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Colorectal NeoplasmsPhase 1LithiumNCT03153280

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

A Phase 1 study testing Lithium, Oxaliplatin and Capecitabine in people with Colorectal Neoplasms and Stomach Neoplasm, run by Cancer Trials Ireland at 2 sites in Ireland.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Lithium, Oxaliplatin and Capecitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
2 sitesIreland
Study dates
13 Jan 2022to 7 Sep 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 13Show fewer
  • 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:
  • 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.

Who cannot join

  • 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)
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  • 2nd 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).
  • Severe chronic obstructive pulmonary disease (COPD) > Grade 2 according to NCI CTCAE v4.0.
  • Known history or family history of Brugada Syndrome.
  • Symptoms or signs of peripheral neuropathy.
  • Ongoing infection > Grade 2 according to NCI CTCAE v4.0.
  • Seizure disorder requiring medication.
  • Dehydration Grade 1 according to NCI CTCAE v4.0; patients on Low sodium diet; Addison's disease.
  • Known hypersensitivity to lithium, oxaliplatin or fluoropyrimidines.
  • Pregnant or nursing women.
  • Concurrent treatment with any other investigational agents within 30 days prior to registration.
  • 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).
  • 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).
  • Patients weighing less than 50kg.

Trial locations and contacts

2 sites in 1 country.

Ireland2 sites
  • Cork University Hospital

    Cork

  • St James's Hospital

    Dublin

Other trials in Ireland

About this study

Official 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

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.

Read the 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:

  1. Grade 3 or 4 non-haematological toxicity other than nausea, vomiting or fatigue.
  2. 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.
  3. Complicated grade 4 neutropenia (< 0.5 x 109/L): fever, sepsis > 5 days of duration.
  4. 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.

Being tested
Lithium, Oxaliplatin, Capecitabine
Medical subject headings
Colorectal Neoplasms, Stomach Neoplasms, Esophageal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LithiumDrug

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

  • OxaliplatinDrug

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

  • CapecitabineDrug

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

Study groups in NCT03153280
Study groupRoleWhat they receive
Lithium, Oxaliplatin & CapecitabineExperimentalTarget 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.
Receives: Drug: Lithium; Drug: Oxaliplatin; Drug: Capecitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 26 months

Secondary outcomes (3)
  1. Progression Free Survival (PFS) as defined by RECIST Criteria Version 1.1.

    PFS will be defined as the time from the start of treatment until disease progression or death as a result of any cause.

    Measured: 3 years

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

    ORR is defined as the proportion of patients who receive a Complete Response or a Partial Response (CR + PR).

    Measured: 3 years

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

    Safety will be assessed by standard clinical and laboratory tests.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 May 2017
  2. Study start13 Jan 2022
  3. Primary completion7 Sep 2023
  4. Study completion7 Sep 2023

Why it stopped: Poor accrual and the field has moved on.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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.
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03153280
Sponsor's protocol ID
CTRIAL-IE (ICORG) 11-32
Other IDs
2014-000186-47, 2014
Acronym
Lithium
Status last verified
Jul 2025
First submitted
10 May 2017
Last updated
8 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Lithium, Oxaliplatin and Capecitabine in people with Colorectal Neoplasms and Stomach Neoplasm, run by Cancer Trials Ireland at 2 sites in Ireland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Poor accrual and the field has moved on.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose limiting toxicity (DLT) within the two first cycles at each dose level. (time frame: 26 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2025.

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