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Metastatic Cervical CancerPhase 2ITTACCNCT05614453

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

A Phase 2 study testing Tislelizumab and Sitravatinib in people with Metastatic Cervical Cancer, run by Australia New Zealand Gynaecological Oncology Group.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Cervical Cancer
What is being tested?
Tislelizumab and Sitravatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Jun 2023to 28 Jun 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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
  • Received prior bevacizumab-containing therapy, which was discontinued due to toxicity
  • Was deemed unsuitable for prior bevacizumab therapy for one of the following reasons: (i) unacceptable risk of fistula formation, (ii) poorly controlled hypertension, (iii) "low risk" disease according to the Moore Criteria
  • Refused prior bevacizumab therapy
  • Patients must meet at least one of the following criteria regarding prior paclitaxel therapy:
  • Received prior paclitaxel-containing therapy, which was discontinued due to progression of disease
  • Received prior paclitaxel-containing therapy, which was discontinued due to toxicity
  • Was deemed unsuitable for prior paclitaxel therapy for one of the following reasons:
  • Significant neuropathy
  • Allergy to paclitaxel or its components
  • Refused prior paclitaxel therapy
  • 1 prior line of combination which include an anti-PD-1/ anti-PD-L1 inhibitor
  • Previous progression after cisplatin or carboplatin-based combinations
  • Anticipated life expectancy > 12 weeks
  • Willing and able to comply with clinic visits and study-related procedures
  • Availability of archival tumour sample from either the primary or metastatic tumour. If no archival tumour is available, a fresh tissue biopsy to be performed if feasible and safe to do so. Where tumour tissue is not available, this will not preclude trial participation

Who cannot join

  • Ongoing or recent (within 5 years prior to registration) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest higher risk for severe irAEs. The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism that required only hormone replacement, or psoriasis that does not require systemic treatment
  • 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:
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  • 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:
  • Patients with bleeding or thrombotic disorders or who use anticoagulants such as warfarin or similar agents requiring therapeutic INR monitoring
  • Patients with signs or history of significant bleeding, within 4 weeks prior to registration, patients with any bleeding events ≥ CTCAE Grade 3, unhealed wounds, ulcers, or fractures
  • Patients with arterial thrombotic event that occurred within 6 months prior to
  • registration, such as cerebrovascular accident (including temporary ischemic attack)
  • Venous thrombotic events such as deep vein thrombosis and pulmonary embolism that causes haemodynamic compromise or venous thrombotic events within 4 weeks of diagnosis (treated asymptomatic patients > 4 weeks after diagnosis permitted at Investigators' discretion)
  • Immunosuppressive corticosteroid doses (> 10mg prednisone daily or equivalent) within 4 weeks prior to registration
  • Active bacterial, viral, fungal or mycobacterial infection requiring therapy, including known infection with HIV, or active infection with HBV or HCV
  • History of pneumonitis within the last 5 years
  • Any anticancer treatment (chemotherapy, targeted systemic therapy, photodynamic therapy), investigational, or standard of care, within 30 days prior to registration or planned to occur during the study period (patients receiving bisphosphonates or denosumab are not excluded)
  • History of documented allergic reactions or acute hypersensitivity reactions attributed to antibody treatments
  • Concurrent malignancy other than cervical cancer and/or history of malignancy other than cervical cancer within 3 years prior to registration, except for tumours with negligible risk of metastasis or death, such as adequately treated cutaneous squamous cell carcinoma or basal cell carcinoma of the skin or ductal carcinoma in situ of the breast. Patients with hematologic malignancies (e.g., CLL) are excluded
  • Any acute or chronic psychiatric problems that, in the opinion of the Investigator, make the patient ineligible for participation
  • Patients with a history of solid organ transplant (patients with prior corneal transplant(s) may be allowed to enrol after discussion with and approval from the CPI)
  • Any medical co-morbidity, physical examination finding, or metabolic dysfunction, or clinical laboratory abnormality that, in the opinion of the Investigator, renders the patient unsuitable for participation due to excessive safety risks and/or potential to affect interpretation of results of the study
  • Pregnant or breastfeeding persons
  • People of Childbearing Potential who are unwilling to practice highly effective contraception prior to the initial study drug treatment, during the study, and for at least 6 months after the last dose.
  • Prior treatment with idelalisib
  • Prior treatment with live vaccines within 30 days prior to registration. Patients must not be treated with live vaccines during the study and up to 5 half-lives following the last dose of study drug
  • Patients with prior treatment on any clinical trial within 30 days prior to registration. Non-interventional and observational trials are acceptable

About this study

Official title: A Phase II Trial of Tislelizumab in Combination With Sitravatinib for Recurrent/Metastatic Cervical Cancer After Platinum-Based Chemotherapy

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.

Read the detailed description

Monoclonal antibodies that target either PD-1, PD-L1, or the other checkpoint inhibitors can block binding and boost the immune response against cancer cells. However, many early-phase studies with single immune checkpoint inhibitors did not show enough power to achieve a promising clinical response, and several trials are evaluating different strategies to overcome immune tolerance via combination therapies. Combining an immunotherapeutic PD-1 checkpoint inhibitor with an agent that has both immune modulatory and antitumor properties could enhance the antitumor efficacy observed with either agent alone.

Sitravatinib is a spectrum selective RTK inhibitor that inhibits several closely related RTKs, including the TAM family (Tyro3/Axl/MER), VEGFR2, KIT, and MET. Tislelizumab is a humanised IgG4-variant monoclonal antibody against PD-1. In addition to the antiangiogenesis activity of sitravatinib, sitravatinib in combination with tislelizumab may elicit greater anti-tumour activity, as sitravatinib is predicted to enhance several steps in the cancer immunity cycle that may augment the efficacy of tislelizumab.

In summary, sitravatinib inhibits key molecular and cellular pathways strongly implicated in carcinogenesis and drug resistance and represents a reasonable strategy to enhance anti-tumour immunity when combined with tislelizumab.

The ITTACc study aims to assess the overall response rate of the combination of tislelizumab with sitravatinib along with other key outcomes detailed below.

Being tested
Tislelizumab, Sitravatinib
Medical subject headings
Uterine Cervical Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TislelizumabDrug

    Also called BGB-A317

    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.

  • SitravatinibDrug

    Also called MGCD516

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

Study groups in NCT05614453
Study groupRoleWhat they receive
TreatmentExperimentalTislelizumab 200mg (IV) every 21 days for up to 35 cycles Sitravatinib 100mg (oral) given daily until disease progression or unacceptable toxicity
Receives: Drug: Tislelizumab; Drug: Sitravatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR)

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

    Measured: Up to 2 years

Secondary outcomes (3)

  1. Overall Survival (OS)

    To estimate OS at 12 months. Defined as the time from the start of treatment until death of any cause.

    Measured: 12 months

  2. Progression Free Survival (PFS)

    To determine PFS, defined as the time from start of treatment until first evidence of disease progression as per RECIST 1.1 or death from any cause.

    Measured: Up to 4 years

  3. Adverse events

    Determine toxicity, frequency, and severity of Adverse Events (CTCAE V5.0)

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Nov 2022
  2. Study startJun 2023 (estimated)
  3. Primary completionJun 2023 (estimated)
  4. Study completion28 Jun 2023

Why it stopped: BeiGene has withdrawn their support owing to sitravatinib supply concerns. Mirati is ceasing further development of sitravatinib owing to the negative results of the SAPPHIRE trial which used sitravatinib in 2nd line met NSCLC setting.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Phase II, open-label, multi-centre study, based on Simon's two-stage design
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05614453
Sponsor's protocol ID
ANZGOG 2002/2021
Acronym
ITTACC
Status last verified
Jun 2023
First submitted
3 Nov 2022
Last updated
29 Jun 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tislelizumab and Sitravatinib in people with Metastatic Cervical Cancer, run by Australia New Zealand Gynaecological Oncology Group.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 29 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05614453.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2023.

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