Recurrent Cervical Cancer
Conditions
Interventions
None listed
Sponsors
Seagen
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1.Age >=18 years , or considered an adult by local regulations, at time of consent. 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, or + anti-PD-(L)1 agent paclitaxel+carboplatin+bevacizumab, or + anti-PD-(L)1 agent paclitaxel+topotecan/nogitecan+bevacizumab + anti-PD-(L)1 agent 2. Has ECOG performance status of 0 or 1 prior to randomization. 3. Has life expectancy of at least 3 months. 4. Has a negative serum pregnancy test for participants of reproductive potential. Participants that are postmenopausal, permanently sterilized or previously subjected to bilateral oophorectomy, bilateral salpingectomy and/or hysterectomy can be considered as not having reproductive potential (refer to Section 10.4 of protocol). 5. Participants of reproductive potential must agree to use adequate contraception during and for 6 months after the last study treatment administration. Adequate contraception is defined as highly effective methods of contraception (refer to Section 10.4 of protocol). Two highly effective methods of contraception must be used in countries where this is required. 6. Must agree not to breastfeed or donate ova, starting at the time of informed consent and continuing through 6 months after receiving the last dose of study drug administration 7. 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. 8. Must be able to provide tumor tissue. The most recent archival tumor biopsy is preferred if collected within the last 2 years. If an archival tumor biopsy less than 2 years old is not available, a fresh tumor biopsy will be collected before initiation of study treatment, if clinically feasible. If a fresh biopsy cannot be collected, the most recent archival tumor sample may be submitted, even if obtained more than 2 years prior to participant enrollment. 9. Must be willing and able to adhere to the prohibitions and restrictions specified in this protocol. 10. Measurable disease according to RECIST v1.1 as assessed by the investigator 11. Must demonstrate acceptable screening laboratory values (please refer to protocol pg. 32)
Exclusion criteria
Exclusion criteria: 1. Has primary neuroendocrine, lymphoid, sarcomatoid, or other histologies not mentioned in inclusion criterion 3 (refer to Section 5.1 of protocol). 2. Has clinically significant bleeding issues or risks: - Known past or current coagulation defects leading to an increased risk of bleeding - Diffuse alveolar hemorrhage from vasculitis - Known bleeding diathesis - Ongoing major bleeding (i.e. participant requires a transfusion of >2 platelet concentrates within 14 days of the first dose of the study treatment) - Trauma with increased risk of life-threatening bleeding - History of severe head trauma or intracranial surgery within 8 weeks of study entry. 3. Has cardiovascular issues or risks: - Clinically significant cardiac disease, including unstable angina or acute myocardial infarction, 6 months prior to screening - Any medical history of congestive heart failure (grade III or IV as classified by the New York Heart Association) - Any medical history of decreased ejection fraction of 450 msec) - A complete left bundle branch block (defined as QRS interval >=120 msec in left bundle branch block form) or an incomplete left bundle branch block 4. Central nervous system (CNS): any history of intracerebral arteriovenous malformation, cerebral aneurysm, or stroke (transient ischemic attack >1 month prior to screening is allowed). 5. Ophthalmological conditions: 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 are ineligible. Cataracts alone is not an exclusion criterion. 6. Other cancer: known past or current malignancy other than inclusion diagnosis. Exceptions are malignancies with a negligible risk of metastasis or death (e.g., 5year OS =90%) such as non-invasive basal cell or squamous cell skin carcinoma; non-invasive, superficial bladder cancer, and ductal carcinoma in situ. 7. Brain metastases are allowed if the following criteria are met: definitive therapy (eg, surgery or stereotactic brain radiotherapy) has been completed >8 weeks before the first dose of study treatment; no evidence of clinical or radiologic progression of the brain metastases; participant has completed perioperative corticosteroid therapy or steroid taper. NOTE: Chronic steroid therapy is acceptable provided that the dose is stable for 1 month prior to screening. 8. Surgery/Procedures: major surgery within 4 weeks or minor surgery within 7 days prior to the first study treatment administration. 9. Peripheral neuropathy grade > 2 10. Prior anti-cancer therapy: - Any prior treatment with MMAE-derived drug. - Radiotherapy within 21 days prior to the first administration of study treatment. Participants must have recovered from all clinically significant radiation-related toxicities. At least 42 days must have elapsed from the last administration of chemo radiotherapy. - Small molecules, chemotherapy, immunotherapy, or m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Demonstrate improvement in clinical efficacy of tisotumab vedotin compared to chemotherapy in participants with second- or third-line (2L-3L) cervical cancer (Overall Survival-OS) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Assess improvement in clinical efficacy of tisotumab vedotin compared to chemotherapy (Progression-free survival-PFS) 2. Demonstrate improvement in antitumor activity of tisotumab vedotin compared to chemotherapy (Objective Response Rate - ORR) 3. Assess the antitumor response of tisotumab vedotin and chemotherapy (Time-to-response - TTR) and (Duration of response - DOR) 4. Evaluate the safety and tolerability of tisotumab vedotin 5. Assess health-related quality of life (HRQOL) | — |
Countries
Netherlands
Outcome results
None listed