E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
recurrent or stage IVB cervical cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008342 |
E.1.2 | Term | Cervix carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Dose escalation: To establish the MTD and RP2D of tisotumab vedotin in combination in subjects with cervical cancer
Dose expansion: Evaluate the antitumor activity of tisotumab vedotin in combination in subjects with cervical cancer |
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E.2.2 | Secondary objectives of the trial |
• Assess safety and tolerability of tisotumab vedotin in combination.
• Evaluate anti tumor activity
• Evaluate durability of response of tisotumab vedotin in combination.
• Evaluate clinical efficacy with tisotumab vedotin in combination.
• To evaluate the pharmacokinetics (PK) and immunogenicity of tisotumab vedotin alone or in combination.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 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). |
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E.4 | Principal 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 (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).
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E.5 End points |
E.5.1 | 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
Dose expansion: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• During the trial, see protocol |
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E.5.2 | Secondary end point(s) |
• Adverse events (AEs) and evaluation of safety laboratory parameters.
• Objective Response Rate (ORR) per RECIST v1.1 (only dose escalation)
• Duration of Response (DOR) per RECIST v1.1.
• Time to Response (TTR) per RECIST v1.1.
• Progression free survival (PFS) per RECIST v1.1.
• Overall Survival (OS)
• PK-concentrations and anti-drug antibodies (ADA) associated with tisotumab vedotin in combination.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• During the trial, see protocol |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Phase 1b (dose escalation - dose expansion) |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 6 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Czech Republic |
Denmark |
Germany |
Ireland |
Italy |
Netherlands |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial is considered completed four years after the last subject is enrolled |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |