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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01246817
Recruitment Status : Unknown
Verified April 2012 by Radboud University.
Recruitment status was:  Recruiting
First Posted : November 23, 2010
Last Update Posted : April 11, 2012
Information provided by (Responsible Party):
Radboud University

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Renal Cell Cancer Drug: Temsirolimus Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 51 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of the Activity of Temsirolimus With FDG-PET and FLT-PET in Patients With Renal Cell Cancer
Study Start Date : August 2009
Estimated Primary Completion Date : August 2012

Resource links provided by the National Library of Medicine

Intervention Details:
  • Drug: Temsirolimus
    temsirolimus (standard schedule: 25 mg weekly, by 1-hour i.v. infusion)

Primary Outcome Measures :
  1. 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).

Secondary Outcome Measures :
  1. Progression free survival [ Time Frame: after treatment ]
    Assessment of duration of PFS after treatment with temsirolimus in heavily pre-treated metastatic RCC patients

  2. response rate [ Time Frame: during the trial ]
    Measurement of the response rate

  3. Toxicity [ Time Frame: during and after the trial ]
    patients are monitored during the trial for toxicities using CTC AE version 3.0. If applicable neccesary dose-adjustments will be made

  4. 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 ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. patients with histologically confirmed, advanced (stage IV or recurrent disease) RCC who have received at least one prior angiogenesis inhibitor for their disease.
  2. Karnofsky performance status ≥ 70.
  3. 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)
  4. Age ≥ 18 years.
  5. 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).
  6. Adequate renal function (serum creatinine ≥ 1.5 times the ULN) or creatinin clearance of ≥ 50 ml/min
  7. 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]).
  8. Fasting serum cholesterol ≤ 350 mg/dL (9.0 mmol/L), triglycerides ≤ 400 mg/dL (4.56 mmol/ L).
  9. Subjects receiving cytochrome P450 (CYP) 3A4 inducers or inhibitors must be on stable doses for at least 1 week prior to randomization.
  10. Life expectancy of at least 8 weeks.
  11. Negative pregnancy test for female patients of childbearing potential
  12. 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.
  13. Signed and dated written informed consent form

Exclusion Criteria:

  1. 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.
  2. Prior investigational therapy/agents within 2 weeks of randomization.
  3. Prior treatment with a mTOR inhibitor
  4. 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.
  5. Not recovered from prior surgery and/or surgery or radiation therapy within 4 weeks of randomization.
  6. Immunocompromised subjects, including subjects known to be human immunodeficiency virus (HIV) positive, hepatitis B positive, or hepatitis C positive.
  7. Active infection or serious intercurrent illness.
  8. 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.
  9. 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.)
  10. Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01246817

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Contact: C.M.L. van Herpen, Md PhD +31 24 361 03 53

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University Medical Centre Nijmegen Recruiting
Nijmegen, Gelderland, Netherlands, 6500 HB
Principal Investigator: C.M.L. van Herpen, Md PhD         
Sponsors and Collaborators
Radboud University
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Principal Investigator: C.M.L. van Herpen, Md PhD University Medical Centre Nijmegen
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Responsible Party: Radboud University Identifier: NCT01246817    
Other Study ID Numbers: UMCNONCO200903
First Posted: November 23, 2010    Key Record Dates
Last Update Posted: April 11, 2012
Last Verified: April 2012
Keywords provided by Radboud University:
Carcinoma, Renal Cell
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).
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs