Colorectal NeoplasmsPhase 1PIFANCT01719926
Phase I Platinum Based Chemotherapy Plus Indomethacin
A Phase 1 study testing Indomethacin in people with Colorectal Neoplasms and Esophageal Neoplasms, run by UMC Utrecht at 4 sites in 2 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasms, Esophageal Neoplasms, Ovarian Neoplasms
- What is being tested?
- Indomethacin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Sep 2012to 30 Aug 2017
- 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
- 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.
Who cannot join
- 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
Show all 27Show fewer
- 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
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Netherlands3 sites
Meander Medisch Centrum
Amersfoort, Utrecht, 3813TZ
the Netherlands Cancer Institute
Amsterdam, Amsterdam, 1066 CX
UMC Utrecht
Utrecht, Utrecht, 3584CX
Switzerland1 site
Oncology Institute of Southern Switzerland
Bellinzona, CH-6500
About this study
Official title: 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.
- Being tested
- Indomethacin
- Keywords
- Colorectal, Esophageal, Indomethacin, PIFA
- Medical subject headings
- Colorectal Neoplasms, Esophageal Neoplasms, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IndomethacinDrug
3 times per day from 2 days before until 5 days after chemotherapy. Escalating dosage each cohort.
| Study group | Role | What they receive |
|---|---|---|
| Capecitabine/Oxaliplatin | Experimental | Patients receiving Capecitabine/Oxaliplatin chemotherapy Receives: Drug: Indomethacin |
| Cisplatin + Xeloda(Capecitabine) or Gemcitabine | Experimental | Patients receiving Cisplatin regimen Receives: Drug: Indomethacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of dose limiting toxicities at each dosage cohort
Measured: From first dose of indomethacin until 28 days after last dose of indomethacin
Secondary outcomes (2)
Pharmacodynamics
Serum levels of mesenchymal stem cells and platinum induced fatty acids at T = pre-chemotherapy, one, two and four hours expressed in pmol/L.
Measured: During first 2 cycles of 3 weeks each
Efficacy
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.
Measured: From baseline to date of progressive disease according RECIST 1.1, approximately 9 to 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2012 (estimated)
- Study startSep 2012
- Primary completion30 Aug 2017
- Study completion30 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. F.Y.F.L. de Vos, UMC Utrecht
- Investigators
- F.Y.F.L. de Vos, MD/PhD, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01719926
- Sponsor's protocol ID
- NL40487.041.12
- Acronym
- PIFA
- Status last verified
- Jun 2026
- First submitted
- 30 Oct 2012
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study Evaluating Indomethacin in Combination With Platinum-based Chemotherapy
- ClinicalTrials.gov ID
- NCT01719926
- Acronym / sponsor ID
- PIFA / NL40487.041.12
- Keywords
- Colorectal, Esophageal, Indomethacin, PIFA
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Study start
- Sep 2012
- Primary completion
- 30 Aug 2017 (actual)
- Study completion
- 30 Aug 2017 (actual)
- First posted
- 1 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Capecitabine/Oxaliplatin | Experimental | Drug: IndomethacinPatients receiving Capecitabine/Oxaliplatin chemotherapy |
| Cisplatin + Xeloda(Capecitabine) or Gemcitabine | Experimental | Drug: IndomethacinPatients receiving Cisplatin regimen |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Indomethacin3 times per day from 2 days before until 5 days after chemotherapy. Escalating dosage each cohort. | Drug | Capecitabine/Oxaliplatin, Cisplatin + Xeloda(Capecitabine) or Gemcitabine |
Primary outcome
Number of dose limiting toxicities at each dosage cohort
Time frame: From first dose of indomethacin until 28 days after last dose of indomethacin
2 secondary outcomes
Pharmacodynamics
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
F.Y.F.L. de Vos, MD/PhD principal investigator
UMC Utrecht
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Indomethacin in people with Colorectal Neoplasms and Esophageal Neoplasms, run by UMC Utrecht at 4 sites in 2 countries.
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 7 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: finished, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands, Switzerland. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of dose limiting toxicities at each dosage cohort (time frame: From first dose of indomethacin until 28 days after last dose of indomethacin). 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 4 Jun 2026.