Tisotumab Vedotin vs Chemotherapy in Recurrent or Metastatic Cervical Cancer

Study Overview
=================
Brief Summary
-----------------
This trial is being done to find out whether tisotumab vedotin works better than chemotherapy to treat cervical cancer. People in this study have cervical cancer that has spread to other parts of the body (metastatic) or has come back after being treated (recurrent). Participants in this trial will be randomly assigned to one of two groups. One group will be treated with tisotumab vedotin. Participants in the other group will get one of five different chemotherapy drugs (topotecan, vinorelbine, gemcitabine, pemetrexed, or irinotecan). Participants and their doctors will know which group they are in. Participants in the chemotherapy group will decide with their study doctor which drug they will take.

Official Title
-----------------
A Randomized, Open-Label, Phase 3 Trial of Tisotumab Vedotin vs Investigator's Choice Chemotherapy in Second- or Third-Line Recurrent or Metastatic Cervical Cancer

Conditions
-----------------
Cervical Cancer

Intervention / Treatment
-----------------
* Drug: tisotumab vedotin
* Drug: topotecan
* Drug: vinorelbine
* Drug: gemcitabine
* Drug: irinotecan
* Drug: pemetrexed


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Has recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology, and: Has experienced disease progression during or after treatment with a standard of care systemic chemotherapy doublet, or platinum-based therapy (if eligible), defined as either: paclitaxel + cisplatin + bevacizumab + anti-PD-(L)1 agent, or paclitaxel + carboplatin + bevacizumab + anti-PD-(L)1 agent, or paclitaxel + topotecan/nogitecan + bevacizumab + anti-PD-(L)1 agent Note: In cases where bevacizumab and/or anti-PD-(L)1 agent is not a standard of care therapy or the participant was ineligible for such treatment according to local standards, prior treatment with bevacizumab and/or anti-PD-(L)1 agent is not required. Has received 1 or 2 prior systemic therapy regimens for recurrent and/or metastatic cervical cancer. Chemotherapy administered in the adjuvant or neoadjuvant setting, or in combination with radiation therapy, should not be counted as a systemic therapy regimen. Single agent therapy with an anti-PD(L)1 agent for r/mCC cancer should be counted. Measurable disease according to RECIST v1.1 as assessed by the investigator. Has ECOG performance status of 0 or 1 prior to randomization. Has life expectancy of at least 3 months. Exclusion Criteria Has primary neuroendocrine, lymphoid, sarcomatoid, or other histologies not mentioned as part of the inclusion criteria above. Has clinically significant bleeding issues or risks. This includes known past or current coagulation defects leading to an increased risk of bleeding; diffuse alveolar hemorrhage from vasculitis; known bleeding diathesis; ongoing major bleeding; trauma with increased risk of life-threatening bleeding or history of severe head trauma or intracranial surgery within 8 weeks of trial entry. Has any history of intracerebral arteriovenous malformation, cerebral aneurysm, or stroke (transient ischemic attack >1 month prior to screening is allowed). Active ocular surface disease or a history of cicatricial conjunctivitis or inflammatory conditions that predispose to cicatrizing conjunctivitis (e.g. Wagner syndrome, atopic keratoconjunctivitis, autoimmune disease affecting the eyes), ocular Stevens-Johnson syndrome or toxic epidermal necrolysis, mucus pemphigoid, and participants with penetrating ocular transplants. Cataracts alone is not an exclusion criterion. Major surgery within 4 weeks or minor surgery within 7 days prior to the first study treatment administration. Peripheral neuropathy ≥grade 2. Any prior treatment with monomethyl auristatin E (MMAE)-containing drugs. There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tisotumab vedotin<br>Tisotumab vedotin monotherapy | Drug: tisotumab vedotin<br>* 2.0 mg/kg every 3 weeks (Q3W)<br>* Other names: TIVDAK;|
| Active Comparator: Chemotherapy<br>Investigator's choice of one chemotherapy treatment (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) | Drug: topotecan<br>* 1 or 1.25 mg/m2 intravenous (IV) on Days 1 to 5, every 21 days<br>Drug: vinorelbine<br>* 30 mg/m2 IV on Days 1 and 8, every 21 days<br>Drug: gemcitabine<br>* 1000 mg/m2 IV on Days 1 and 8, every 21 days<br>Drug: irinotecan<br>* 100 or 125 mg/m2 IV weekly for 28 days, every 42 days<br>Drug: pemetrexed<br>* 500 mg/m2 IV on Day 1, every 21 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | OS is defined as the time from the date of randomization to the date of death due to any cause. | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the investigator | PFS per investigator is defined as the time from the date of randomization to the first documentation of disease progression per RECIST v.1.1 by the investigator, or to date of death due to any cause, whichever occurs earlier. | Up to approximately 1 year | 
| Confirmed objective response rate (ORR) based on RECIST v1.1 as assessed by the investigator | Confirmed objective response rate is defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) per RECIST v.1.1. | Up to approximately 6 months | 
| Time-to-response (TTR) as assessed by the investigator | TTR is defined as the time from the date of randomization to the date of first confirmed objective response (CR or PR that is subsequently confirmed). Only participants with confirmed CR or PR will be included in the analysis. | Up to approximately 6 months | 
| Duration of response (DOR) as assessed by the investigator | DOR is defined as the time from the date of first confirmed objective response (CR or PR that is subsequently confirmed) to the date of first documented PD per RECIST v1.1 or death from any cause, whichever occurs first. Only participants with confirmed CR or PR will be included in the analysis. | Up to approximately 1 year | 
| Incidence of adverse events (AEs) | Analyses of AEs will be summarized descriptively | Up to approximately 2 years | 
| Health-related quality of life as assessed by EQ-5D-5L index | EQ-5D-5L is a standardized instrument developed by the EuroQol Group as a measure of HRQOL that can be used in a wide range of health conditions and treatments. The EQ-5D-5L consists of a descriptive system and the EQ VAS. The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. | Up to approximately 2 years | 
| Health-related quality of life as assessed by EQ-5D visual analog scale (VAS) | EQ-5D-5L is a standardized instrument developed by the EuroQol Group as a measure of HRQOL that can be used in a wide range of health conditions and treatments. The EQ-5D-5L consists of a descriptive system and the EQ VAS. The EQ VAS records the participant's self-rated health on a vertical VAS. This can be used as a quantitative measure of health outcome that reflects the participant's own judgment. | Up to approximately 2 years | 
| Health-related quality of life as assessed by EORTC-QLQ-C30 | The QLQ-C30 is a validated questionnaire developed by the European Organization for Research and Treatment of Cancer (EORTC) to assess the quality of life of participants with cancer in multicultural clinical research settings. | Up to approximately 6 months | 
| Health-related quality of life as assessed by EORTC-QLQ-CX24 | The EORTC-QLQ-CX24 is a validated questionnaire developed by the EORTC to assess the quality of life in patients who are treated for cervical cancer both in clinical studies and in clinical practice. | Up to approximately 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Seattle Genetics