NCT04697628CompletedPhase 3
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
Seagen, a wholly owned subsidiary of Pfizer398 sites in 4 countries502 target enrollmentStarted: February 22, 2021Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 502
- Locations
- 398
- Primary Endpoint
- Overall Survival
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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
- •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.
Arms & Interventions
Tisotumab vedotin
Experimental
Tisotumab vedotin monotherapy
Intervention: tisotumab vedotin (Drug)
Chemotherapy
Active Comparator
Investigator's choice of one chemotherapy treatment (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed)
Intervention: vinorelbine (Drug)
Chemotherapy
Active Comparator
Investigator's choice of one chemotherapy treatment (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed)
Intervention: gemcitabine (Drug)
Chemotherapy
Active Comparator
Investigator's choice of one chemotherapy treatment (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed)
Intervention: pemetrexed (Drug)
Chemotherapy
Active Comparator
Investigator's choice of one chemotherapy treatment (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed)
Intervention: irinotecan (Drug)
Chemotherapy
Active Comparator
Investigator's choice of one chemotherapy treatment (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed)
Intervention: topotecan (Drug)
Outcomes
Primary Outcomes
Overall Survival
Time Frame: From randomization to date of death due to any cause or censoring date, whichever occurred first (maximum up to 25 months)
Overall survival is defined as the time from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive.
Secondary Outcomes
- Progression Free Survival (PFS) as Assessed by Investigator(From the date of randomization to first documentation of PD or death due to any cause, or censoring date whichever occurred first (maximum up to 25 months))
- EQ-5D Visual Analog Scale (VAS) Scores(From start of treatment until end of follow-up)
- Confirmed Objective Response Rate (ORR) as Assessed by Investigator(From the date of randomization until date of confirmed CR or PR (maximum up to 25 months))
- Duration of Response (DOR) by Investigator Assessment(From the date of first documented response of CR or PR to the first documented PD or death from any cause, whichever occurred first (maximum up to 25 months))
- EuroQOL Five Dimensions Five Level (EQ-5D-5L) Index Score(From start of treatment until end of follow-up)
- European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Total Score(From start of treatment until end of follow-up)
- EORTC Quality of Life Questionnaire Cervical Cancer Module (QLQ-CX24) Total Scores(From start of treatment until end of follow-up)
- Time-to-Response (TTR) as Assessed by the Investigator(From the date of randomization to date of date of the first confirmed objective response (maximum up to 25 months))
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From start of treatment up to 30 days after last dose of study treatment (up to 25 months))
Investigators
Study Sites (398)
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