A Randomized, Open-Label Trial to Compare Tisotumab Vedotin to Investigator's Choice Chemotherapy in Patients with Cervical Cancer

Phase 1

• Conditions: Second- or Third-Line Recurrent or Metastatic Cervical Cancer; MedDRA 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: EUCTR2019-001655-39-FI
• Lead Sponsor: Seagen Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-04-27
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 482

Inclusion Criteria

1.Age =18 years, or considered an adult by local regulations, at time of consent.
2.Must sign an informed consent form (ICF) indicating that they understand the purpose of and procedures required for the trial and are willing to participate in the trial prior to any other trial-related assessments or procedures.
3.Has recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology, and:
a.Has experienced disease progression during or after treatment with standard of care systemic therapy defined as either:
- paclitaxel+cisplatin+bevacizumab, or + anti-PD-(L) 1 agent, or
- paclitaxel+carboplatin+bevacizumab, or + anti-PD-(L) 1 agent, or
- paclitaxel+topotecan/nogitecan+bevacizumab + anti-PD-(L) 1 agent
b.Has received 1 or 2 prior systemic therapy regimens for recurrent and/or metastatic cervical cancer.
c.Is not a candidate for curative therapy, including but not limited to radiotherapy or exenterative surgery.
4. Measurable disease according to RECIST v1.1 as assessed by the investigator
5.Acceptable screening laboratory values including renal function, liver function and hematological status.
6.Has ECOG PS of 0 or 1 prior to randomization.
7. Has life expectancy of at least 3 months.
8.Has a negative serum pregnancy test for female subjects of reproductive potential. Subjects that are postmenopausal or permanently sterilized can be considered as not having reproductive potential.
9.Subjects of reproductive potential must agree to use adequate contraception during and for 6 months after the last trial treatment administration.
10. 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.
11.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.
12. Must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
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 386
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 96

Exclusion Criteria

1. Primary neuroendocrine, lymphoid, sarcomatoid, or other histologies not mentioned in inclusion criterion 3
2. Clinically significant bleeding issues or risks
3. Clinically significant cardiac disease
4. History of intracerebral arteriovenous malformation, cerebral aneurysm, or stroke
5. Ocular surface disease Common Terminology Criteria for Adverse
Events (CTCAE) grade 2 or above, any prior episode of cicatricial
conjunctivitis, or any prior episode of Stevens-Johnson syndrome.
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, any 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.
8.Surgery/procedures: major surgery within 4 weeks or minor surgery within 7 days prior to the first trial treatment administration. Subjects must have recovered adequately from the toxicity or complications from the intervention prior to starting trial treatment. Subjects who have planned major surgery during the treatment period must be excluded from the trial.
9.Peripheral neuropathy =grade 2.
10.Prior anti-cancer therapy:
a.Any prior treatment with MMAE-derived drugs.
b.Radiotherapy within 21 days prior to the first administration of trial
treatment. Subjects must have recovered from all clinically significant
radiation-related toxicities. At least 42 days must have elapsed from the last administration of chemo radiotherapy.
c. Is currently participating in or has participated in a trial of an
investigational agent or device and received active treatment within 28days prior to the first dose of trial treatment.
11. Other:
a. Ongoing significant, uncontrolled medical condition.
b. Clinically significant active viral, bacterial, or fungal infection requiring IV or oral treatment with antimicrobial therapy ending <7 days prior to first study treatment administration.
c. Clinically relevant bilateral hydronephrosis which cannot be alleviated by ureteral stents or percutaneous drainage.
d. Participants with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration or nutrition at the time of the first dose of study treatment.
12. Has known seropositivity of human immunodeficiency virus (HIV); known medical history of hepatitis B or C infection. Note: No testing for HIV, hepatitis B, or hepatitis C is required, unless mandated by local health authorities. Exceptions include latent or controlled HIV infection.
13. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (dose exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of tisotumab vedotin.
14. Is pregnant or intends to conceive children within 6 months of ending study treatment.
15. Is breast feeding and cannot discontinue breast feeding for the duration of the study and =6 months after the last study treatment administration.
16. Any condition for which, in the opinion of the investigator, participati

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified