Adrenocortical carcinoma Cancer
Conditions
Interventions
This clinical trial has 2 phases (Phase 2A and Phase 2B). It is a Phase II multi-centre open-label randomized dose-optimisation and single-arm dose expansion trial design
In Phase 2A, a total of 16 e
however, this depends on whether there are enough supplies of CY-101. It is expected that after this, CY-101 will be permanently discontinued.
If a participant is withdrawn from the trial, the trial
Sponsors
Cancer Research UK
Eligibility
Sex/Gender
All
Age
16 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Written (signed and dated) informed consent and be capable of co-operating with CY-101 administration and follow-up. 2. Histologically confirmed ACC that is either locally advanced and not amenable to surgical resection or metastatic, with evidence of disease progression post the most recent line of therapy. 3. Participants must have received treatment with at least 1 line, but not more than 2 prior lines, of systemic therapy for established locally advanced or metastatic disease, and must have received mitotane therapy within these lines of therapy for advanced/metastatic disease (or as neoadjuvant/adjuvant therapy). Participants must have relapsed within 1 year of neoadjuvant/adjuvant therapy for this to be considered a line of treatment. 4. At least 1 lesion that is objectively evaluable or measurable, according to itRECIST. Previously irradiated lesions cannot be counted as target lesions unless they have clearly progressed after radiotherapy. Participants also require at least 1 separate lesion(s) amenable for IT injection by a clinician or interventional radiologist under ultrasound-assisted guidance. Refer to protocol for further details. 5. Adequate tissue available for biomarker testing, from either archival tissue or pre-treatment biopsy. 6. Life expectancy of =12 weeks. 7. Eastern Cooperative Oncology Group performance status of 0-2. 8. Haematological and biochemical indices within the prescribed ranges. 9. Aged 16 years or over at the time consent is given.
Exclusion criteria
Exclusion criteria: 1. Radiotherapy (except for palliative reasons), endocrine therapy, chemotherapy or other Investigational Medicinal Products (IMPs) during the previous 28 days before the first dose of CY-101. Continued treatment with mitotane during the trial to control hormonal symptoms is permitted under certain conditions as specified in the trial protocol. Mitotane plasma level monitoring is to be maintained and documented during the trial. 2. Prior treatment with a Wnt inhibitor. 3. Ongoing toxic manifestations of previous treatments greater than Common Terminology Criteria for Adverse Events Grade 1 (other than alopecia of any grade or Grade 2 peripheral neuropathy). Exceptions apply. 4. Any central nervous system metastases (unless patients had local therapy and are asymptomatic, radiologically stable for 4 weeks and off steroids for the last 4 weeks). 5. Women who are pregnant or breastfeeding (or planning to breastfeed). 6. Women of childbearing potential. However, those patients who are not already pregnant or breastfeeding (or planning to breastfeed) are eligible, provided they have a negative highly sensitive serum pregnancy test =7 days before trial entry and agree to follow the trial’s contraceptive requirements. 7. Male patients with partners of childbearing potential. However, those patients who agree to follow the trial’s contraceptive requirements are eligible. 8. Major surgery from which the patient has not yet recovered. 9. At high medical risk because of non-malignant systemic disease, including active uncontrolled infection. 10. Serologically positive for hepatitis B virus or hepatitis C virus (HCV). Patients with previous HCV exposure but no current infection are eligible. 11. Known untreated human immunodeficiency virus (HIV) infection. Patients on established antiretroviral medication and who have well-controlled HIV infection/disease are eligible, provided they meet protocol-specified criteria. 12. Allergy or hypersensitivity to any of the ingredients/excipients in the CY-101 formulation. 13. Significant cardiovascular disease. As defined in the trial protocol. 14. Extensive radiotherapy to >25% of bone marrow within 12 weeks prior to the first dose of CY-101. 15. Participating in or plans to participate in another interventional clinical trial whilst taking part in this trial of CY-101. See protocol for more information. 16. Current malignancies of other types, with certain exceptions as per the trial protocol. Cancer survivors who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for =5 years and are deemed at negligible risk for recurrence are eligible for the trial. 17. Any congenital immunodeficiency syndrome. 18. Active autoimmune disease that has required systemic treatment in the 2 years before trial entry. 19. Use of systemic corticosteroids (apart from replacement doses for endocrinopathy up to an equivalent of 10 mg QD prednisolone or 20 mg QD prednisolone if receiving mitotane concurrently). 20. Prior adverse reaction to cancer immunotherapy that required intravenous steroid treatment or other immunosuppressive treatment. 21. Live, attenuated vaccine within 28 days before the first dose of CY-101. 22. Evidence of bleeding diathesis, or anticoagulant or antiplatelet therapy (excluding prophylactic low molecular weight heparin or low-dose aspirin). 23. High burden of metastatic disease defined as =4 organs involved with metastases or greater than 12 individual
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase IIa: Determining an optimal dose of CY-101 based upon review of all clinically relevant data including but not limited to toxicity, efficacy, quality of life data and PK parameters at the end of Phase IIa and EoT Phase IIb: Overall Response Rate (ORR) defined as the proportion of participants who achieve complete response (CR) or partial response (PR) according to intratumoural immunotherapy Response Evaluation Criteria in Solid Tumours (itRECIST) at the end of the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase 2a and 2b 1. Frequency and causality of adverse events, including relatedness, seriousness and severity graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 assessed at the end of Phase IIa and end of trial. 2. Participant reported quality of life outcomes using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 assessed at the end of Phase IIa and end of trial. 3. PK parameters including, where possible, maximum concentration, area under the curve, time to reach maximum concentration, terminal elimination half-life, clearance and volume of distribution assessed at the end of Phase IIa and end of trial. Phase 2b 4. ORR defined as the proportion of participants who achieve immune complete response (iCR) or immune partial response (iPR) according to immune-related Response Evaluation Criteria in Solid Tumours (iRECIST) assessed at the end of trial. 5. Duration of response defined as the time from date of first confirmed CR or PR according to itRECIST, or iCR or iPR according to iRECIST, to date of disease progression or death from any cause assessed at the end of trial. 6. Disease control rate defined as best response of CR, PR or stable disease =12 weeks according to itRECIST and iCR, iPR or immune stable disease =12 weeks according to iRECIST assessed at the end of trial. 7. Progression free survival (PFS) defined as the time from date of first dose of CY-101 to date of disease progression or date of death from any cause assessed at the end of trial. 8. PFS at 18 weeks assessed at the end of trial. 9. Overall Survival (OS) defined as time from date of first dose to date of death from any cause assessed at the end of trial. 10. OS at 6 and 12 months assessed at the end of trial. 11. Growth modulation index defined as the ratio of PFS on trial to PFS from previous treatment assessed at the end of trial. 12. Time to next treatment defined as | — |
Countries
England, United Kingdom
Contacts
Public ContactLesley McGuigan
Outcome results
None listed