Phase I Platinum Based Chemotherapy Plus Indomethacin (PIFA)

June 2, 2026 updated by: Dr. F.Y.F.L. de Vos, UMC Utrecht

Phase I Study Evaluating Indomethacin in Combination With Platinum-based Chemotherapy

Mesenchymal stem cells (MSCs) are present in the circulation of cancer patients, and are recruited to the stroma of both the primary tumor and metastasis. Recent preclinical research has shown that in response to platinum-based chemotherapy, MSCs secrete two specific platinum-induced fatty acids (PIFAs) which induce resistance to a broad spectrum of chemotherapies. The secreted PIFAs are the fatty acid oxo-heptadecatetraenoic acid (KHT) and the omega-3 fatty acid hexadecatetraenoic acid (16:4). These PIFAs are produced via the COX-1 pathway. COX inhibitors, including indomethacin. This phase 1 study explores the safety of combining indomethacin with platinum containing chemotherapy.

Study Overview

Status

Status

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

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.

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.
13

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 Locations

  • Netherlands
    • Amsterdam
      • Amsterdam, Amsterdam, Netherlands, 1066 CX
        • The Netherlands Cancer Institute
    • Utrecht
      • Amersfoort, Utrecht, Netherlands, 3813TZ
        • Meander Medisch Centrum
      • Utrecht, Utrecht, Netherlands, 3584CX
        • UMC Utrecht
  • Switzerland
      • Bellinzona, Switzerland, CH-6500
        • Oncology Institute of Southern Switzerland

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:

  • Subjects with a histological proven malignancy receiving cisplatin combined with gemcitabine or 5FU/capecitabine. (cisplatin dose range 60-80 mg/m2) (Arm I) or CAPOX (oxaliplatin, capecitabine) (Arm II) in a 21 day cycle.
  • Age ≥ 18 years
  • Platinum-based chemotherapy naïve for at least 6 months.
  • Subjects with at least one evaluable lesion.
  • WHO Performance Status of 0 or 1.
  • Female participants should be of non-child bearing potential either physiologic or by using adequate contraception, have a negative serum pregnancy test, and refrain from breast feeding.
  • Written informed consent.

Exclusion Criteria:

  • Known or suspected allergy or hypersensitivity to indomethacin or any agent given in association with this trial, in particular subjects who have a history of severe hypersensitivity reactions to anti-emetics (5-HT3 antagonists, metoclopramide or corticosteroids) and acetylsalicylic acid or other prostaglandin synthetase inhibitors.
  • Symptomatic brain or meningeal tumors
  • Subjects with seizure disorder requiring medication (such as corticosteroids or anti-epileptics).
  • Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
  • Uncontrolled high blood pressure, history of labile hypertension, or history of poor compliance with an antihypertensive regimen
  • Unstable angina pectoris
  • Symptomatic congestive heart failure NYHA class ≥ 3 (see appendix 13.6)
  • Myocardial infarction ≤ 6 months prior to randomization
  • Serious uncontrolled cardiac arrhythmia
  • Active peptic ulcer disease, gastritis, inflammatory bowel disease.
  • History of active gastrointestinal bleeding
  • History of cerebrovascular disease
  • Bleeding diathesis
  • Chronic renal disease defined as GFR (MDRD) <60 ml/min
  • Absolute Neutrophil Count (ANC) < 1.5 x 109/L (< 1500/mm3)
  • Platelets (PLT) < 100 x 109/L (< 100,000/mm3)
  • Hemoglobin (Hgb) < 6.0 mmol/l (patients may be transfused to achieve adequate Hb)
  • Partial thromboplastin time (PTT) > 1,5 x ULN
  • Serum bilirubin > 1.5 ULN
  • Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) > 3.0 x ULN (> 5 x ULN if liver metastases present)
  • Patients who are unable or unwilling to comply with the protocol
  • Chronic treatment with a corticosteroid agent (nebulized corticosteroids are allowed)
  • Patients who received radiation therapy within 4 weeks of the start of the study
  • Patients who received an experimental agent less than 4 weeks before start of the study.
  • Patients who used Omega-3/omega-6 containing products, including fish oil products less than 2 weeks before start of the study.
  • Chronic use of NSAID's and/or acetylsalicylic acid and/or other prostaglandin synthetase inhibitors.
  • Use of anticoagulant therapy

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: Other
  • Allocation: Non-Randomized
  • 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: Capecitabine/Oxaliplatin
Patients receiving Capecitabine/Oxaliplatin chemotherapy
Drug: Indomethacin
3 times per day from 2 days before until 5 days after chemotherapy. Escalating dosage each cohort.
Experimental: Cisplatin + Xeloda(Capecitabine) or Gemcitabine
Patients receiving Cisplatin regimen
Drug: Indomethacin
3 times per day from 2 days before until 5 days after chemotherapy. Escalating dosage each cohort.

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
Time Frame
Number of dose limiting toxicities at each dosage cohort
Time Frame: From first dose of indomethacin until 28 days after last dose of indomethacin
From first dose of indomethacin until 28 days after last dose of indomethacin

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
Pharmacodynamics
Time Frame: During first 2 cycles of 3 weeks each
Serum levels of mesenchymal stem cells and platinum induced fatty acids at T = pre-chemotherapy, one, two and four hours expressed in pmol/L.
During first 2 cycles of 3 weeks each
Efficacy
Time Frame: From baseline to date of progressive disease according RECIST 1.1, approximately 9 to 18 weeks
Efficacy will be assessed according RECIST 1.1 criteria. Progression free survival is defined as time from baseline CT scan to progressive disease according RECIST 1.1 criteria.
From baseline to date of progressive disease according RECIST 1.1, approximately 9 to 18 weeks

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.
UMC Utrecht

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.
  • Principal Investigator: F.Y.F.L. de Vos, MD/PhD, UMC Utrecht

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

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.
September 1, 2012

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.
August 30, 2017

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.
August 30, 2017

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).
October 30, 2012

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.
October 30, 2012

First Posted (Estimated)

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.
November 1, 2012

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.
June 4, 2026

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.
June 2, 2026

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.
June 1, 2026

More Information

Terms related to this study

Keywords

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.
  • NL40487.041.12

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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