Louise Favaretto    +32 2 764 35 13    louise.favaretto@uclouvain.be   
Principal Investigator: Jean-Francois Baurain, MD         
Universitaire Ziekenhuizen Leuven, Recruiting
Leuven, Belgium
Contact: Bo Vantilt    +32 16 34 19 07    bo.vantilt@uzleuven.be   
Principal Investigator: Ignace Vergote, Prof         
Centre Hospitalier Universitaire de Liège Recruiting
Liège, Belgium, 4000
Contact: Maude Piron    +32 4 366 82 50    mpiron@chuliege.be   
Principal Investigator: Christine Gennigens, MD         
Denmark
Rigshospitalet Recruiting
Copenhagen, Denmark, 5072
Contact: Ane Taudorf Nørmark    +45 3545 6997    ane.taudorf.noermark.01@regionh.dk   
Principal Investigator: Mansoor Mirza, MD         
Sub-Investigator: Kristen Madsen, MD         
Ireland
Cork University Hospital Recruiting
Cork, Ireland
Contact: Edel Hassett    086-1728701    Edel.hassett@hse.ie   
Principal Investigator: Dearbhaile Collins, MD         
Mater Misericordiae University Hospital Active, not recruiting
Dublin, Ireland, D07 R2WY D
University Hospital Waterford Recruiting
Waterford, Ireland
Contact: Flordeliza Calacsan    +353 51 848590    Flordeliza.calacsan@hse.ie   
Principal Investigator: Paula Calvert, MD         
Netherlands
AMC Medical Research Recruiting
Amsterdam, Netherlands
Contact: Eva VanDalen       trialmedonc@amc.uva.nl   
Contact: Lyda ter Hofstede       trialmedonc@amc.uva.nl   
Principal Investigator: Anneke Westermann, MD         
Universitair Medisch Centrum Groningen (UMCG) Recruiting
Groningen, Netherlands, 9713
Contact: B.T. Smit-Aeikema    +31 50 361 3919    b.t.smit@umcg.nl   
Principal Investigator: An Reyners, MD         
Radboudumc Active, not recruiting
Nijmegen, Netherlands, 6525 GA
Erasmus University Medical Center Rotterdam Recruiting
Rotterdam, Netherlands, 3015
Contact: Cindy Bolder    +310107034897    c.bolder@erasmusmc.nl   
Principal Investigator: Ingrid Boere, MD         
University Medical Center Utrecht (UMC Utrecht) Recruiting
Utrecht, Netherlands, 3584
Contact: Ellis van Liempt       oncology-trialssecretariat@umcutrecht.nl   
Principal Investigator: Eelke Gort, MD         
Sponsors and Collaborators
Genmab
Seattle Genetics, Inc.
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Belgian Gynaecological Oncology Group
Gynecologic Oncology Group
Merck Sharp & Dohme Corp.

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Responsible Party: Genmab
ClinicalTrials.gov Identifier: NCT03786081     History of Changes
Other Study ID Numbers: GCT1015-05
InnovaTV 205 ( Other Identifier: Genmab )
MK3475 KN 834 ( Other Identifier: Merck )
First Posted: December 24, 2018    Key Record Dates
Last Update Posted: August 14, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Genmab:
cervical carcinoma
Additional relevant MeSH terms:
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Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Bevacizumab
Pembrolizumab
Carboplatin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors