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Evaluation of the Activity of Temsirolimus With FDG-PET and FLT-PET in Patients With Renal Cell Cancer

Phase 2
18 Years
Open (Enrolling)
Renal Cell Cancer

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Trial Information

Evaluation of the Activity of Temsirolimus With FDG-PET and FLT-PET in Patients With Renal Cell Cancer

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

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

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

Type of Study:


Study Design:

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

Outcome Measure:

Evaluation of the FLT-PET and FDG-PET

Outcome Description:

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).

Outcome Time Frame:

before and during treatment

Safety Issue:


Principal Investigator

C.M.L. van Herpen, Md PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Medical Centre Nijmegen


Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Study ID:




Start Date:

August 2009

Completion Date:

Related Keywords:

  • Renal Cell Cancer
  • Carcinoma, Renal Cell
  • temsirolimus
  • 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).
  • Carcinoma, Renal Cell