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

NCT03153280 | Terminated Phase 1 DMC

• 2 other identifiers: CTRIAL-IE (ICORG) 11-322014-000186-47
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a phase Ib, open label, multi-centre trial designed to estimate the Maximum Tolerated Dose (MTD) of lithium when combined with a standard chemotherapy regimen of oxaliplatin and capecitabine in patients with advanced, unresectable, oesophago-gastric or colorectal cancer who have received no previous treatment for advanced disease (previous adjuvant or neo-adjuvant treatment is acceptable if completed at least 6 months prior to registration). The study follows a modified Fibonacci, 3+3, dose escalation design. Patients are enrolled in cohorts of 3. All three patients in each cohort must complete at least two cycles of treatment to be evaluable for toxicity. If a patient cannot complete 2 cycles, another patient will be enrolled.

Conditions

Colorectal Neoplasms; Stomach Neoplasm; Esophageal Neoplasms

Outcome Measures

Primary Outcomes (1)

• Incidence of dose limiting toxicity (DLT) within the two first cycles at each dose level.

  The MTD will be based on the incidence of DLT within the two first cycles of lithium in combination with standard chemotherapy of oxaliplatin and capecitabine at each dose level.

  26 months

Secondary Outcomes (3)

• Progression Free Survival (PFS) as defined by RECIST Criteria Version 1.1.

  3 years

• Objective Response Rate (ORR) as defined by RECIST Criteria Version 1.1.

  3 years

• Incidence of adverse events reported as per the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. (Safety and Tolerability).

  3 years

Study Arms (1)

Lithium, Oxaliplatin & Capecitabine

EXPERIMENTAL

Target serum concentrations of escalating doses of lithium (0.6, 0.9, 1.26 or 1.4 mmol/L) in combination standard chemotherapy - oxaliplatin and capecitabine.

Drug: Lithium; Drug: Oxaliplatin; Drug: Capecitabine

Interventions

Lithium DRUG

Dose escalation of Lithium to determine the maximum tolerated dose (MTD)

Lithium, Oxaliplatin & Capecitabine

Oxaliplatin DRUG

Dose as used in standard of care - 130 mg/m2.

Lithium, Oxaliplatin & Capecitabine

Capecitabine DRUG

Dose as used in standard of care - 800 - 1000 mg/m2

Lithium, Oxaliplatin & Capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be given according to ICH/GCP and national/local regulations, and be obtained prior to any study-related procedures.
• Histologically or cytologically confirmed adenocarcinoma of the colon, rectum, stomach, gastro-oesophageal junction or lower third of the oesophagus.
• Metastatic disease not amenable to surgical resection with curative intent.
• Eastern Co-operative Oncology Group (ECOG) performance status 2 (Appendix B).
• Age ≥ to 18.
• Estimated life expectancy ≥ 3 months.
• 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).
• 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
• Normal thyroid function (TSH 0.4-3.5mUL).
• Able to swallow and retain oral medication.
• 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.
• Women of child bearing potential must have pregnancy excluded by urine or serum beta-HCG testing within 7 days prior to registration.

You may not qualify if:

• 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).
• 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.
• Brain or other Central Nervous System (CNS) metastases.
• Known di-hydropyrimidine dehydrogenase (DPD) deficiency.
• Screening electrocardiogram (ECG) with evidence of:
• QT prolongation (QTc \> 450 ms in males and \> 470 ms in females)
• nd or 3rd degree heart block
• Other severe cardiac dysfunction (ECG must be assessed for all patients within 14 days prior to registration)
• Clinically significant cardiovascular disease including:
• Cerebrovascular accident within 6 months prior to registration
• Myocardial infarction within 6 months prior to registration
• Uncontrolled angina
• Uncontrolled hypertension
• Clinically significant valvular disease
• Congestive Heart Failure (NYHA Class 2) (See Appendix E).

Sponsors & Collaborators

• Cancer Trials Ireland: lead
• University College Cork: collaborator

Study Sites (2)

Cork University Hospital

Cork, Ireland

Location

St James's Hospital

Dublin, Ireland

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Stomach Neoplasms; Esophageal Neoplasms

Interventions

Lithium; Oxaliplatin; Capecitabine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Cancer Trials Ireland Dublin 11, Ireland

  Cancer Trials Ireland

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Lithium: starting dose: 2x 400mg p.o. per day. Initial target blood concentration (Level 1 = 0.6mmol/L). Oxaliplatin: 130 mg/m2 in 500 ml normal saline (NS) over 120 minutes on Day 1 of each 3 week cycle. Capecitabine: 1000 mg/m2 b.i.d po on Days 1 to 14 of each 3 week cycle.

Study Record Dates

• First Submitted: May 10, 2017
• First Posted: May 15, 2017
• Study Start: January 13, 2022
• Primary Completion: September 7, 2023
• Study Completion: September 7, 2023
• Last Updated: July 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IE (2)