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

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • 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

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
Intervention / Treatment
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

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

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

UMC Utrecht

Investigators

  • 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

September 1, 2012

Primary Completion (Actual)

August 30, 2017

Study Completion (Actual)

August 30, 2017

Study Registration Dates

First Submitted

October 30, 2012

First Submitted That Met QC Criteria

October 30, 2012

First Posted (Estimated)

November 1, 2012

Study Record Updates

Last Update Posted (Actual)

June 4, 2026

Last Update Submitted That Met QC Criteria

June 2, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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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