Study of Everolimus in the Treatment of Advanced Malignancies in Patients With Peutz-Jeghers Syndrome

NCT01178151 | Withdrawn Phase 2 DMC

• 2 other identifiers: AMCmedonc0102010-020451-32
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

In this pilot study the investigators will treat all patients known with Peutz-Jeghers syndrome (PJS) who are diagnosed with advanced malignancies with everolimus 10mg daily until disease progression. Most patients with PJS have an inherited LKB1 mutation leading to aberrant m-TOR activity. Their risk to develop malignancies or intestinal polyps is probably related to this constitutive mTOR signaling. The hypothesis is that mTOR inhibition is an effective anticancer treatment in PJS patients with advanced malignancies.

Conditions

Peutz-Jeghers Syndrome; Neoplastic Processes; Neoplasm Metastasis

Keywords

Peutz-Jeghers syndrome; mTOR inhibition; cancer

Outcome Measures

Primary Outcomes (1)

• To determine the response rate of Everolimus in patients with advanced cancer and PJS.

  Determined with regular radiological scans once every 9 weeks and measured following RECIST 1.1

  During treatment, expected avarage of 12 months

Secondary Outcomes (5)

• To determine the overall survival of PJS patients treated with everolimus for advanced malignancies

  avarage of 18 months

• To determine the time to progression of PJS patients treated with everolimus for advanced malignancies.

  During treatment, expected avarage of 12 months

• To determine the safety and toxicity of Everolimus in this patient population

  During treatment, expected avarage of 12 months

• To determine if there is an association between measured drug blood levels and treatment outcome measured as response to treatment determined by RECIST

  During treatment, expected avarage of 12 months

• To assess markers for activated mTOR pathway (including phospho-S6 and phospho-4E BP1) in all pre-treatment tissue specimens and collected specimens during treatment and correlate with response to treatment.

  During treatment, expected avarage of 12 months

Study Arms (1)

afinitor

EXPERIMENTAL

10mg afinitor daily orally

Drug: Everolimus

Interventions

Everolimus DRUG

10mg daily orally

Also known as: Afinitor, RAD001, everolimus

afinitor

Eligibility Criteria

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

You may qualify if:

• Known Peutz-Jeghers disease (with LKB1 mutation)
• No concurrent systemic anti cancer treatment
• No prior treatment with m-TOR inhibitor
• Prior malignancies or concurrent second malignancies are allowed
• Prior systemic therapy is permitted with a washout time of at least 4 weeks
• ECOG/ WHO performance 0-2
• Age \> 18 years
• Adequate renal function (defined as creatinine \< 150 μmol/L)
• Adequate liver function (bilirubin \< 1.5 times upper limit of normal, ALAT or ASAT \< 5.0 times upper limit of normal in case of liver metastases and \< 2.5 the upper limit of normal in absence of liver metastases
• Adequate bone marrow function (WBC \> 3.0 x 10 9/L, platelets \> 100 x 10 9/L)
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
• No pregnancy or lactating and ifof childbearing potential patients must agree to use a reliable contraceptive method throughout the study
• No serious concomitant systemic disorder that would compromise the safety of the patient,at the discretion of the investigator
• Signed informed consent according to ICH/GCP.
• No uncontrolled symptomatic hyperglycaemia

You may not qualify if:

• Symptomatic PJ-polyps, defined as polyps likely to be responsible/causal for the abdominal symptoms the patient presents with.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Erasmus Medical Center: collaborator

Study Sites (2)

Academic Medical Center

Amsterdam, 1105AZ, Netherlands

Location

Erasmus Medical Center

Rotterdam, 3000 CA, Netherlands

Location

Related Publications (1)

• de Brabander J, Eskens FALM, Korsse SE, Dekker E, Dewint P, van Leerdam ME, van Eeden S, Klumpen HJ. Chemoprevention in Patients with Peutz-Jeghers Syndrome: Lessons Learned. Oncologist. 2018 Apr;23(4):399-e33. doi: 10.1634/theoncologist.2017-0682. Epub 2018 Jan 25.

  PMID: 29371475 DERIVED

MeSH Terms

Conditions

Peutz-Jeghers Syndrome; Neoplastic Processes; Neoplasm Metastasis; Neoplasms

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; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Heinz-Josef Klumpen, MD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

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: MD

Study Record Dates

• First Submitted: July 26, 2010
• First Posted: August 10, 2010
• Study Start: October 1, 2010
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: April 22, 2015

Record last verified: 2015-04

Locations

NL (2)