Testicular CancerPhase 2RADITNCT01242631
Everolimus for Patients With Relapsed/Refractory Germ Cell Cancer
A Phase 2 study testing Everolimus in people with Testicular Cancer and Germ Cell Cancer, run by Hannover Medical School at 8 sites in Germany.
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). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Testicular Cancer, Germ Cell Cancer
- What is being tested?
- Everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 8 sitesGermany
- Study dates
- Nov 2010to Mar 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Germany8 sites
Vivantes Klinikum am Urban
Berlin, 10967
Universitatsklinikum Essen
Essen, 45122
Universitatsklinikum Hamburg-Eppendorf
Hamburg, 20246
Hannover Medical School
Hanover, 30625
Universitatsklinikum Schieswig-Holstein - Campus Kiel
Kiel, 24105
Universitatsklinikum Marburg
Marburg, 35043
Klinikum Harlaching München
München, 81545
Universitatsklinikum der Eberhard-Karls-Universitat Tübingen
Tübingen, 72076
About this study
Official title: A Single Arm, Open-label Multicenter Phase II Trial of Everolimus in Patients With Relapsed/Refractory Germ Cell Cancer
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.
Read the detailed 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.
- Conditions
- Testicular Cancer, Germ Cell Cancer
- Being tested
- Everolimus
- Medical subject headings
- Testicular Neoplasms, Neoplasms, Germ Cell and Embryonal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called Afinitor
Everolimus 10 mg orally per day.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus 10 mg daily | Experimental | Not described Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free rate at 12 weeks
Percentage of patients that have not progressed after 12 weeks of treatment.
Measured: 12 weeks
Secondary outcomes (3)
Objective response rate
Measured: 6 months
Overall survival
Measured: 12 months
Safety profile
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2010 (estimated)
- Study startNov 2010
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Testicular CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hannover Medical School
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Martin H Fenner, MD, Principal investigator, Hannover Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01242631
- Sponsor's protocol ID
- CRAD001CDE21T
- Other IDs
- 2009-014383-18, 2009
- Acronym
- RADIT
- Status last verified
- Feb 2015
- First submitted
- 16 Nov 2010
- Last updated
- 25 Feb 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Fenner M, Oing C, Dieing A, Gauler T, Oechsle K, Lorch A, Hentrich M, Kopp HG, Bokemeyer C, Honecker F. Everolimus in patients with multiply relapsed or cisplatin refractory germ cell tumors: results of a phase II, single-arm, open-label multicenter trial (RADIT) of the German Testicular Cancer Study Group. J Cancer Res Clin Oncol. 2019 Mar;145(3):717-723. doi: 10.1007/s00432-018-2752-z. Epub 2018 Sep 19.
PubMed 30232558
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm, Open-label Multicenter Phase II Trial of Everolimus in Patients With Relapsed/Refractory Germ Cell Cancer
- ClinicalTrials.gov ID
- NCT01242631
- Acronym / sponsor ID
- RADIT / CRAD001CDE21T
- Conditions
- Testicular Cancer, Germ Cell Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Hannover Medical SchoolUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Nov 2010
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 17 Nov 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Everolimus 10 mg daily | Experimental | Drug: Everolimus |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EverolimusAlso: AfinitorEverolimus 10 mg orally per day. | Drug | Everolimus 10 mg daily |
Primary outcome
Progression-free rate at 12 weeks
Time frame: 12 weeks
Percentage of patients that have not progressed after 12 weeks of treatment.
3 secondary outcomes
Objective response rate
Time frame: 6 months
Overall survival
Time frame: 12 months
Safety profile
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2015.
- Derived from this study: PubMed 30232558Fenner M, Oing C, Dieing A, Gauler T, Oechsle K, Lorch A, Hentrich M, Kopp HG, Bokemeyer C, Honecker F. Everolimus in patients with multiply relapsed or cisplatin refractory germ cell tumors: results of a phase II, single-arm, open-label multicenter trial (RADIT) of the German Testicular Cancer Study Group. J Cancer Res Clin Oncol. 2019 Mar;145(3):717-723. doi: 10.1007/s00432-018-2752-z. Epub 2018 Sep 19.
- Related info at sponsor clinical trial registryLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin H Fenner, MD principal investigator
Hannover Medical School
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus in people with Testicular Cancer and Germ Cell Cancer, run by Hannover Medical School at 8 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free rate at 12 weeks (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01242631, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2015.