Phase I Platinum Based Chemotherapy Plus Indomethacin

NCT ID: NCT01719926

Last Updated: 2017-08-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2017-08-31

Brief 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 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.

Conditions

Colorectal Neoplasms; Esophageal Neoplasms; Ovarian Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Capecitabine/Oxaliplatin

Patients receiving Capecitabine/Oxaliplatin chemotherapy

Group Type: EXPERIMENTAL

Indomethacin

Intervention Type: DRUG

3 times per day from 2 days before until 5 days after chemotherapy. Escalating dosage each cohort.

Cisplatin + Xeloda(Capecitabine) or Gemcitabine

Patients receiving Cisplatin regimen

Group Type: EXPERIMENTAL

Indomethacin

Intervention Type: DRUG

3 times per day from 2 days before until 5 days after chemotherapy. Escalating dosage each cohort.

Interventions

Indomethacin

3 times per day from 2 days before until 5 days after chemotherapy. Escalating dosage each cohort.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UMC Utrecht

OTHER

Sponsor Role: lead

Responsible Party

Dr. F.Y.F.L. de Vos

MD/PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

F.Y.F.L. de Vos, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

UMC Utrecht

Locations

Meander Medisch Centrum

Amersfoort, Utrecht, Netherlands

the Netherlands Cancer Institute

Amsterdam, , Netherlands

UMC Utrecht

Utrecht, , Netherlands

Oncology Institute of Southern Switzerland

Bellinzona, , Switzerland

Countries

Netherlands; Switzerland

Other Identifiers

NL40487.041.12

Identifier Type: -

Identifier Source: org_study_id