Clinical Trials /

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

NCT03786081

Description:

This is an open label, multi-center trial of tisotumab vedotin monotherapy and 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.

Related Conditions:
  • Cervical Adenocarcinoma
  • Cervical Adenosquamous Carcinoma
  • Cervical Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy of Tisotumab Vedotin Monotherapy & in Combination With Other Cancer Agents in Subjects With Cervical Cancer
  • Official Title: A Phase 1b/2 Open-Label Trial of Tisotumab Vedotin (HuMax®-TF-ADC) Monotherapy and in Combination With Other Agents in Subjects With Recurrent or Stage IVB Cervical Cancer

Clinical Trial IDs

  • ORG STUDY ID: GCT1015-05
  • SECONDARY ID: InnovaTV 205
  • SECONDARY ID: MK3475 KN 834
  • NCT ID: NCT03786081

Conditions

  • Cervical Cancer

Interventions

DrugSynonymsArms
Tisotumab VedotinA: Tisotumab Vedotin + bevacizumab
BevacizumabAvastinA: Tisotumab Vedotin + bevacizumab
PembrolizumabKeytrudaB: Tisotumab vedotin + pembrolizumab
CarboplatinParaplatinC: Tisotumab vedotin + carboplatin

Purpose

This is an open label, multi-center trial of tisotumab vedotin monotherapy and 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.

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 and Arm G treated with
      tisotumab vedotin alone. Subjects enrolled to Arms D, E, and F will receive the RP2D of
      tisotumab vedotin established in the dose escalation part. Subjects enrolled to Arm G will
      receive tisotumab vedotin weekly for three weeks and 1 week off (28 day treatment cycle).
    

Trial Arms

NameTypeDescriptionInterventions
A: Tisotumab Vedotin + bevacizumabExperimentalDose escalation: Tisotumab vedotin in combination with bevacizumab once every three weeks in previously treated patients
  • Tisotumab Vedotin
  • Bevacizumab
B: Tisotumab vedotin + pembrolizumabExperimentalDose escalation: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients
  • Tisotumab Vedotin
  • Pembrolizumab
C: Tisotumab vedotin + carboplatinExperimentalDose escalation: Tisotumab vedotin in combination with carboplatin once every three weeks in previously treated patients
  • Tisotumab Vedotin
  • Carboplatin
D: Tisotumab vedotin + carboplatinExperimentalDose expansion:Tisotumab vedotin in combination with carboplatin once every three weeks in previously untreated patients
  • Tisotumab Vedotin
  • Carboplatin
E: Tisotumab vedotin + pembrolizumabExperimentalDose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously untreated patients
  • Tisotumab Vedotin
  • Pembrolizumab
F: Tisotumab vedotin + pembrolizumabExperimentalDose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients
  • Tisotumab Vedotin
  • Pembrolizumab
G: Tisotumab vedotin monotherapyExperimentalDose expansion: Tisotumab vedotin monotherapy weekly for three weeks and 1 week off (28 day treatment cycle) in previously treated patients.
  • Tisotumab Vedotin

Eligibility 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 prior systemic therapies for recurrent or
             stage IVB cervical cancer (Arm F and G 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose escalation: Dose Limiting Toxicities (DLTs)
Time Frame:DLTs will be identified during the first treatment cycles (21 days cycles)
Safety Issue:
Description:To establish the MTD and RP2D of tisotumab vedotin in combination

Secondary Outcome Measures

Measure:Adverse events (AEs)
Time Frame:up to 2 years
Safety Issue:
Description:Frequency, duration, and severity of adverse events (AEs)
Measure:Objective Response Rate
Time Frame:approximately 2 years
Safety Issue:
Description:Objective Response Rate (ORR) based upon RECIST v1.1.
Measure:Duration of Response
Time Frame:approximately 2 years
Safety Issue:
Description:Duration of Response (DOR) based upon RECIST v1.1.
Measure:Time to Response
Time Frame:approximately 2 years
Safety Issue:
Description:Time to Response (TTR) based upon RECIST v1.1.
Measure:Progression free survival
Time Frame:approximately 2 years
Safety Issue:
Description:Progression free survival (PFS) based upon RECIST v1.1.
Measure:Overall Survival
Time Frame:approximately 2 years
Safety Issue:
Description:Overall Survival (OS)

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Genmab

Trial Keywords

  • cervical carcinoma

Last Updated

December 19, 2019