None listed
Conditions
Brief summary
This study will determine if an immunotherapy drug (called tremelimumab) has an effect on progression-free survival in patients with rare or neglected cancers. This is a substudy of the Cancer Molecular Screening and Therapeutics (MoST) Program, which is registered on ANZCTR with ID ACTRN12616000908437. Who is it for? You may be eligible for this study if you are an adult with and advanced and/or metastatic solid cancer. Study details Participants will receive the study drug (Tremelimumab) via intravenous infusion every 4 weeks for 6 cycles. Participants will complete imaging, clinical and safety assessments throughout the study. We cannot guarantee that patients will receive any benefits from this study. This study is being carried out to improve the way we treat cancer patients who may have limited treatment options available to them. It is hoped that tremelimumab will be well tolerated and will improve outcomes for future patients, however, there may be no clear benefit from participation in this study
Interventions
A group of 24 patients will be treated with tremelimumab.
Patients will be treated with a fixed dose of 10 mg/kg tremelimumab via intravenous infusion every 4 weeks for 6 cycles.
Participants will be followed up for at least 90 days after end of treatment for new adverse events and to follow up any adverse events which are ongoing at the end-of-treatment visit.
Patients will be followed up for overall survival or subsequent anticancer treatments at 12 weekly intervals post progression.
A pa
A group of 24 patients will be treated with tremelimumab. Patients will be treated with a fixed dose of 10 mg/kg tremelimumab via intravenous infusion every 4 weeks for 6 cycles. Participants will be followed up for at least 90 days after end of treatment for new adverse events and to follow up any adverse events which are ongoing at the end-of-treatment visit. Patients will be followed up for overall survival or subsequent anticancer treatments at 12 weekly intervals post progression. A patient who has been receiving the study treatment - tremelimumab and is deemed to be clinically benefiting despite unconfirmed progression (iUPD per iRECIST) in the event of suspected pseudoprogression may continue tremelimumab at the discretion of the treating investigator. In this case, a confirmatory follow-up scan no later than the next imaging visit (no less than 8 weeks) is warranted per iRECIST. No dose reductions and/or dose escalations of tremelimumab are permitted. The management of immune and non-immune related adverse events will be managed by the site and MoST team.
Sponsors
The University of Sydney
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
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 interventional study; 16. Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab or an anti- CTLA-4, including tremelimumab; 17. Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3 electrocardiograms (ECGs), approximately 30 minutes apart using Fredericia’s Correction 18. Any prior Grade greater than or equal to 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE greather than Grade 1; 19. Prolonged use of moderate to high doses of immunosuppressive medication before the first dose of tremelimumab. Exceptions include intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses (eg. less than 10 mg/day of prednisone; use of dexamethasone up to 4mg /day within 14 days of initial treatment for patients with brain tumours); 20. Active autoimmune disease or prior documented autoimmune disease requiring systemic treatment within the past 2 years NOTE: Participants with vitiligo, alopecia or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded; 21. Active or prior documented inflammatory bowel disease requiring systemic treatment within the past 2 years (e.g., Crohn’s disease, ulcerative colitis); 22. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of tremelimumab. Note: Local surgery of isolated lesions for palliative intent is acceptable. 23. History of primary immunodeficiency; 24. History of allogeneic organ transplant; 25. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, Interstitial lung disease, active peptic ulcer disease or gastritis, active bleeding diatheses including any participants known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the participants to give written informed consent; 26. Known history of active tuberculosis; 27. History of leptomeningeal carcinomatosis; 28. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving tremelimumab.
Outcome results
None listed