Temozolomide and nivolumab as a treatment for cancer of the gullet
- Conditions
- Oesophagogastric cancerCancer
- Registration Number
- ISRCTN11398887
- Lead Sponsor
- niversity of Southampton
- Brief Summary
2022 Protocol article in https://pubmed.ncbi.nlm.nih.gov/36050653/ protocol (added 08/03/2023)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 18
1. Patients =18 years of age
2. Pathologically confirmed advanced unresectable or metastatic OGA
3. Loss of MGMT protein on IHC
4. Mismatch repair proficient (MSI-normal or MMR intact)
5. Previously treated with at least 3 months of platinum and fluoropyrimidine-based chemotherapy for advanced disease and suitable for maintenance therapy
6. Measurable disease per RECIST 1.1 and iRECIST guidelines
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
8. Can swallow TMZ capsules
9. Adequate organ function assessed within 7 days before randomization
10. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to randomization
1. Previous treatment with TMZ
2. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
3. Active central nervous system metastases
4. Candidate for curative surgery
5. Previous malignancies are excluded unless a complete remission was achieved at least 5 years prior to study entry. Adequately treated cervical carcinoma in situ, and localized non-melanoma skin cancer are not exclusion criteria, regardless of time point of diagnosis.
6. Active, known, or suspected infectious or autoimmune disease (except for patients with Type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enrol)
7. Conditions requiring systemic treatment with either corticosteroids (=10 mg daily prednisolone or equivalent) or other immunosuppressive medications within 14 days of study drug administration
8. Interstitial lung disease
9. > Grade 1 peripheral neuropathy
10. Positive test result for HBV or HCV indicating acute or chronic infection
11. Known history of testing positive for HIV or known AIDS
12. Known hypersensitivity to the components or excipients of co-trimoxazole, temozolomide or nivolumab. (Please refer to nivolumab IB and SmPC for TMZ and co-trimoxazole)
13. Known hypersensitivity to dacarbazine (DTIC)
14. Clinically significant abnormal 12-lead ECG. If clinically indicated, cardiac function assessment using either echocardiography or MUGA Scan, if clinically significant the patient is ineligible
15. In the past 6 months serious cardiac illness or medical condition including but not confined to:
15.1. History of documented congestive heart failure (CHF)
15.2. High-risk uncontrolled arrhythmias
15.3. Angina pectoris requiring antianginal medication
15.4. Clinically significant valvular heart disease
15.5. Evidence of transmural infarction
15.6. Poorly controlled hypertension (e.g. systolic >180 mmHg or diastolic greater than 100 mmHg)
16. Patients with severe liver parenchymal damage
17. Patients with severe renal insufficiency where repeated measurements of the plasma concentration cannot be performed
18. Patients with a history of drug-induced immune thrombocytopenia with the use of trimethoprim and/or sulfonamides
19. Patients with acute porphyria
20. Patients with severe myelosuppression
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Objective response rate to nivolumab measured using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and iRECIST at 24 months
- Secondary Outcome Measures
Name Time Method