A RANDOMIZED, OPEN-LABEL TRIAL TO COMPARE TISOTUMAB VEDOTIN TO INVESTIGATOR'S CHOICE CHEMOTHERAPY IN PATIENTS WITH CERVICAL CANCER
- Conditions
- Second- or Third-Line Recurrent or Metastatic Cervical CancerMedDRA version: 21.1Level: PTClassification code 10008342Term: Cervix carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001655-39-ES
- Lead Sponsor
- Genmab A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 482
1.Age =18 years (for subjects in Japan, age =20 years).
2.Must sign an informed consent form (ICF) indicating that they understand the purpose of and procedures required for the trial and are willing to participate in the trial prior to any other trial-related assessments or procedures.
3.Has recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology, and:
a.Has experienced disease progression during or after treatment with standard of care systemic therapy defined as either:
- paclitaxel+cisplatin+bevacizumab, or
- paclitaxel+carboplatin+bevacizumab, or
- paclitaxel+topotecan/nogitecan+bevacizumab
b.Has received 1 or 2 prior systemic therapy regimens for recurrent and/or metastatic cervical cancer.
c.Is not a candidate for curative therapy, including but not limited to radiotherapy or exenterative surgery.
5.Acceptable renal function
6.Acceptable liver function
7.Acceptable hematological status
8.Has ECOG PS of 0 or 1 prior to randomization.
10.Has a negative serum pregnancy test for female subjects of reproductive potential. Subjects that are postmenopausal or permanently sterilized (refer to Section 10.1.4) can be considered as not having reproductive potential.
11.Subjects of reproductive potential must agree to use adequate contraception during and for 6 months after the last trial treatment administration.
13.Where required by local health authorities, has negative serology for hepatitis B surface antigen (HBsAg)/HBV DNA, or hepatitis C antibody (HCVAb) or RNA. Active hepatitis C is defined by a known positive HCVAb result and known quantitative HCV RNA results greater than the lower limits of detection of the assay.
14.Must provide a fresh or archival biopsy prior to the first planned administration of trial treatment, unless determined it is unfeasible after sponsor medical review.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 386
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 96
1.Has primary neuroendocrine, lymphoid, sarcomatoid, or other histologies not mentioned in inclusion criterion 3
2.Has clinically significant bleeding issues or risks
3. Clinically significant cardiac disease
5.Ocular surface disease Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or above, any prior episode of cicatricial conjunctivitis, or any prior episode of Stevens-Johnson syndrome.
6.Other cancer: known past or current malignancy other than inclusion diagnosis, except for: non-invasive basal cell or squamous cell skin carcinoma; non-invasive, superficial bladder cancer; any curable cancer with a complete response (CR) of =5 years duration.
8.Surgery/procedures: major surgery within 4 weeks or minor surgery within 7 days prior to the first trial treatment administration. Subjects must have recovered adequately from the toxicity or complications from the intervention prior to starting trial treatment. Subjects who have planned major surgery during the treatment period must be excluded from the trial.
9.Peripheral neuropathy =grade 2.
10.Prior anti-cancer therapy:
a.Any prior treatment with MMAE-derived drugs.
b.Radiotherapy within 21 days prior to the first administration of trial treatment. Subjects must have recovered from all clinically significant radiation-related toxicities. At least 42 days must have elapsed from the last administration of chemo radiotherapy.
c.Is currently participating in or has participated in a trial of an investigational agent or device and received active treatment within 28 days prior to the first dose of trial treatment.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: •To demonstrate improvement in clinical efficacy of tisotumab vedotin compared to chemotherapy in subjects with second- or third-line (2L-3L) cervical cancer;Secondary Objective: •To further demonstrate improvement in clinical efficacy of tisotumab vedotin compared to chemotherapy in subjects with 2L-3L cervical cancer<br>•To demonstrate improvement in antitumor activity of tisotumab vedotin compared to chemotherapy in subjects with 2L-3L cervical cancer<br>•To evaluate the safety and tolerability of tisotumab vedotin<br>•To assess health-related quality of life (HRQOL);Primary end point(s): •Overall survival (OS);Timepoint(s) of evaluation of this end point: During the trial, see protocol
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •Progression-free survival (PFS) based on Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 as assessed by the investigator <br>•Confirmed overall response rate (ORR) based on RECIST v1.1 as assessed by the investigator<br>•Incidence of adverse events (AEs)<br>•EQ-5D-3L index<br>•EQ-5D visual analog scale (VAS)<br>•EORTC-QLQ-C30<br>•EORTC-QLQ-CX24;Timepoint(s) of evaluation of this end point: During the trial, see protocol