Phase I Platinum Based Chemotherapy Plus Indomethacin

NCT01719926 | Completed Phase 1

• 1 other identifier: NL40487.041.12
• Study Type: interventional
• Target: 13
• Locations: 2 countries
• Sites: 4

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

Keywords

Colorectal; Esophageal; Indomethacin; PIFA

Outcome Measures

Primary Outcomes (1)

• Number of dose limiting toxicities at each dosage cohort

  From first dose of indomethacin until 28 days after last dose of indomethacin

Secondary Outcomes (2)

• Pharmacodynamics

  During first 2 cycles of 3 weeks each

• Efficacy

  From baseline to date of progressive disease according RECIST 1.1, approximately 9 to 18 weeks

Study Arms (2)

Capecitabine/Oxaliplatin

EXPERIMENTAL

Patients receiving Capecitabine/Oxaliplatin chemotherapy

Drug: Indomethacin

Cisplatin + Xeloda(Capecitabine) or Gemcitabine

EXPERIMENTAL

Patients receiving Cisplatin regimen

Drug: Indomethacin

Interventions

Indomethacin DRUG

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

Capecitabine/Oxaliplatin; Cisplatin + Xeloda(Capecitabine) or Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• UMC Utrecht: lead

Study Sites (4)

Meander Medisch Centrum

Amersfoort, Utrecht, 3813TZ, Netherlands

Location

the Netherlands Cancer Institute

Amsterdam, 1066 CX, Netherlands

Location

UMC Utrecht

Utrecht, 3584CX, Netherlands

Location

Oncology Institute of Southern Switzerland

Bellinzona, CH-6500, Switzerland

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Esophageal Neoplasms; Ovarian Neoplasms

Interventions

Indomethacin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• F.Y.F.L. de Vos, MD/PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD/PhD

Study Record Dates

• First Submitted: October 30, 2012
• First Posted: November 1, 2012
• Study Start: September 1, 2012
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: August 18, 2017

Record last verified: 2017-08

Locations

NL (3); CH (1)