Clinical Trials Logo

Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT01178151
Other study ID # AMCmedonc010
Secondary ID 2010-020451-32
Status Withdrawn
Phase Phase 2
First received July 26, 2010
Last updated April 21, 2015
Start date October 2010
Est. completion date April 2015

Study information

Verified date April 2015
Source Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Contact n/a
Is FDA regulated No
Health authority Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date April 2015
Est. primary completion date April 2015
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Tow cohorts of PJS patients will be included. Cohort 1: Advanced malignancy Cohort 2: High risk polyps

General inclusion criteria:

1. Known Peutz-Jeghers disease (with LKB1 mutation)

2. No concurrent systemic anti cancer treatment

3. No prior treatment with m-TOR inhibitor

4. Prior malignancies or concurrent second malignancies are allowed

5. Prior systemic therapy is permitted with a washout time of at least 4 weeks

6. ECOG/ WHO performance 0-2

7. Age > 18 years

8. Adequate renal function (defined as creatinine < 150 µmol/L)

9. 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

10. Adequate bone marrow function (WBC > 3.0 x 10 9/L, platelets > 100 x 10 9/L)

11. 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.

12. No pregnancy or lactating and ifof childbearing potential patients must agree to use a reliable contraceptive method throughout the study

13. No serious concomitant systemic disorder that would compromise the safety of the patient,at the discretion of the investigator

14. Signed informed consent according to ICH/GCP.

15. No uncontrolled symptomatic hyperglycaemia

Specific inclusion criteria for cohort 1:

1. Cytological or histological confirmed carcinoma

2. Metastatic or non-resectable disease

3. Patients with clinically and/or radiographically documented measurable lesion according to

RECIST criteria:

1. X-ray, physical exam > 20 mm

2. Spiral CT scan > 10 mm

3. Non-spiral CT scan > 20 mm

Specific inclusion criteria for cohort 2:

1. Known high risk polyps (definition see page 19)

2. Ability to undergo endoscopies

Specific Exclusion criteria:

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

Drug:
Everolimus
10mg daily orally

Locations

Country Name City State
Netherlands Academic Medical Center Amsterdam
Netherlands Erasmus Medical Center Rotterdam

Sponsors (2)

Lead Sponsor Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) Erasmus Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 No
Secondary To determine the overall survival of PJS patients treated with everolimus for advanced malignancies The time between date of entering the study and date of death will be collected. avarage of 18 months No
Secondary To determine the time to progression of PJS patients treated with everolimus for advanced malignancies. Determined with regular radiological scans once every 9 weeks and measured following RECIST 1.1 During treatment, expected avarage of 12 months No
Secondary To determine the safety and toxicity of Everolimus in this patient population Number of Participants with Adverse Events determined by the CTCAE 4.0 as a Measure of Safety and Tolerability During treatment, expected avarage of 12 months Yes
Secondary To determine if there is an association between measured drug blood levels and treatment outcome measured as response to treatment determined by RECIST Drug trough levels will be taken once every 3 weeks and stored frozen until measurement at the end of the study During treatment, expected avarage of 12 months No
Secondary 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. All patients who are willing to undergo extra tissue collection will have a tumor and where possible a polyp biopsy before treatment and for tumor biopsy in week 2 and 4 and for polyps once every 6 months during treatment for biomarker investigations. The activity of mTOR and its downstream targets will be measured in the tumor as well as the arborization pattern and apoptosis activity in the polyps. During treatment, expected avarage of 12 months No
See also
  Status Clinical Trial Phase
Withdrawn NCT06057636 - Hypnosis for Pain in Black Women With Advanced Breast Cancer: A Feasibility Study N/A
Terminated NCT03166631 - A Trial to Find the Safe Dose for BI 891065 Alone and in Combination With BI 754091 in Patients With Incurable Tumours or Tumours That Have Spread Phase 1
Terminated NCT01441115 - ECI301 and Radiation for Advanced or Metastatic Cancer Phase 1
Active, not recruiting NCT03775980 - CIRSE Emprint Microwave Ablation Registry
Completed NCT01114958 - Pilot Study of Intra-Arterial Cisplatin With IV Thiosulfate in Patients With Lung Cancer or Lung Metastases Phase 1
Terminated NCT03986593 - Cryoablation of Bone Metastases From Endocrine Tumors N/A
Active, not recruiting NCT04458259 - Study of PF-07265807 in Participants With Metastatic Solid Tumors. Phase 1
Completed NCT01218542 - Whole Brain Radiation Therapy With Boost to Metastatic Tumor Volume Using RapidArc N/A
Not yet recruiting NCT03175146 - A Study to See Whether Stereotactic Body RadioTherapy (SBRT) Can Shrink Tumours Within the Liver Safely N/A
Active, not recruiting NCT02395224 - A Longitudinal Study of Colorectal Cancer Patients With Metastatic Disease in Middle-Norway
Completed NCT02374411 - Knowledge, Attitudes, and Practice of Surgeons Toward Nutrition Support in HIPEC Patients N/A
Recruiting NCT01960829 - Everolimus in Selected Patients With Metastatic Melanoma: Efficacy and Safety Study Phase 2
Completed NCT01933789 - Improving Communication About Serious Illness N/A
Terminated NCT01846429 - Oral Bicarbonate as Adjuvant for Pain Reduction in Patients With Tumor Related Pain Phase 1
Recruiting NCT01564810 - Cetuximab in Combination With Chemotherapy for the Treatment of Metastatic Colorectal Cancer Phase 4
Completed NCT00375245 - Rapamycin With Grapefruit Juice for Advanced Malignancies Phase 1
Completed NCT00207116 - An Exploratory Pharmacogenomic Study of Monotherapy Erbitux in Subjects With Metastatic Non Small Cell Lung Carcinoma Phase 1
Completed NCT00232726 - Clinical Study of Previously Untreated Patients With Malignant Melanoma Phase 2
Completed NCT00172003 - Effect of Zoledronic Acid in Patients With Renal Cell Cancer and Bone Metastasis Phase 4
Completed NCT00207103 - MAD in Cancer Patients: Safety of BMS-582664 in Patients With Advanced or Metastatic Solid Tumors Phase 1