Renal Cell CancerPhase 2NCT01246817
Temsirolimus-RCC-imaging
A Phase 2 study testing Temsirolimus in people with Renal Cell Cancer, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
This study uses one trialdrug: Temsirolimus (sometimes called Torisel ® ). Temsirolimus is an mTOR inhibitor. It is an agent that is specifically aimed at disrupting cell division (needed for cancer cell growth). Temsirolimus has been shown to inhibit the growth of cancer cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Cancer
- What is being tested?
- Temsirolimus
- Type of treatment
- Injection or infusion
- How many people
- 51 participants
- Where
- 1 siteNetherlands
- Study dates
- Aug 2009to Aug 2012
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients with histologically confirmed, advanced (stage IV or recurrent disease) RCC who have received at least one prior angiogenesis inhibitor for their disease.
- Karnofsky performance status ≥ 70.
- At least 1 measurable lesion that can be accurately measured in at least 1 dimension with the longest diameter ≥ 10-mm when measured by spiral computerized tomography (CT, 5-mm slice thickness contiguous)
- Age ≥ 18 years.
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500 cells/mm3), platelet count ≥ 100 x 109/ L (100,000 cells/ mm3), hemoglobin ≥ 8.0 g/dL (5.0 mmol/L).
- Adequate renal function (serum creatinine ≥ 1.5 times the ULN) or creatinin clearance of ≥ 50 ml/min
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- Adequate hepatic function (bilirubin ≤ 1.5 times the ULN, aspartate transaminase (AST) ≤ 3 times the ULN [≤ 5 times the ULN if liver metastases are present]).
- Fasting serum cholesterol ≤ 350 mg/dL (9.0 mmol/L), triglycerides ≤ 400 mg/dL (4.56 mmol/ L).
- Subjects receiving cytochrome P450 (CYP) 3A4 inducers or inhibitors must be on stable doses for at least 1 week prior to randomization.
- Life expectancy of at least 8 weeks.
- Negative pregnancy test for female patients of childbearing potential
- Women and men enrolled into this trial must use adequate birth control measures during the course of the trial and must continue for 3 months after the last dose of temsirolimus.
- Signed and dated written informed consent form
Who cannot join
- Subjects with central nervous system (CNS) metastases. Subjects with a prior history of CNS metastases will be eligible if the screening magnetic resonance imaging (MRI)/CT (with contrast) indicates no residual disease.
- Prior investigational therapy/agents within 2 weeks of randomization.
- Prior treatment with a mTOR inhibitor
- History of other prior malignancy in past 5 years, other than basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ.
- Not recovered from prior surgery and/or surgery or radiation therapy within 4 weeks of randomization.
- Immunocompromised subjects, including subjects known to be human immunodeficiency virus (HIV) positive, hepatitis B positive, or hepatitis C positive.
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- Active infection or serious intercurrent illness.
- Presence of unstable angina or myocardial infarction within the previous 6 months (prior to screening), use of ongoing maintenance therapy for life-threatening arrhythmia, known pulmonary hypertension, or pneumonitis.
- Pregnant or nursing women, women who are of childbearing potential who are not using an effective contraceptive method, or men with partners of childbearing potential who are not using an effective contraceptive method. (A woman of childbearing potential is defined as a woman who is biologically capable of becoming pregnant.)
- Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
University Medical Centre Nijmegen
Nijmegen, Gelderland, 6500 HB
C.M.L. van Herpen, Md PhD
About this study
Official title: Evaluation of the Activity of Temsirolimus With FDG-PET and FLT-PET in Patients With Renal Cell Cancer
This study uses one trialdrug: Temsirolimus (sometimes called Torisel ® ). Temsirolimus is an mTOR inhibitor. It is an agent that is specifically aimed at disrupting cell division (needed for cancer cell growth). Temsirolimus has been shown to inhibit the growth of cancer cells. For patients with metastatic kidney cancer Temsirolimus is now a registered , conventional therapy. It has been recorded for patients as they get renal cell cancer metastases and which looks as if the tumor is aggressive.
This is a phase II trial. This means that the investigators look at how effectively temsirolimus is, after treatment with other drugs against kidney cancer. Effective means that the investigators see how well the treatment is, the investigators look at how long the disease is not growing and if it does, that is smaller. The possible side effects will be carefully watched.
Read the detailed description
The prognosis of metastatic renal cell carcinoma (mRCC) patients has improved the last couple of years, due to the treatment with angiogenesis inhibitors and mTOR inhibitors. First line and second line therapy is nowadays standard. However, responses on third or fourth line therapy, in RCC patients participating in phase I studies have been observed. As yet the optimal sequence of therapeutic agents in mRCC is not known and data on progression free survival of third or fourth line treatment is not available. More and more patients with metastatic RCC will receive multiple sequential treatments. A large proportion of those patients will remain in a good condition and have a good quality of life. Those are the candidates for new lines of therapy.
In the evaluation of new treatments the difficulty lies in the way of assessment of activity of new drugs. In the past, chemotherapy induced real volume responses, whereas with the new targeted agents volume reponse may take a long period of time (more than 6 months is not exceptionial), or will never induce a real decrease in tumor volume, while the patient may benefit from a long period of stable disease. All these new drugs are costly and not without side effects, and therefore there is an urgent need for new end points of therapy, better reflecting the activity of the drug.
In first line poor prognosis metastatic RCC patients mTor inhibition with temsirolimus has become standard therapy based on an improvement in PFS and OS. Also for temsirolimus RECIST criteria have been used. However, by using the RECIST criteria for the evaluation of efficacy only the change in tumour volume is assessed. Temsirolimus is an antiproliferative anti cancer drug and proliferation might be assessed by FLT PET or FDG PET.
Until now only very limited data have been published on the role of FDG PET and FLT PET after mTor inhibitors. FLT PET seems promising in mice glioblastoma in mice treated with mTor inhibitors. Another very recent paper reports the value of FDG PET as suurogate marker of everolimus activity, also in mice. Only one clinical study in which FDG PET was used in patients treated with mTor inhibitors had included patients with a mixture of diagnoses.
Therefore, we propose to investigate in a systematic way whether molecular imaging with FLT-PET and/or FDGPET is a better predictor of response and progression free survival (PFS) than evaluation by standard anatomical imaging by CT-scan in RCC patients treated with temsirolimus. Furthermore, we propose to investigate the optimal way of assessment of molecular characteristics of the tumor (metabolism, proliferation) by comparing FLT-PET with FDG-PET.
- Conditions
- Renal Cell Cancer
- Being tested
- Temsirolimus
- Keywords
- Carcinoma, Renal Cell, temsirolimus, FLT-PET, FDG-PET, Adult patients with metastatic RCC (any histology and any MSKCC prognostic score), with documented, progressive disease after more than two prior systemic treatments with any of the following: cytokines (±, chemotherapy), sunitinib, sorafenib, or bevacizumab (± IFN).
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemsirolimusDrug
temsirolimus (standard schedule: 25 mg weekly, by 1-hour i.v. infusion)
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of the FLT-PET and FDG-PET
Measurement of 18F-FLT-PET-signal and FDG-PET-signal (ROI analysis and SUVmax calculation), and signal changes during treatment with temsirolimus (percentage change in SUVmax) Correlation of 18F-FLT-PET and FDG-PET before, and signal changes during treatment with treatment outcome (clinical response and PFS).
Measured: before and during treatment
Secondary outcomes (4)
Progression free survival
Assessment of duration of PFS after treatment with temsirolimus in heavily pre-treated metastatic RCC patients
Measured: after treatment
response rate
Measurement of the response rate
Measured: during the trial
Toxicity
patients are monitored during the trial for toxicities using CTC AE version 3.0. If applicable neccesary dose-adjustments will be made
Measured: during and after the trial
Correlation of pharmacodynamics with PET results
Regulatory T cells, insulin growth factor (IGF), insulin growth factor big protein-2 (IGFBP), angiogenic markers, circulating endothelial cells (CECs) and circulating tumor cells (CTCs) will be determined. The results will be correlated with the PET scanning data.
Measured: baseline, after 2nd Temsirolimus infusion after the 6th temsirolimus infusion (approx 5 days after), at time of PD and 2 weeks after the last Temsirolimus infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2010 (estimated)
- Study startAug 2009
- Primary completionAug 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Cell 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
- 51 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- C.M.L. van Herpen, Md PhD, Principal investigator, University Medical Centre Nijmegen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01246817
- Sponsor's protocol ID
- UMCNONCO200903
- Status last verified
- Apr 2012
- First submitted
- 22 Nov 2010
- Last updated
- 11 Apr 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Activity of Temsirolimus With FDG-PET and FLT-PET in Patients With Renal Cell Cancer
- ClinicalTrials.gov ID
- NCT01246817
- Acronym / sponsor ID
- UMCNONCO200903
- Conditions
- Renal Cell Cancer
- Keywords
- Carcinoma, Renal Cell, temsirolimus, FLT-PET, FDG-PET, Adult patients with metastatic RCC (any histology and any MSKCC prognostic score), with documented, progressive disease after more than two prior systemic treatments with any of the following: cytokines (±, chemotherapy), sunitinib, sorafenib, or bevacizumab (± IFN).
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 51 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Aug 2009
- Primary completion
- Aug 2012 (estimated)
- First posted
- 23 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.
This study uses one trialdrug: Temsirolimus (sometimes called Torisel ® ). Temsirolimus is an mTOR inhibitor. It is an agent that is specifically aimed at disrupting cell division (needed for cancer cell growth). Temsirolimus has been shown to inhibit the growth of cancer cells. For patients with metastatic kidney cancer Temsirolimus is now a registered , conventional therapy. It has been recorded for patients as they get renal cell cancer metastases and which looks as if the tumor is aggressive.
This is a phase II trial. This means that the investigators look at how effectively temsirolimus is, after treatment with other drugs against kidney cancer. Effective means that the investigators see how well the treatment is, the investigators look at how long the disease is not growing and if it does, that is smaller. The possible side effects will be carefully watched.
Detailed description
The prognosis of metastatic renal cell carcinoma (mRCC) patients has improved the last couple of years, due to the treatment with angiogenesis inhibitors and mTOR inhibitors. First line and second line therapy is nowadays standard. However, responses on third or fourth line therapy, in RCC patients participating in phase I studies have been observed. As yet the optimal sequence of therapeutic agents in mRCC is not known and data on progression free survival of third or fourth line treatment is not available. More and more patients with metastatic RCC will receive multiple sequential treatments. A large proportion of those patients will remain in a good condition and have a good quality of life. Those are the candidates for new lines of therapy.
In the evaluation of new treatments the difficulty lies in the way of assessment of activity of new drugs. In the past, chemotherapy induced real volume responses, whereas with the new targeted agents volume reponse may take a long period of time (more than 6 months is not exceptionial), or will never induce a real decrease in tumor volume, while the patient may benefit from a long period of stable disease. All these new drugs are costly and not without side effects, and therefore there is an urgent need for new end points of therapy, better reflecting the activity of the drug.
In first line poor prognosis metastatic RCC patients mTor inhibition with temsirolimus has become standard therapy based on an improvement in PFS and OS. Also for temsirolimus RECIST criteria have been used. However, by using the RECIST criteria for the evaluation of efficacy only the change in tumour volume is assessed. Temsirolimus is an antiproliferative anti cancer drug and proliferation might be assessed by FLT PET or FDG PET.
Until now only very limited data have been published on the role of FDG PET and FLT PET after mTor inhibitors. FLT PET seems promising in mice glioblastoma in mice treated with mTor inhibitors. Another very recent paper reports the value of FDG PET as suurogate marker of everolimus activity, also in mice. Only one clinical study in which FDG PET was used in patients treated with mTor inhibitors had included patients with a mixture of diagnoses.
Therefore, we propose to investigate in a systematic way whether molecular imaging with FLT-PET and/or FDGPET is a better predictor of response and progression free survival (PFS) than evaluation by standard anatomical imaging by CT-scan in RCC patients treated with temsirolimus. Furthermore, we propose to investigate the optimal way of assessment of molecular characteristics of the tumor (metabolism, proliferation) by comparing FLT-PET with FDG-PET.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- patients with histologically confirmed, advanced (stage IV or recurrent disease) RCC who have received at least one prior angiogenesis inhibitor for their disease.
- Karnofsky performance status ≥ 70.
- At least 1 measurable lesion that can be accurately measured in at least 1 dimension with the longest diameter ≥ 10-mm when measured by spiral computerized tomography (CT, 5-mm slice thickness contiguous)
- Age ≥ 18 years.
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500 cells/mm3), platelet count ≥ 100 x 109/ L (100,000 cells/ mm3), hemoglobin ≥ 8.0 g/dL (5.0 mmol/L).
Key exclusion criteria (10 listed)
- Subjects with central nervous system (CNS) metastases. Subjects with a prior history of CNS metastases will be eligible if the screening magnetic resonance imaging (MRI)/CT (with contrast) indicates no residual disease.
- Prior investigational therapy/agents within 2 weeks of randomization.
- Prior treatment with a mTOR inhibitor
- History of other prior malignancy in past 5 years, other than basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ.
- Not recovered from prior surgery and/or surgery or radiation therapy within 4 weeks of randomization.
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 |
|---|---|---|
| Temsirolimustemsirolimus (standard schedule: 25 mg weekly, by 1-hour i.v. infusion) | Drug | – |
Primary outcome
Evaluation of the FLT-PET and FDG-PET
Time frame: before and during treatment
Measurement of 18F-FLT-PET-signal and FDG-PET-signal (ROI analysis and SUVmax calculation), and signal changes during treatment with temsirolimus (percentage change in SUVmax) Correlation of 18F-FLT-PET and FDG-PET before, and signal changes during treatment with treatment outcome (clinical response and PFS).
4 secondary outcomes
Progression free survival
Time frame: after treatment
response rate
Time frame: during the trial
Toxicity
Time frame: during and after the trial
Correlation of pharmacodynamics with PET results
Time frame: baseline, after 2nd Temsirolimus infusion after the 6th temsirolimus infusion (approx 5 days after), at time of PD and 2 weeks after the last Temsirolimus infusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2012.
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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.
C.M.L. van Herpen, Md PhD principal investigator
University Medical Centre Nijmegen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Temsirolimus in people with Renal Cell Cancer, run by Radboud University Medical Center at 1 site in Netherlands.
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 13 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 11 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact C.M.L. van Herpen, Md PhD (+31 24 361 03 53, c.vanherpen@onco.umcn.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of the FLT-PET and FDG-PET (time frame: before and during treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Apr 2012.