Pilot Study of mTOR Inhibitor Therapy in Peutz-Jeghers Syndrome

NCT00811590 | Terminated Phase 2 Results DMC

• 1 other identifier: HCI26943
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Pilot study, Open-label, Phase II study of Everolimus. Objective: To determine if Everolimus can diminish large gastrointestinal polyps in patients with Peutz-Jeghers Syndrome. Methodology: Polyp size and number will be compared to baseline by FDG-PET and CT and 12 months after treatment with Everolimus. Since this is a pilot study, the polyps prior to treatment will serve as the controls.

Conditions

Peutz-Jeghers Syndrome

Keywords

Cancer; Polyps

Outcome Measures

Primary Outcomes (1)

• The Size of Intestinal Polyps

  24 months

Study Arms (1)

All patients

EXPERIMENTAL

All participants enrolled.

Drug: Everolimus

Interventions

Everolimus DRUG

Everolimus is a novel derivative of rapamycin. Everolimus has been in clinical development since 1996 as an immunosuppressant in solid organ transplantation. Since 2003, RAD001 is approved in Europe (trade name: Certican) via the Mutual Recognition Procedure (MRP) for the prevention of organ rejection in patients with renal and cardiac transplantation. Certican is also approved in Australia, South Africa, the Middle East, Central and South America, the Caribbean and some Asian countries. Everolimus is being investigated as an anticancer agent based on its potential to act * directly on the tumor cells by inhibiting tumor cell growth and proliferation * indirectly by inhibiting angiogenesis leading to reduced tumor vascularity (via potent inhibition of tumor cell VEGF production and VEGF-induced proliferation of endothelial cells.

Also known as: everolimus, Certican, Afinitor

All patients

Eligibility Criteria

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

You may qualify if:

• Yes/No (Response of "no" = patient ineligible)
• Patients who are 18 years or older with a clinical or genetic diagnosis of Peutz-Jeghers Syndrome.
• Patient has one or more intestinal polyps ≥ 5mm in maximum diameter by contrast enhanced CT scan that is not clinically indicated for removal or is beyond the reach of a push endoscope.
• Minimum of two weeks since any major surgery.
• Patient has had colonoscopy within the past 24 months and did not have high-grade dysplasia or colorectal cancers.
• WHO performance status £ 2
• Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hgb \> 9 g/dL
• Adequate liver function as shown by: serum bilirubin ≤ 1.5 x upper limit of normal (ULN), and serum transaminases activity ≤ 2.5 x ULN.
• Patients must be able to provide written informed consent.

You may not qualify if:

• Yes/No (Response of "yes" = patient ineligible)
• Prior treatment with any investigational drug within the preceding 4 weeks
• Chronic treatment with systemic steroids or another immunosuppressive agent
• Patients should not receive immunization with attenuated live vaccines during study period or within one week of study entry
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
• Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia
• Severely impaired lung function
• Uncontrolled diabetes as defined by fasting serum glucose \>1.5x ULN
• Any active (acute or chronic) or uncontrolled infection/ disorders.
• Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
• Liver disease such as cirrhosis, or severe hepatic impairment (Child-Pugh class C)
• A known history of HIV seropositivity
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)

Sponsors & Collaborators

• University of Utah: lead
• Novartis: collaborator

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Peutz-Jeghers Syndrome; Neoplasms; Polyps

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neoplastic Syndromes, Hereditary; Intestinal Polyposis; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lentigo; Melanosis; Hyperpigmentation; Pigmentation Disorders; Skin Diseases; Skin and Connective Tissue Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed

Results Point of Contact

• Title: Dr. Randall Burt
• Organization: Huntsman Cancer Institute

randall.burt@hci.utah.edu

801-585-3281

Study Officials

• Randall W Burt, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

• Scott Kuwada, MD

  University of Hawaii

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2008
• First Posted: December 19, 2008
• Study Start: November 1, 2008
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: September 19, 2024
• Results First Posted: July 4, 2012

Record last verified: 2024-08

Locations

US (1)