Efficacy and safety of tisotumab vedotin (HuMax®-TF-ADC) in combination in recurrent or Stage IVB cervical cancer
- Conditions
- recurrent or stage IVB 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
- EUCTR2017-004758-40-CZ
- Lead Sponsor
- Genmab A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 140
- 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 only).
- Must have baseline measurable disease per RECIST v1.1 (all arms).
- 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. A WOCBP must agree to use adequate contraception during and for 6 months after the last dose of trial treatment administration (all arms).
- 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).
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 95
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45
- 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 (All arms)
- 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 (All arms)
- Requires anti-coagulation therapy (Arm A only).
- Known history of thromboembolic events (Arm A only).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Dose escalation: To establish the MTD and RP2D of tisotumab vedotin in combination in subjects with cervical cancer<br>Dose expansion: Evaluate the antitumor activity of tisotumab vedotin in combination in subjects with cervical cancer;Secondary Objective: • Assess safety and tolerability of tisotumab vedotin in combination. <br>• Evaluate anti tumor activity<br>• Evaluate durability of response of tisotumab vedotin in combination.<br>• Evaluate clinical efficacy with tisotumab vedotin in combination.<br>• To evaluate the pharmacokinetics (PK) and immunogenicity of tisotumab vedotin alone or in combination.<br>;Primary end point(s): Dose escalation: Incidences of DLTs, AEs, SAEs, infusion-related AEs, CTCAE grade = 3 AEs, and AEs related to trial treatment during the trial<br>Dose expansion: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1;Timepoint(s) of evaluation of this end point: • During the trial, see protocol
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Adverse events (AEs) and evaluation of safety laboratory parameters.<br>• Objective Response Rate (ORR) per RECIST v1.1 (only dose escalation)<br>• Duration of Response (DOR) per RECIST v1.1. <br>• Time to Response (TTR) per RECIST v1.1.<br>• Progression free survival (PFS) per RECIST v1.1.<br>• Overall Survival (OS)<br>• PK-concentrations and anti-drug antibodies (ADA) associated with tisotumab vedotin in combination.<br>;Timepoint(s) of evaluation of this end point: • During the trial, see protocol