A clinical trial assessing the addition of continuous ketogenic diet therapy to standard chemotherapy and immunotherapy treatment for patients with advanced squamous cell lung cancer

Not Applicable

• Conditions: ung cancer; Cancer

• Registration Number: ISRCTN73427832
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-07-15
• Last Update Posted: 26 August 2024
• Study Completion: 2027-07-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 48

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 < = 1.5 x upper limit of normal (ULN)
10.2. Alanine transferase (ALT) < = 2.5 x ULN.
10.3. Aspartate transferase (AST) < = 2.5 x ULN
11. Adequate renal function within 7 days of treatment:
11.1. Creatinine clearance <1.5 times ULN concurrent with creatine clearance >50 ml/min (calculated by Cockcroft and Gault equation). If this is <=50 ml/min then an isotopic Glomerular Filtration Rate (GFR) may be carried out and must be >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

1. Patients who do not meet the criteria of performance status <=1 on the ECOG Performance scale i.e. patients that are not be ambulatory and able to carry out work of a light or sedentary nature e.g. light housework, office work
2. Untreated symptomatic brain or leptomeningeal metastatic disease
3. Medical or psychiatric conditions compromising informed consent
4. Any pre-existing autoimmune disease besides well-controlled thyroid disease
5. Patients with active concurrent cancer or cancer within the past 3 years excepting non-melanomatous skin cancer and in situ cancers
6. Anyone diagnosed with fatty acid oxidation defects, organic acidurias (organic acid disorders), pyruvate carboxylase deficiency, porphyria or other disorders requiring a high carbohydrate treatment
7. Anyone who knows they respond to fasting by becoming significantly unwell or unconscious
8. Any disorder affecting the ability to eat or digest food; swallowing problems, digestive or reflux issues or difficulties with the bowel such as chronic constipation or diarrhoea
9. Patients requiring regular steroid therapy with steroids at a dose higher than prednisolone 10 mg/day or equivalent
10. History of anorexia
11. Diabetes on medication (Type 2 on oral medication - adjustment needed. Type 1 – not appropriate for trial)
12. Familial hyperlipidaemia
13. Acute pancreatitis or history of pancreatitis
14. Patients with a current or recent history of clinically significant renal, cardiac, hepatic, haematological, pulmonary, gastroenterological, cerebrovascular or neurological disease as determined by the investigator
15. Patients with a history of organ transplant including Allogeneic Stem Cell Transplantation (allo-SCT)
16. Patients with superior vena cava syndrome
17. No contraindications to anti-PD1 therapy or KDT, such as metabolic disorders
18. Carnitine deficiency (primary) and carnitine palmitoyltransferase I or II deficiency (myopathic form may present in adolescence) or carnitine translocase deficiency
19. Previous cholecystectomy
20. Osteopenia or osteoporosis
21. Corrected calcium > 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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.