Temsirolimus-RCC-imaging

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2012 by Radboud University.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01246817
First received: November 22, 2010
Last updated: April 10, 2012
Last verified: April 2012
  Purpose

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 Intervention Phase
Renal Cell Cancer
Drug: Temsirolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Evaluation of the FLT-PET and FDG-PET [ Time Frame: before and during treatment ] [ Designated as safety issue: No ]
    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:
  • Progression free survival [ Time Frame: after treatment ] [ Designated as safety issue: No ]
    Assessment of duration of PFS after treatment with temsirolimus in heavily pre-treated metastatic RCC patients

  • response rate [ Time Frame: during the trial ] [ Designated as safety issue: No ]
    Measurement of the response rate

  • Toxicity [ Time Frame: during and after the trial ] [ Designated as safety issue: No ]
    patients are monitored during the trial for toxicities using CTC AE version 3.0. If applicable neccesary dose-adjustments will be made

  • 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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 51
Study Start Date: August 2009
Estimated Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Temsirolimus
    temsirolimus (standard schedule: 25 mg weekly, by 1-hour i.v. infusion)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01246817

Contacts
Contact: C.M.L. van Herpen, Md PhD +31 24 361 03 53 c.vanherpen@onco.umcn.nl

Locations
Netherlands
University Medical Centre Nijmegen Recruiting
Nijmegen, Gelderland, Netherlands, 6500 HB
Principal Investigator: C.M.L. van Herpen, Md PhD         
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: C.M.L. van Herpen, Md PhD University Medical Centre Nijmegen
  More Information

No publications provided

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01246817     History of Changes
Other Study ID Numbers: UMCNONCO200903
Study First Received: November 22, 2010
Last Updated: April 10, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
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).

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sirolimus
Everolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 20, 2014