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

July 3, 2025 updated by: Cancer Trials Ireland

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study is a Phase Ib, open label, multi-centre, dose escalation trial to assess the dose of lithium that can be safely combined with standard treatment oxaliplatin and capecitabine chemotherapy.

Registered patients will be treated with lithium combined with a standard chemotherapy regimen of oxaliplatin and capecitabine until a maximum of 6 x 21 day cycles (18 weeks), tumour progression, unacceptable toxicity, pregnancy, withdrawal of consent or withdrawal at the discretion of the investigator, whichever occurs first.

After discontinuation of study treatment, all patients will be followed for safety for at least 30 days.

Patients who discontinue treatment for reasons other than disease progression will continue to be followed every 9 weeks in accordance with standard of care for efficacy (i.e. tumour assessment) until disease progression, death, withdrawal of consent, loss to follow up or until the start of a new anti-neoplastic treatment, whichever occurs first.

Once the patient has documented disease progression, they will be followed up every three months (±1 month) for survival status.

The trial will be a traditional 3+3 design: cohorts of 3 patients will be treated with lithium combined with standard treatment oxaliplatin and capecitabine chemotherapy.

The doses of oxaliplatin and capecitabine have been established in prior phase II and III studies and will not be escalated. Lithium target serum concentrations are assigned at registration according to a defined dose escalation scheme. Study lithium dose escalation will follow a modified Fibonacci 3+3 sequence.

A -1 dose level (0.4mmol/L) is included in case dose de-escalation is needed.

The levels of lithium achieved in each patient will be established by regular assessment of steady state serum concentrations.

Lithium will start at a low level and dose escalations will be performed in cohorts of 3 patients according to a standard 3+3 algorithm.

Dose escalation and determination of MTD will be based on the occurrence of Dose Limiting Toxicities (DLT) as defined below.

The first cohort of 3 patients will commence at dose level 1. All patients in each cohort will be observed for two cycles on the specified dose:

  • If none of 3 patients at a given dose level experiences a DLT, accrual will continue to the next dose level according to the protocol.
  • If 1 of 3 patients experiences a DLT at a given dose level, 3 additional patients will be treated at the same dose. If no additional patient has a DLT in this cohort, accrual will continue to the next dose level according to the protocol.
  • If 2 or more patients in 3 or 6 patients treated at a given dose experience a DLT, the next lowest dose level will define the MTD.

A Dose Limiting Toxicity (DLT) is defined as any of the following adverse events occurring during the two first cycles (within 42 days from first dose) of treatment and possibly, probably or definitely related to the combination of lithium, oxaliplatin and capecitabine:

A. Grade 3 or 4 non-haematological toxicity other than nausea, vomiting or fatigue.

B. Grade 3 or 4 thrombocytopenia: grade 4 thrombocytopenia (platelet count < 25 x 109/L) or grade 3/4 thrombocytopenia (grade 3 platelet count: 25 x 109/L to < 50 x 109/L) associated with bleeding.

C. Complicated grade 4 neutropenia (< 0.5 x 109/L): fever, sepsis > 5 days of duration.

D. Any significant* grade 2 and higher toxicity other than nausea, vomiting, rash, alopecia or anaemia that persists longer than 35 days after the start of cycle 1.

*"Significant" defined as affecting quality of life or patient safety as determined by investigator.

Clinical and laboratory parameters will be assessed to evaluate disease response and toxicity of study therapy. Safety assessments will be performed every 3 weeks for the 18 weeks. Efficacy assessments (Radiological examination) will be performed on all patients every 9 weeks (+/- 1 week).

An End of Treatment visit will be performed for patients within 30 days (+/- 1 week) post last dose or disease progression.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Cancer Trials Ireland, Innovation House, Glasnevin, Dublin 11 Dublin 11, Ireland
  • Phone Number: +353 1 6677211
  • Email: info@cancertrials.ie

Study Locations

  • Ireland
      • Cork, Ireland
        • Cork University Hospital
      • Dublin 8, Ireland
        • St James's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Lithium, Oxaliplatin & Capecitabine
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
Dose escalation of Lithium to determine the maximum tolerated dose (MTD)
Drug: Oxaliplatin
Dose as used in standard of care - 130 mg/m2.
Drug: Capecitabine
Dose as used in standard of care - 800 - 1000 mg/m2

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of dose limiting toxicity (DLT) within the two first cycles at each dose level.
Time Frame: 26 months
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS) as defined by RECIST Criteria Version 1.1.
Time Frame: 3 years
PFS will be defined as the time from the start of treatment until disease progression or death as a result of any cause.
3 years
Objective Response Rate (ORR) as defined by RECIST Criteria Version 1.1.
Time Frame: 3 years
ORR is defined as the proportion of patients who receive a Complete Response or a Partial Response (CR + PR).
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
Safety will be assessed by standard clinical and laboratory tests.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cancer Trials Ireland

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University College Cork

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Cancer Trials Ireland Dublin 11, Ireland, Cancer Trials Ireland

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 13, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 7, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 7, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 10, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 12, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 15, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 8, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 3, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CTRIAL-IE (ICORG) 11-32
  • 2014-000186-47 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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