Dose Escalation Study of Lithium With Oxaliplatin and Capecitabine in Advanced Oesophago-Gastric or Colorectal Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 23 October 2023
• Main ID: NCT03153280
• Date of registration: 10/05/2017
• Prospective Registration: Yes
• Primary sponsor: Cancer Trials Ireland
• Public title: Dose Escalation Study of Lithium With Oxaliplatin and Capecitabine in Advanced Oesophago-Gastric or Colorectal Cancer Lithium
• Scientific title: A Phase Ib, Dose Escalation Study of Lithium When Added to Standard Chemotherapy of Oxaliplatin and Capecitabine in Patients With Advanced Oesophago-Gastric or Colorectal Cancer
• Date of first enrolment: January 13, 2022
• Target sample size: 2
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03153280
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Ireland

Contacts

• Name: Cancer Trials Ireland Dublin 11, Ireland
• Affiliation: Cancer Trials Ireland

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Written informed consent must be given according to ICH/GCP and national/local
regulations, and be obtained prior to any study-related procedures.

2. Histologically or cytologically confirmed adenocarcinoma of the colon, rectum,
stomach, gastro-oesophageal junction or lower third of the oesophagus.

3. Metastatic disease not amenable to surgical resection with curative intent.

4. Eastern Co-operative Oncology Group (ECOG) performance status 2 (Appendix B).

5. Age = to 18.

6. Estimated life expectancy = 3 months.

7. Measurable disease, defined as at least 1 uni-dimensionally measurable lesion on a CT
scan as defined by RECIST criteria, Version 1.1 (Appendix F).

8. Adequate haematological, hepatic, and renal function defined as:

a. Renal: i. Calculated creatinine clearance (CrCl) 50ml/min (see Appendix G) b. Liver
function tests: i. Total Bilirubin = ULN ii. ALT and AST = 2.5 x ULN (= 5 x ULN with
liver involvement of their cancer) iii. Alkaline Phosphatase = 2.5 x ULN (= 5 x ULN
with liver involvement of their cancer) c. Haematology: i. Haemoglobin 9.0 g/dL for
females and 10.0 g/dL for males ii. Absolute neutrophil count 1.5 x 109/L iii.
Platelet count 100 x109/L

9. Normal thyroid function (TSH 0.4-3.5mUL).

10. Able to swallow and retain oral medication.

11. Women of child-bearing potential and male patients must agree to use adequate
contraception for the duration of study participation and for up to 3 months following
discontinuation of therapy. Adequate contraception is defined as any medically
recommended (or combination of methods) as per standard of care.

12. Women of child bearing potential must have pregnancy excluded by urine or serum
beta-HCG testing within 7 days prior to registration.

Exclusion Criteria:

1. Received prior chemotherapy for metastatic disease. (Patients who received prior
adjuvant or neo-adjuvant chemotherapy or definitive radio-chemotherapy for localised
disease are eligible if the chemotherapy has stopped at least 6 months before
registration).

2. Previous or concurrent malignancy within the past 5 years, with the exception of basal
cell carcinoma of the skin or in-situ neoplasia of the uterine cervix or bladder.

3. Brain or other Central Nervous System (CNS) metastases.

4. Known di-hydropyrimidine dehydrogenase (DPD) deficiency.

5. Screening electrocardiogram (ECG) with evidence of:

1. QT prolongation (QTc > 450 ms in males and > 470 ms in females)

2. 2nd or 3rd degree heart block

3. Other severe cardiac dysfunction (ECG must be assessed for all patients within 14
days prior to registration)

6. Clinically significant cardiovascular disease including:

1. Cerebrovascular accident within 6 months prior to registration

2. Myocardial infarction within 6 months prior to registration

3. Uncontrolled angina

4. Uncontrolled hypertension

5. Clinically significant valvular disease

6. Congestive Heart Failure (NYHA Class 2) (See Appendix E).

7. Severe chronic obstructive pulmonary disease (COPD) > Grade 2 according to NCI CTCAE
v4.0.

8. Known history or family history of Brugada Syndrome.

9. Symptoms or signs of peripheral neuropathy.

10. Ongoing infection > Grade 2 according to NCI CTCAE v4.0.

11. Seizure disorder requiring medication.

12. Dehydration Grade 1 according to NCI CTCAE v4.0; patients on Low sodium diet;
Addison's disease.

13. Known hypersensitivity to lithium, oxaliplatin or fluoropyrimidines.

14. Pregnant or nursing women.

15. Concurrent treatment with any other investigational agents within 30 days prior to
registration.

16. Any psychological, physical, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule;
(those conditions should be discussed with the patient before registration in the
trial).

17. Unable or unwilling to discontinue (and substitute if necessary) use of prohibited
medications for at least 30 days prior to and for the duration of study treatment (see
section 7.5 for a description of prohibited medications).

18. Patients weighing less than 50kg.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Esophageal Neoplasms

Colorectal Neoplasms

Stomach Neoplasm

Intervention(s)

Drug: Lithium

Drug: Oxaliplatin

Drug: Capecitabine

Primary Outcome(s)

Incidence of dose limiting toxicity (DLT) within the two first cycles at each dose level. [Time Frame: 26 months]

Secondary Outcome(s)

Objective Response Rate (ORR) as defined by RECIST Criteria Version 1.1. [Time Frame: 3 years]

Progression Free Survival (PFS) as defined by RECIST Criteria Version 1.1. [Time Frame: 3 years]

Incidence of adverse events reported as per the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. (Safety and Tolerability). [Time Frame: 3 years]

Secondary ID(s)

2014-000186-47

CTRIAL-IE (ICORG) 11-32

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

University College Cork