COLA: A Pilot Clinical Trial of COX-2 Inhibition in LAM and TSC

NCT02484664 | Completed Phase 2 Results DMC

• 1 other identifier: 2015P000954
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators will perform a two-center phase I trial of celecoxib (COX-2 inhibitor) administered at 200mg by mouth daily for 6 months. Up to 12 adult women with LAM will be recruited (between 4-8 at each site). The Specific Aims are: Aim 1: To investigate whether, in LAM patients, celecoxib is safe and well tolerated, and has evidence of clinical benefit. Aim 2: To investigate the potential value of a novel biomarker of LAM, quantitative measurement of the number of TSC2 mutant LAM cells per ml of blood, to assess disease severity.

Conditions

Lymphangioleiomyomatosis (LAM)

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability

  Number of Participants with Adverse Events as a Measure of Safety and Tolerability in LAM patients

  1 year

Secondary Outcomes (6)

• FEV1

  1 year

• Angiomyolipoma Size Measured Volumetrically on MRI

  1 year

• St. George's Respiratory Questionnaire

  1 year

• VEGF-D Serum Levels

  6 months

• EBC Prostaglandin Metabolites

  1 year

Study Arms (1)

celecoxib

EXPERIMENTAL

Celecoxib 200mg PO QD for 6 months

Drug: Celecoxib

Interventions

Celecoxib DRUG

We will perform a pilot clinical trial to investigate the safety and tolerability of celecoxib therapy as a single agent for patients with LAM. LAM subjects who are not taking everolimus or rapamycin will be treated with celecoxib at 200mg PO QD for 6 months. They will be monitored for respiratory function and angiomyolipoma size. At the end of the 6 month period, celecoxib will be discontinued, and subjects will be monitored for another 6 months.

celecoxib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female of age 18 to 69
• Ability to give informed consent
• Definite diagnosis of LAM Typical cystic change on CT scan of the chest plus one of the following i) biopsy or cytology of any tissue demonstrating LAM, ii) angiomyolipoma, chylothorax, clinical or genetic diagnosis of tuberous sclerosis, iii) serum VEGF-D \> 800pg/ml
• post-bronchodilator forced expiratory volume in one second ≥ 70% of predicted and DLCO ≥ 70% predicted during baseline visit.
• Women of childbearing potential must agree to use two forms of barrier contraception after screening visit, for the duration of study participation and for 30 days after last dose.

You may not qualify if:

• History of intolerance to non-steroidal anti-inflammatory drugs (NSAIDs)
• History of current regular use (daily most days of the week) of NSAIDs
• History of use of rapamycin or everolimus
• Uncontrolled intercurrent illness
• Pregnant, breast feeding or planning to become pregnant in the next 2 years
• Significant hematological (platelet count \<100.000/µl or hepatic abnormalities (Liver function tests \>2 times normal).
• Use of an investigational drug within 30 days of study start
• Inability to attend scheduled clinic visits
• Inability to give informed consent
• Inability to perform spirometry
• Creatinine \> 1.0 mg/dl or eGFR \< 60 ml/min
• Pneumothorax within past 8 weeks
• History of malignancy in the last 2 years other than basal cell skin cancer
• Use of estrogen containing medication within 30 days of enrolment
• Currently taking doxycycline, metformin, lupron or simvastatin

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• El-Chemaly S, Taveira-DaSilva A, Bagwe S, Klonowska K, Machado T, Lamattina AM, Goldberg HJ, Jones AM, Julien-Williams P, Maurer R, Rosas IO, Henske EP, Moss J, Kwiatkowski DJ. Celecoxib in lymphangioleiomyomatosis: results of a phase I clinical trial. Eur Respir J. 2020 May 27;55(5):1902370. doi: 10.1183/13993003.02370-2019. Print 2020 May. No abstract available.

  PMID: 32060062 DERIVED

MeSH Terms

Conditions

Lymphangioleiomyomatosis

Interventions

Celecoxib

Condition Hierarchy (Ancestors)

Lymphangiomyoma; Neoplasm, Lymphatic Tissue; Neoplasms by Histologic Type; Neoplasms; Perivascular Epithelioid Cell Neoplasms; Neoplasms, Connective and Soft Tissue; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

pilot study

Results Point of Contact

• Title: Dr. David Kwiatkowski
• Organization: Brigham and Women's Hospital

dk@rics.bwh.harvard.edu

8573070781

Study Officials

• David J Kwiatkowski, MD PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Senior Physician

Study Record Dates

• First Submitted: June 25, 2015
• First Posted: June 30, 2015
• Study Start: June 15, 2016
• Primary Completion: November 19, 2018
• Study Completion: November 19, 2018
• Last Updated: January 20, 2022
• Results First Posted: January 20, 2022

Record last verified: 2022-01

Locations

US (1)