Tislelizumab in Combination With Sitravatinib for Recurrent/Metastatic Cervical Cancer After Platinum-Based Chemotherapy

NCT05614453 | Withdrawn Phase 2

• 1 other identifier: ANZGOG 2002/2021
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to learn about the effect of the combination treatment of sitravatinib with tislelizumab in patients with Recurrent/Metastatic Cervical Cancer after Platinum-Based Chemotherapy. The main question it aims to answer is the percentage of people in the study who have a partial or complete response to the treatment. Participants will receive treatment under the care of their treating physician and will be reviewed regularly.

Conditions

Metastatic Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  To assess the ORR of the combination of tislelizumab with sitravatinib using RECIST 1.1

  Up to 2 years

Secondary Outcomes (3)

• Overall Survival (OS)

  12 months

• Progression Free Survival (PFS)

  Up to 4 years

• Adverse events

  Up to 4 years

Other Outcomes (2)

• Patient reported Quality Of Life (QOL) as measured by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for cancer patients (QLQ-C30)

  Up to 4 years

• Patient reported Quality Of Life (QOL) as measured by EORTC Quality of Life questionnaire for cervical cancer patients (QLQ-CX24)

  Up to 4 years

Study Arms (1)

Treatment

EXPERIMENTAL

Tislelizumab 200mg (IV) every 21 days for up to 35 cycles Sitravatinib 100mg (oral) given daily until disease progression or unacceptable toxicity

Drug: Tislelizumab; Drug: Sitravatinib

Interventions

Tislelizumab DRUG

Tislelizumab is an investigational, humanised-IgG4 monoclonal antibody with high affinity/binding specificity for PD-1. It is engineered to minimise binding to FcγR on macrophages to abrogate antibody-dependent cellular phagocytosis.

Also known as: BGB-A317

Treatment

Sitravatinib DRUG

Sitravatinib is an orally bioavailable receptor tyrosine kinase (RTK) inhibitor with potential anti-neoplastic activity.

Also known as: MGCD516

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has provided written informed consent
• Patient must be ≥ 18 years of age at screening
• Recurrent, persistent, and/or metastatic cervical cancer with squamous cell histology, adeno-squamous carcinoma, and adenocarcinoma for which there is not a curative-intent option (surgery or radiation therapy with or without chemotherapy)
• Measurable disease, as defined by RECIST 1.1
• ECOG performance status ≤ 2
• Adequate bone marrow, hepatic and renal function documented within 10 days prior to registration, defined as:
• Haemoglobin ≥ 90g/L
• ANC ≥ 1.5 x 109/L
• Platelets ≥ 75 x 109/L
• Total bilirubin ≤ 1.5x ULN if liver metastases ≤ 3x ULN. Patients with Gilbert's syndrome, and total bilirubin up to 3x ULN may be eligible after communication with and approval from the CPI
• AST and ALT ≤ 3x ULN (or ≤ 5.0x ULN, if liver metastases)
• ALP ≤ 2.5x ULN (or ≤ 5.0x ULN, if liver or bone metastases)
• Serum creatinine ≤ 1.5x ULN or estimated creatinine clearance \> 45mL/min using the Cockcroft-Gault equation
• Patients must meet at least one of the following criteria regarding prior bevacizumab therapy:
• Received prior bevacizumab-containing therapy, which was discontinued due to progression of disease

You may not qualify if:

• Prior treatment with other systemic immune-modulating agents that was (a) within fewer than 28 days prior to registration, or (b) associated with irAEs of any grade within 90 days prior to registration, or (c) associated with toxicity that resulted in discontinuation of the immune-modulating agent.
• Known history of brain metastasis(es) that may be considered active (screening imaging of brain is not required unless there is clinical suspicion of brain metastases). Patients with previously treated brain metastases may participate provided that the lesions are stable (without evidence of progression for at least 6 weeks on imaging obtained during the screening period), there is no evidence of new or enlarging brain metastases, and the patient does not require any immunosuppressive doses of systemic corticosteroids for management of brain metastases within 4 weeks prior to registration
• Variant histology's such as high-grade neuroendocrine carcinoma, small cell carcinoma, mucinous carcinoma, sarcomatous tumours or mixed histology's containing these components
• Patients with tumour shown by imaging to be located around important vascular structures or if the Investigator determines that the tumour is likely to invade important blood vessels and may cause fatal bleeding (i.e., radiological evidence of tumours invading or abutting major blood vessels)
• Any of the following cardiovascular risk factors:
• Cardiac chest pain, defined as moderate pain that limits instrumental ADL, ≤ 28 days prior to registration
• Symptomatic pulmonary embolism ≤ 28 days prior to registration
• Any history of acute myocardial infarction ≤ 6 months prior to registration
• Any history of heart failure meeting NYHA Classification III or IV ≤ 6 months prior registration
• Any ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months prior to registration
• QTc ≥ 470msec in females and ≥ 450msec in males (based on average of screening triplicates)
• Cardiac LVEF ≤ 50% or lower limit of normal as assessed by echocardiography or MUGA
• Patients with inadequately controlled hypertension (defined as systolic blood pressure \> 150mmHg and/or diastolic blood pressure \> 100mmHg, that is persistent)
• Any history of cerebrovascular accident ≤ 6 months prior to registration
• Significant bleeding and thrombotic risks:

Sponsors & Collaborators

• Australia New Zealand Gynaecological Oncology Group: lead
• BeiGene: collaborator

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

tislelizumab; sitravatinib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Jeff Goh, MBBS, FRACP

  Royal Brisbane & Womens Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase II, open-label, multi-centre study, based on Simon's two-stage design

Study Record Dates

• First Submitted: November 3, 2022
• First Posted: November 14, 2022
• Study Start: June 1, 2023
• Primary Completion: June 1, 2023
• Study Completion: June 28, 2023
• Last Updated: June 29, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share