Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01242631
Other study ID # CRAD001CDE21T
Secondary ID 2009-014383-18
Status Completed
Phase Phase 2
First received November 16, 2010
Last updated February 24, 2015
Start date November 2010
Est. completion date March 2014

Study information

Verified date February 2015
Source Hannover Medical School
Contact n/a
Is FDA regulated No
Health authority Germany: Federal Institute for Drugs and Medical Devices
Study type Interventional

Clinical Trial Summary

The purpose of this study is to determine whether the drug everolimus is effective in the treatment of patients with relapsed cancer of the testis. This is a phase II study where all patients will receive the study drug (everolimus 10 mg daily). The primary endpoint of the study is the rate of patients that have no progressive disease after 12 weeks of treatment. Twenty-five evaluable patients will be treated in this study.


Description:

Rationale

Patients with metastatic germ cell cancer and relapse after two or more courses of cisplatin-based chemotherapy or after high-dose chemotherapy have a poor prognosis and few treatment options. Everolimus is a derivative of rapamycin and acts as a signal transduction inhibitor. Its target is mTOR (mammalian target of rapamycin), a key protein kinase regulating cell growth, proliferation and survival. The mTOR pathway activity is modulated by the PI3K1AKT pathway and is known to be deregulated in numerous human cancers, including germ cell tumors. Everolimus is being investigated as an anticancer agent based on its potential to act:

- Directly on tumor cells by inhibiting tumor cell growth and proliferation

- Indirectly by inhibiting angiogenesis leading to reduced tumor vascularity

Study design

An open-label, single arm, non-randomized, single stage phase II study. Screening phase: Baseline evaluations will be performed within 2 weeks before the first dose of study drug. Treatment phase: All patients will receive everolimus until disease progression (by RECIST or tumor markers) or unacceptable toxicity or study discontinuation for other reasons. A treatment cycle consists of 3 weeks. Dose reductions and dose interruptions (for up to 2 weeks) are allowed for intolerable toxicity. Follow-up phase: All patients will be followed for survival.

Visit schedule

Tumor Response and progression will be assessed using the RECIST criteria and assessments with tumor markers. Tumor measurements by a CT scan or MRI will be performed at screening within 2 weeks prior to the first dose of study drug. During the study period, the CT scan/MRI will be performed every 6 weeks (± one week), and at the time of discontinuation of study drug (within 2 weeks). The same type of scan (CT or MRI) used at screening must be used for all subsequent follow-up assessments. A partial or a complete response warrants a confirmation no sooner than 4 weeks and no later than 6 weeks after its observation.

Tumor markers (AFP, HCG) will be assessed every 3 weeks. A tumor marker reduction > 90% without an increase in tumor size is considered a partial response. A tumor marker increase > 25% without an increase in tumor size is considered progressive disease when confirmed 3 weeks after its observation.

Translational research

The following retrospective pathological examinations of tumor samples will be performed in those patients that gave additional informed consent:

- immunohistochemistry for the mismatch repair genes hMLH1, hMSH2, hMSH6, and PMS2, and the cell signalling effectors pMAPK, pAKT, pS6K and PTEN.

- mutation analysis for PTEN, BRAF, p53, and examination of microsatellite instability This information will be correlated with treatment response (CR, PR, SO or PD) at week 12 in an exploratory analysis.


Recruitment information / eligibility

Status Completed
Enrollment 25
Est. completion date March 2014
Est. primary completion date March 2014
Accepts healthy volunteers No
Gender Male
Age group 18 Years and older
Eligibility Inclusion Criteria:

- Male patients >= 18 years old.

- Patients with histologically proven seminomatous or non-seminomatous germ cell cancer

- Disease progression during cisplatin-based chemotherapy or

- Disease progression or relapse after high-dose chemotherapy or

- Disease progression or relapse after at least 2 different cisplatin-based regimens and contraindications for high-dose chemotherapy.

- Patients must have received prior combination chemotherapy with gemcitabine, oxaliplatin and paclitaxel (GOP). Prior treatment with a combination of two of these drugs is allowed in case of contraindications for GOP.

- Disease progression at study entry: progressive disease according to RECIST criteria in baseline examinations or tumor marker increase > 25% within 4 weeks before study entry.

- ECOG performance status <= 2.

- Life expectancy >= 3 months.

- Adequate bone marrow function: absolute neutrophil count >= 1.5 x 109/1, platelets >= 75 x 109/1, hemoglobin >= 9 g/dl.

- Adequate liver function: serum bilirubin: <= 1.5x ULN, ALT and AST <= 2.5x ULN. For patients with known liver metastases: AST and ALT <= 5x ULN.

- Adequate renal function: serum creatinine <= 2.0x ULN.

- Patients must be surgically sterile or must agree to use effective contraception during study treatment.

- Signed written informed consent.

Exclusion Criteria:

- Systemic antitumor treatment within 21 days before study entry.

- Simultaneous radiotherapy of the only target lesion(s).

- Patients who have undergone major surgery within 4 weeks prior to starting study drug (e.g. intra-thoracic, intra-abdominal, or intra-pelvic) or significant traumatic injury, or who have not recovered from the side effects of any of the above

- Patients who have previously received mTOR inhibitors (sirolimus, temsirolimus, everolimus).

- Patients receiving chronic systemic treatment with corticosteroids (dose of >= 20 mg/day methylprednisone equivalent) or another immunosuppressive agent.

- Patients with unstable angina pectoris, myocardial infarction <= 6 months prior to first study treatment, congestive heart failure NYHA III-IV or serious uncontrolled cardiac arrhythmias.

- Patients with severely impaired lung function: spirometry or DLCO < 50% of the normal predicted value.

- Uncontrolled diabetes: fasting serum glucose > 2.0x ULN.

- Patients with an active or uncontrolled infection, incl. chronic Hepatitis B or C

- Patients who have a history of another primary malignancy and are off treatment for <= 3 years, with the exception of non-melanoma skin cancer.

- Patients who have participated in another clinical trial within 30 days before study entry.

- Other serious medical conditions that could impair the ability of the patient to participate in the study.

- Patients unwilling or unable to comply with the protocol.

Study Design

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


Related Conditions & MeSH terms


Intervention

Drug:
Everolimus
Everolimus 10 mg orally per day.

Locations

Country Name City State
Germany Vivantes Klinikum am Urban Berlin
Germany Universitatsklinikum Essen Essen
Germany Universitatsklinikum Hamburg-Eppendorf Hamburg
Germany Hannover Medical School Hannover
Germany Universitatsklinikum Schieswig-Holstein - Campus Kiel Kiel
Germany Universitatsklinikum Marburg Marburg
Germany Klinikum Harlaching München München
Germany Universitatsklinikum der Eberhard-Karls-Universitat Tübingen Tübingen

Sponsors (2)

Lead Sponsor Collaborator
Hannover Medical School Novartis

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary Progression-free rate at 12 weeks Percentage of patients that have not progressed after 12 weeks of treatment. 12 weeks No
Secondary Objective response rate 6 months No
Secondary Overall survival 12 months No
Secondary Safety profile 6 months Yes
See also
  Status Clinical Trial Phase
Recruiting NCT00772694 - Sorafenib Monotherapy in Inoperable/Recurrent Germ Cell Carcinoma Refractory to Chemotherapy Phase 2
Completed NCT00705094 - Cardiac Function and Cardiovascular Risk Profile in Testicular Cancer Patients N/A
Terminated NCT00531687 - Trial of Paclitaxel, Gemcitabine and Cisplatin in Patients With Relapsing Germ Cell Cancer Phase 2
Terminated NCT00820287 - Identification of Predictive Markers for Testis Cancer in a Population of Men With High Risk N/A
Completed NCT00216801 - Relationship of Ochratoxin A to Upper Urologic Cancers N/A
Active, not recruiting NCT03142802 - Low-Dose CT - Stage I Testicular Cancer N/A
Recruiting NCT03232541 - The Effects of Acupuncture and the Therapist´s Communication on Chemotherapy Induced Nausea and Vomiting N/A
Completed NCT03557177 - Clinical Characterisation of the Vascular Effects of Cis-platinum Based Chemotherapy in Patients With Testicular Cancer
Active, not recruiting NCT01783145 - Shared Care Follow-up After Chemotherapy for Testicular Cancer
Recruiting NCT05611307 - Late Subclinical Cardiovascular Disease in Testicular Cancer Survivors
Completed NCT02573584 - Vascular Fingerprint Validation Study
Recruiting NCT05670938 - Follow-up After Surgery for Testicular Cancer
Recruiting NCT02994758 - Development of Diagnostics and Treatment of Urological Cancers N/A
Completed NCT02991209 - Study of Testosterone vs Placebo in Testicular Cancer Survivors Phase 2/Phase 3
Completed NCT02602041 - Knowledge and Attitudes Regarding Healthy Lifestyle and Health Behavior Change in Cancer Patients and Their Partners; A Pilot Study
Completed NCT02092740 - REtrospective Study of TESTIcular CAncer Patients at the University Magdeburg N/A
Completed NCT01482741 - Understanding Patient Perspectives on the Risks of Ionizing Radiation Used for Medical Imaging N/A
Active, not recruiting NCT01242072 - Intravenous Palifosfamide-tris in Combination With Etoposide and Carboplatin in Patients With Malignancies Phase 1
Completed NCT01135849 - B-Receptor Signaling in Cardiomyopathy N/A
Completed NCT00183820 - Study of Gemcitabine, Oxaliplatin, and Paclitaxel in Patients With Refractory Germ Cell Carcinoma Phase 2