Cancer Molecular Screening and Therapeutics (MoST) Program Substudy Addendum 11 substudy 25-26: Tildrakizumab
- Conditions
- CancerAdvanced OsteosarcomaSoft Tissue SarcomaCancer - Any cancerCancer - Sarcoma (also see 'Bone') - soft tissueCancer - Other cancer types
- Registration Number
- ACTRN12620000984998
- Lead Sponsor
- The University of Sydney
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 32
Inclusion Criteria – molecular screening:
1. Male or female patients, aged 18 years and older, with pathologically confirmed advanced and/or metastatic cancer of any histologic type, including haematological cancers, or an earlier diagnosis of a poor prognosis cancer;
2. Sufficient and accessible tissue for molecular screening;
3. Patients receiving their last line of standard treatment or who have received and failed all standard anticancer therapy (where standard therapy exists) or have documented unsuitability for any further standard anticancer therapy. Poor prognosis cancers or cancers with low expected response rate to standard treatment (in the opinion of the investigator and based on available evidence) may be screened on an earlier line of treatment.
a. Failure is defined as either progression of disease (clinical or radiological) or intolerance to standard therapy resulting in the discontinuation of the therapy.
b. Documented unsuitability for further standard therapy includes known hypersensitivity, organ dysfunction or other patient factors that would make therapy unsuitable in the judgement of the responsible investigator;
4. Eastern Cooperative Oncology Group (ECOG) Performance Status performance status 0, 1 or 2;
5. Willing and potentially able to comply with study requirements, including treatment, timing and/or nature of required assessments; It is the intention to screen patients who are in principle wishing to take part in a MoST substudy if they are found to have an appropriate tumour biomarker and are still eligible for enrolment at the time of the treatment phase;
It is the intention to screen patients who are in principle wishing to take part in a MoST substudy if they are found to have an appropriate tumour biomarker and are still eligible for enrolment at the time of the treatment phase (substudy).
To be eligible for treatment in a substudy, patients must continue to meet all of the inclusion criteria and none of the exclusion criteria specified for entry into molecular screening at the time of registration to a treatment substudy. In addition, they must meet all the inclusion criteria and none of the exclusion criteria in the substudy addendum at the time of registration.
Inclusion Criteria – substudy:
1. Adults, aged 18 years and older, with pathologically confirmed advanced osteosarcoma or soft-tissue sarcoma;
2. Has measurable disease as defined by RECIST 1.1;
3. Confirmation of molecular eligibility by the molecular tumour board;
4. ECOG 0-2;
5. Sufficient and accessible tumour tissue for exploratory objectives
6. Received and failed all standard anticancer therapy or have documented unsuitability for any further standard therapy, if standard therapy exists;
7. Clinical or radiological progression on or following last anticancer therapy unless such anticancer therapy stopped due to toxicity / treatment intolerance;
8. Adequate organ system function as assessed by the following minimal laboratory requirements (within 7 days prior to first administration of study drug):
a. bone marrow function; platelets greater than or equal to 100 x 109/L, ANC greater than or equal to 1.5 x 109/L, and haemoglobin greater than or equal to 9g/dL (5.6mmol/L);
b. liver function; ALT/AST less than or equal to 3 x ULN (in the absence of liver metastases, less than or equal to 5 x ULN for patients with liver involvement)
and total bilirubin less than or equal to 1.5xULN;
c. renal functi
Exclusions criteria - molecular screening
1. Suitable for standard therapy or accepted standard care, if the patient has not been previously treated;
2. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may contraindicate participation and/or interact with the investigational product;
3. Other co-morbidities or conditions that may compromise assessment of key outcomes or in the opinion of the clinician, limit the ability of the patient to comply with the protocol;
4. For non central nervous system (CNS) cancers, patients with symptomatic CNS involvement of his/her cancer are excluded. Subjects with stable neurological function on stable doses of steroids/anti-epileptics over 4 weeks, and with no evidence of CNS progression within 12 weeks prior to screening are eligible;
5. History of another malignancy within 2 years prior to molecular screening registration are excluded unless adequately treated and determined free of progressive and metastatic disease for at least 6 months. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder can be included;
6. Pregnancy, lactation or inadequate contraception.
Exclusion criteria - substudy
1. Contraindications to investigational product;
2. Known history of hypersensitivity to active or inactive components of investigational product or latex;
3. Previous treatment with tildrakizumab (MK-3222) or other IL-23/Th-17 pathway inhibitors, including p40, p19, and IL-17 antagonists.
4. Specific co-morbidities or conditions (e.g. psychiatric) or concomitant medications which may interact with the investigational product(s);
5. Presence of any infection or history of recurrent infection requiring treatment with systemic antibiotics within 2 weeks prior to screening, or severe infection (e.g., pneumonia, cellulitis, bone, or joint infections) requiring hospitalization or treatment with intravenous antibiotics within 8 weeks prior to screening.
6. Co-morbidities or conditions that may compromise assessment of key outcomes or in the opinion of the clinician, limit the ability of the patient to comply with the protocol;
7. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment:
a. Radiation therapy, surgery or tumour embolization within 14 days prior to the first dose of study treatment. Palliative radiotherapy (for analgesia) is acceptable only if the irradiated field does not include target lesions;
b. Immunotherapy within 28 days prior to the first dose of study treatment;
c. Chemotherapy, biologic therapy, or hormonal therapy within 14 days or 5 half-lives of a drug prior to the first dose of study treatment or until recovery from previous therapy (whichever is longer);
8. Any unresolved toxicity ( greater than CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripheral neuropathy);
9. Any significant organ dysfunction or clinically significant laboratory abnormalities that place the subject at unacceptable risk for participation in a trial of an immunomodulatory therapy in the judgment of the investigator, within 6 months prior to screening.
10. Hospitalization due to an acute cardiovascular event, cardiova
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary outcome is to test the clinical activity of Tildrakizumab as measured by objective tumour response using FDG-PET/CT scans or the ratio of time-to-progression on study over the preceding period.[ FDG-PET/CT scans to measure objective tumour response will take place at: <br>Primary timepoint: Screening (within 14 days prior to registration)<br>Secondary Timepoints: During treatment, scans will be performed 8-weekly (every 2 cycles from start of treatment). During follow-up, scans will be performed every 8 weeks until progression.<br><br>]
- Secondary Outcome Measures
Name Time Method