The Tolerability of Saracatinib in Subjects With Lymphangioleiomyomatosis (LAM) (SLAM-1)

NCT02116712 | Completed Phase 1 DMC

• 1 other identifier: SLAM 7601
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 3

Brief Summary

Lymphangioleiomyomatosis (LAM) is a rare lung disease that mostly affects women of childbearing age. In LAM, abnormal, muscle-like cells begin to grow out of control in the lungs. As a result, air can't move freely in and out of the lungs. In some cases, this means the lungs can't supply the body's other organs with enough oxygen. This study is being conducted to find out what dose of a drug called saracatinib is best tolerated by people with LAM. This drug has been tested in patients with certain types of cancer but is not currently approved by the United States Food and Drug Administration (FDA). Saracatinib may work in cancer by preventing the growth, movement and invasiveness of cancer cells. The use of saracatinib to treat LAM is considered experimental. Preliminary testing already completed suggests that the study drug, saracatinib, may suppress certain substances in the lungs of patients with LAM thus may be effective in slowing down the disease process

Conditions

Pulmonary Lymphangioleiomyomatosis

Keywords

LAM; saracatinib; Lymphangioleiomyomatosis

Outcome Measures

Primary Outcomes (1)

• Dose Determination

  One of three escalating daily oral doses of saracatinib; 50, 125 and 175 mg. Saracatinib will be given orally once a day for four weeks. Adverse events will be monitored. The subject will receive only one of the doses as determined by the escalation of the study.

  Saracatinib will be given for 4 weeks, the subject will be followed for a total of 8 weeks.

Secondary Outcomes (1)

• Safety Profile

  8 weeks

Other Outcomes (1)

• Efficacy exploration

  8 weeks

Study Arms (1)

Saracatinib

EXPERIMENTAL

Only one arm: Intervention is Saracatinib. We plan to study three escalating doses of oral saracatinib; 50, 125 and 175 mg. Saracatinib is given orally once a day. More regarding dose escalation is included in intervention below.

Drug: Saracatinib

Interventions

Saracatinib DRUG

Saracatinib is escalated as follows: Three dose levels will be administered for 1 month each: 50 mg, 125 mg and 175 mg. Three subjects will be treated at the lowest daily dose of 50 mg. If no subject experiences DLT (dose limiting toxicity), the dose level is escalated to 125 mg/day for the next cohort of 3 different subjects and so on to next dose.

Also known as: AZD0530

Saracatinib

Eligibility Criteria

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

You may qualify if:

• Male or female patients. It should be noted, however, that LAM occurs predominantly in women.
• to 65 years of age.
• All patients must have a diagnosis of LAM as defined by one of the following:
• Open lung, transbronchial or thoracic needle biopsy consistent with LAM Open or needle abdominal biopsy findings consistent with LAM Computed tomography (CT) of chest or abdomen consistent with LAM in the setting of TSC, renal angiomyolipoma (AML), cystic abdominal lymphangiomas, or history of chylous effusion in the chest or abdomen CT of chest consistent with LAM plus serum vascular endothelial growth factor (VEGF-D) \> 800 pg/ml In cases where the diagnosis of LAM is based on biopsy, review of the pathology specimens by pathologists who are experienced with LAM, such as those at the NIH or the Mayo Clinic, will be obtained (if not done so previously).

You may not qualify if:

• Current infection.
• Major surgery within the past 2 months
• Advanced hematologic, renal, hepatic, or metabolic diseases
• The use of another investigational drug within 30 days
• The use of mammalian target of rapamycin (mTOR) inhibitors within 30 days
• Previous lung transplantation or active on transplant list.
• Inability to attend scheduled clinic visits
• Inability to give informed consent
• Inability to perform pulmonary function testing
• History of malignancy in the past two years, other than squamous or basal cell skin cancer or mild cervical cancer.
• Nursing mothers
• Current or planned pregnancy.
• Not using adequate contraception (in woman of childbearing potential).
• Significant clinical change in health in the past 30 days

Sponsors & Collaborators

• Tony Eissa: lead
• University of Texas: collaborator
• University of Cincinnati: collaborator

Study Sites (3)

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center-Houston

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lymphangioleiomyomatosis

Interventions

saracatinib

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

Study Officials

• Tony Eissa, MD

  Baylor College of Medicine

  STUDY CHAIR

• Nicola A Hanania, MD

  Baylor College of Medicine - Ben Taub Hospital

  PRINCIPAL INVESTIGATOR

• Khalid Almoosa, MD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

• Frank McCormack, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine - Pulmonary

Study Record Dates

• First Submitted: April 15, 2014
• First Posted: April 17, 2014
• Study Start: August 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: July 1, 2015
• Last Updated: November 30, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)