Cancer Molecular Screening and Therapeutics (MoST) Program Substudy Addendum 7: Tremelimumab
- Conditions
- cancerCancer - Any cancer
- Registration Number
- ACTRN12620000918921
- Lead Sponsor
- The University of Sydney
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 22
To be eligible for treatment in this substudy, patients must meet all of the inclusion criteria below:
1. Adults, aged 18 years and older, with pathologically confirmed advanced or metastatic solid cancer of any histologic type or an earlier diagnosis of a poor prognosis cancer;
2. Measurable disease by iRECIST and RECIST or RANO
3. Confirmation of molecular eligibility by the molecular tumour board; (Tissue TMB >10m/mb on standard platforms (e.g. TSO500 panel, F1CDx) or >20m/mb on TST170 panel);
4. ECOG performance status 0, 1, 2;
5. Received and failed all standard anticancer therapy or have documented unsuitability for any further standard therapy, if standard therapy exists;
6. Clinical or radiological progression on or following last anticancer therapy unless such anticancer therapy stopped due to toxicity / treatment intolerance;
7. 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 greather 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. Bilirubin requirements will not apply to participants with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
c. renal function; serum creatinine less than or equal to 1.5xULN;
8. Tumour tissue sample available;
9. Sufficient and accessible tumour tissue for CTLA-4 testing and other correlative objectives;
10. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments
11. Signed, written informed consent to participation in the specific treatment substudy.
Exclusion criteria will include those relevant for screening but also include:
1. Contraindications to investigational product, as listed in the substudy addendum and outlined in the Investigator Brochure appended to each substudy module;
2. Known history of hypersensitivity to active or inactive components of investigational product;
3. Previous treatment with the same agent or same class of agent;
4. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may interact with the investigational product(s);
5. 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;
6. 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);
7. 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);
8. Administration of any investigational treatment within 30 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study treatment;
9. 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;
10. 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;
11. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception;
12. Patients with bladder cancer or pancreatic cancer
13. Eligible for participation in another MoST substudy based on identification of an actionable mutation. However, patients who have previously participated in another MoST substudy may subsequently participate in this study, only if all other inclusion and exclusion criteria are satisfied;
14. Participation in another clinical study with an investigational product during the last 4 weeks prior to study enrolment;
15. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary end point is the progression-free survival at 6 months (PFS). PFS is defined as the interval from date of registration to the date of first evidence of disease progression or death from any cause, whichever occurs first. Participants who did not progress or die will be censored on the date of their last clinical assessment or tumour assessment.<br>Disease progression is defined according to RECIST v1.1, RANO guidelines or clinical progression. Clinical progression is defined as the development of symptoms attributable to cancer progression or initiation of other anticancer treatment for cancer. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be considered to have progressed at the time of commencement of subsequent therapy. [ Tumour progression will be monitored by CT scans (or other imaging as appropriate) and GCIG and PCWG2 criteria every 12 weeks. ]
- Secondary Outcome Measures
Name Time Method