Lung cancer Cancer
Conditions
Interventions
Treatment will consist of standard-of-care chemo/immunotherapy paclitaxel/carboplatin/pembrolizumab for four (21 days) together with continuous ketogenic diet therapy (KDT) with an introductory week p
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically proven locally advanced or metastatic squamous cell lung cancer not amenable to definitive local therapy and suitable for first-line systemic therapy of chemo-immunotherapy (paclitaxel, carboplatin, pembrolizumab) 2. Aged 16 years or older 3. Willing to undertake dietary modification for up to 12 weeks (+ 1 week introductory period) 4. Willing to self-monitor blood glucose and ketones daily and feedback/discuss weekly 5. Life expectancy greater than trial treatment period >12 weeks 6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 with no deterioration over the previous 2 weeks 7. Disease measurable according to RECIST v1.1 8. Disease amenable to biopsy for metabolic studies 9. Adequate haematological function within 7 days of treatment 9.1. Haemoglobin > = 100 g/L 9.2. Absolute neutrophil count (ANC) > = 1.5 x 10^9/L 9.3. Platelet count > = 100 x 10^9/L 10. Adequate hepatic function within 7 days of treatment: 10.1. Total serum bilirubin 50 ml/min (calculated by Cockcroft and Gault equation). If this is 50 ml/min 12. Willing to accept paired biopsies at week 5 and blood samples at pre- and post- 12 weeks KDT treatment for translational metabolic analyses 13. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal participants 14. Male and female participants of childbearing potential willing to use highly effective contraception 15. Willing and able to comply with scheduled visits, treatment plan and other trial procedures 16. Willing and able to give written informed consent for the trial
Exclusion criteria
Exclusion criteria: 1. Patients who do not meet the criteria of performance status ULN within 7 days of treatment 21.1. Corr. Calcium = Total Calcium (mmol/L) + ([40 – Albumin (G/L)] x 0.02) 22. Phosphate > ULN within 7 days of treatment 23. Hepatic function (in patients with liver metastasis) 23.1. Alanine transferase (ALT) and Aspartate transferase (AST) >5 x ULN 24. Patient is positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA (qualitative) is detected); patients with negative Hepatitis C antibody testing may not need RNA testing 25. Known history of tuberculosis 26. Female patients of childbearing potential should be using adequate contraceptive measures, should not be breastfeeding and must have a negative pregnancy test prior to the start of treatment. Pregnant patients will be ineligible 27. Patient has an active infection requiring therapy 28. Patient is, at the time of signing informed consent, a regular user (including “recreational use”) of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol) 29. Participation in another therapeutic clinical trial whilst taking part in this trial 30. Any psychological, familial, sociological or geographical condition hampering protocol compliance 31. Any medical condition which in the opinion of the Investigator would compromise the ability of the patient to participate in the trial or which wo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Compliance to maintain experimental Ketogenic diet therapy (KDT) for a minimum of 6 weeks and maintaining therapeutic ketosis for a minimum of 6 weeks (after a 1-week introductory period). This will be measured by returning at least 85% of Glucose-Ketone Index (GKI) measurements =3.0 from glucose monitoring and twice-daily ketone finger-prick blood tests. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Compliance to maintain experimental ketogenic diet therapy (KDT) associated therapeutic ketosis for a minimum of 12 weeks. This will be measured by returning at least 85% of GKI measurements =3.0 (from glucose monitoring and twice-daily ketone finger-prick blood tests) 2. Overall patient-reported adherence to KDT over 6 and 12 weeks determined from responses on a visual analogue scale in the patients’ daily food diaries 3. Overall patient-reported adherence to KDT over 6 and 12 weeks determined by dietitian review of patients’ daily food diaries and recorded as a response on a visual analogue scale on the case report form 4. Overall patient-reported tolerability to KDT over 6 and 12 weeks, determined from responses on a visual analogue scale in the patients’ daily food diaries 5. Acceptability, feasibility and tolerability of KDT for both participants and professionals will also be assessed through an optional embedded qualitative process evaluation at the end of the trial 6. Health-related quality of life will be generated from patient completion of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire (15 measures) and EQ-5D-5L questionnaire (2 measures) at multiple points over time. This will be assessed at the beginning of every cycle of treatment and at the beginning and end of the maintenance period. 7. Qualitative process evaluation interviews will be used to identify meaningful lifestyle changes in participants at the end of the trial 8. Occurrence of an objective response (as measured by RECIST 1.1) from the patient's scans after each standard of care scan during trial treatment and follow-up (every 9-12 weeks) 9. Occurrence of durable clinical benefit (DCB), defined as being free of disease progression for at least 6 months from the start of trial treatment. 10. Progression-free survival time, defined as the time in whole days from the date of registration to the date of the first documented evidence of disease pr | — |
Countries
England, United Kingdom, Wales
Contacts
Public ContactJoshua Savage
Outcome results
None listed