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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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.


Detailed Summary:

Background: Lymphangioleiomyomatosis (LAM) is characterized by cystic lung destruction, kidney angiomyolipomas (AMLs), and LAM cell growth within the axial lymphatics and multiple other organs and surfaces. LAM occurs both sporadically and in association with tuberous sclerosis complex (TSC). Sirolimus (rapamycin), an mTORC1 inhibitor, has been shown to stabilize lung function decline and decrease angiomyolipoma tumor size in both TSC and sporadic LAM patients. However, cessation of rapamycin therapy results in recurrent decline in lung function, and regrowth of angiomyolipoma, suggesting that continuous use may be required to maintain its beneficial effects. Recently the investigators have discovered that cyclo-oxygenase (COX) function is altered in cells lacking TSC2, including in a LAM patient-derived angiomyolipoma cell line. COX-2 levels are increased, prostaglandin metabolite levels are increased, and treatment with COX-2 inhibitors are effective in reducing tumor size in two different Tsc mouse models, one a native tumor, and the other a xenograft model. Furthermore, rapamycin does not affect these differences in COX-2 expression or prostaglandin metabolites.

Objectives/Hypothesis: Our preclinical studies indicate that celecoxib (a COX-2 specific inhibitor) decreases the size of TSC2-deficient tumors in Tsc models. Hence the investigators propose this Pilot Clinical Trial to test the safety and tolerability of celecoxib in patients with LAM, with preliminary assessment of potential benefit using multiple approaches.

Specific aims: The primary endpoint of this pilot trial is to test the safety and tolerability of treatment with celecoxib in patients with mild-to-moderate LAM, who are not currently on sirolimus; and to assess the potential benefit of this treatment using the following: 1. Spirometry, 2. MRI me
Sponsor: Brigham and Women's Hospital

Current Primary Outcome: Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 2 years ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • FEV1 [ Time Frame: 1 year ]
  • angiomyolipoma size measured volumetrically on MRI [ Time Frame: 1 year ]
  • St. George's Respiratory Questionnaire [ Time Frame: 1 year ]
  • VEGF-D serum levels [ Time Frame: 1 year ]
  • Exhaled breath condensate prostaglandin metabolites [ Time Frame: 1 year ]
  • circulating LAM cell count [ Time Frame: 1 year ]


Original Secondary Outcome: Same as current

Information By: Brigham and Women's Hospital

Dates:
Date Received: June 25, 2015
Date Started: January 2016
Date Completion: June 2018
Last Updated: July 19, 2016
Last Verified: July 2016