None listed
Conditions
Brief summary
This is a substudy of the Cancer Molecular Screening and Therapeutics (MoST) Program, which is registered on ANZCTR with ID ACTRN12616000908437. This substudy will evaluate the activity of tremelimumab treatment in combination with durvalumab followed by single durvalumab treatment in patients with advanced cancers and tumours. Who is it for? All participants in this study must have completed screening as part of the Cancer Molecular Screening and Therapeutics (MoST) Program (ACTRN12616000908437), and been identified as having having no actionable molecular targets. Study details All participants in this study will take the intravenous drugs tremelimumab plus durvalumab once every 28 day cycle. From week 16 of treatment durvalumab will be administered alone once every 28 days. Treatment will continue until progression, unacceptable toxicity or withdrawal. Retreatment will be discussed with you by your doctor. All participants will undergo assessments at 8 weekly intervals or as clinically indicated in order to evaluate tumour response, safety and tolerability of treatment, health related quality of life during treatment, and overall survival. 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 palbociclib will be well tolerated and will improve outcomes for future patients, however, there may be no clear benefit from participation in this study.
Interventions
Patients weighing 30 kg or more will receive a combination of a fixed dose of 1500 mg durvalumab via intravenous infusion followed by a 75 mg tremelimumab intravenous infusion every 4 weeks (28 days) for up to 4 doses/cycles. After this, treatment will continue with 1500 mg durvalumab every four weeks (28 days) starting on Week 16 for up to 9 doses.
Retreatment is allowed (once only) for patients meeting the retreatment criteria below:
1. Patients who achieve and maintain disease control (ie,
Patients weighing 30 kg or more will receive a combination of a fixed dose of 1500 mg durvalumab via intravenous infusion followed by a 75 mg tremelimumab intravenous infusion every 4 weeks (28 days) for up to 4 doses/cycles. After this, treatment will continue with 1500 mg durvalumab every four weeks (28 days) starting on Week 16 for up to 9 doses. Retreatment is allowed (once only) for patients meeting the retreatment criteria below: 1. Patients who achieve and maintain disease control (ie, CR, PR, or SD) through to the end of the 12-month treatment period may restart treatment with the combination upon evidence of PD, with or without confirmation according to RECIST 1.1, during follow-up. 2. Patients who complete the 4 dosing cycles of the combination of durvalumab and tremelimumab portion of the regimen (with clinical benefit per Investigator judgment), but subsequently have evidence of PD during the durvalumab monotherapy portion of the combination regimen, with or without confirmation according to RECIST 1.1, may restart treatment with the combination. Total treatment on this study will be approximately two years with further treatment to be discussed with the treating clinician. Participating institutions will maintain a record of drug dispensed for each patient.
Sponsors
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 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. 1. Confirmation of molecular eligibility by the molecular tumour board; 2. Received and failed all standard anticancer therapy or have documented unsuitability for any further standard therapy, if standard therapy exists; 3. Clinical or radiological progression on or following last anticancer therapy; 4. Adequate organ system function per addendum definitions 5. Meet any additional inclusion criteria specified in the relevant substudy addendum; 6. Signed, written informed consent to participation in the specific treatment substudy. Inclusion criteria specific to this sub-study: 1. ECOG performance status of 0 or 1 2. Sufficient and accessible tumor tissue for PD-L1 testing and exploratory objectives 3. Adequate liver function. See protocol definition. 4. Serum creatinine CL greater than 40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.
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. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment: o 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; o Immunotherapy within 28 days prior to the first dose of study treatment; o 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); 5. Administration of any investigational treatment within 30 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study treatment; 6. Any additional exclusion criteria specified in the relevant substudy addendum. Exclusion Criteria specific to the sub-study: 1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 2. Patients with cutaneous melanoma, non-small cell lung cancer, squamous cell carcinoma of the head and neck, bladder cancer, thymoma, thymic carcinoma or pancreatic cancer 3. Patients who are eligible for other clinical studies involving durvalumab and/or tremelimumab 4. Eligible for participation in another MoST substudy based on identification of an actionable mutation. Patients who have previously participated in another MoST substudy may subsequently participate in this study, all other inclusion and exclusion criteria being satisfied 5. Participation in another clinical study with an investigational product during the last 4 weeks prior to study enrolment 6. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA-4, including tremelimumab 7. Any unresolved toxicity (>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, peripherally neuropathy) 8. Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia’s Correction 9. Prolonged use of moderate to high doses of immunosuppressive medication before the first dose of durvalumab or tremelimumab. Exceptions include intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses (eg: <=10 mg/day of prednisone); use of dexamethasone up to 4mg /day within 14 days of initial treatment for patients with brain tumours. 10. Any prior Grade =3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1 11. Active autoimmune disease or prior documented autoimmune disease requiring systemic treatment within the past 2 years NOTE: Subjects with vitiligo, Grave’s disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. 12. Active or prior documented inflammatory bowel disease requiring systemic treatment within the past 2 years (e.g., Crohn’s disease, ulcerative colitis) 13. History of primary immunodeficiency 14. History of allogeneic organ transplant 15. History of hypersensitivity to durvalumab or tremelimumab or any excipient 16. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject 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 subject to give written informed consent 17. Known history of active tuberculosis 18. History of leptomeningeal carcinomatosis 19. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab
Outcome results
None listed