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Phase Ib Study of Limited Androgen Ablation and Two Dose Levels of Temsirolimus (NSC#683864) in Patients With Prostate Cancer Who Have a Biochemical Relapse After Prostatectomy and/or Radiotherapy

Phase 1
Not Enrolling
Adenocarcinoma of the Prostate, Recurrent Prostate Cancer

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Trial Information

Phase Ib Study of Limited Androgen Ablation and Two Dose Levels of Temsirolimus (NSC#683864) in Patients With Prostate Cancer Who Have a Biochemical Relapse After Prostatectomy and/or Radiotherapy


I. To characterize safety and drug-related adverse events of two doses (15 and 25 mg) of
intravenous weekly temsirolimus combined with short term complete androgen ablation and to
select a favorable and tolerable dose for prostate cancer patients who experience
biochemical failure after prostatectomy and/or radiation therapy.


I. To archive tissue and blood components for future study of molecular markers of response
and disease progression.

II. To evaluate the effects of 2 dose levels of temsirolimus on changes in the
phosphorylation state of proteins in the mTOR pathway using western blots on peripheral
blood mononuclear cells (PBMCs).


Patients receive combined androgen ablation therapy comprising a luteinizing
hormone-releasing hormone analogue (i.e., leuprolide acetate intramuscularly once monthly or
goserelin subcutaneously every 3 months) and an oral anti-androgen drug (i.e., bicalutamide
or nilutamide once daily or flutamide 3 times daily) on days 1-90.* Beginning on day 60 of
hormonal therapy, patients receive temsirolimus IV over 30 minutes once weekly. Treatment
with temsirolimus continues for up to 36 weeks in the absence of disease progression or
unacceptable toxicity.

NOTE: *Patients may receive no more than 3 months of hormonal therapy, including therapy
initiated within 2 months of study entry.

After completion of study therapy, patients are followed at 30 days.

Inclusion Criteria:

- All patients must sign an informed consent indicating that they are aware of the
investigational nature of this study; patients must also have signed an authorization
for the release of their protected health information

- Patients must have histologically confirmed adenocarcinoma of the prostate recurring
after local therapy (radical prostatectomy and/or radiation therapy) as evidenced by
rising serum PSA

- Prostate-Specific Antigen (PSA) Doubling Time (PSADT) =< 12 months after local
therapy (prostatectomy and/or definitive radiation) as determined by linear
regression of all available PSA values within 6 months of initiation of androgen
ablation (for patients who underwent prostatectomy, at least one PSA measurement of
>= 1.0 ng/mL; for patients who underwent radiation, at least one PSA measurement of
>= 3.0 ng/mL and >= 150% postradiation nadir)

- No evidence of metastasis as determined by bone scan or computed tomography (CT) scan

- Initiation of Androgen Ablation of less than 8 weeks' duration prior to study entry
is permitted

- Leukocytes ≥ 3,000/mcl

- Absolute neutrophil count ≥ 1,000/mcl

- Hemoglobin ≥ 8.0g/dl

- Eligibility level for hemoglobin may be reached by transfusion

- Platelet count >= 100,000/μL

- Total bilirubin ≤1.5 X laboratory ULN

- AST and/or ALT ≤ 3 X laboratory ULN

- Creatinine ≤ 1.5 X laboratory ULN OR calculated creatinine clearance ≥ 60 ml/min/1.73
m^2 for patients w/creatinine levels above the laboratory ULN

- Serum cholesterol level < 350 mg/dl

- Triglyceride level < 300mg/dl

- ECOG performance status 0, 1 or 2

- The effects of Temsirolimus on the developing human fetus are unknown; for this
reason men must agree to use contraception from the time of study enrollment
continuing for the duration of study participation

- Patients must be registered in the MDACC institutional database prior to treatment
with study drug

- PSA < 40 ng/ml

Exclusion Criteria:

- Patients with histologic variants other than adenocarcinoma in the primary tumor

- Patients may not be receiving any other investigational agents

- Patients may not be receiving concomitant immunotherapy or immunosuppressive therapy

- Patients may not have received prior systemic treatment for prostate cancer (other
than no more than 3 months of prior treatment with androgen ablation in neoadjuvant
and/or adjuvant setting and at least a year must have elapsed since last
administration) unless initiation of Androgen Ablation of less than 8 weeks' duration
prior to study entry is permitted

- Patient with uncontrolled intercurrent illness including, but not limited to ongoing
or active infection requiring parenteral therapy on day 1 of protocol treatment,
symptomatic congestive heart failure resulting in a resting O2 saturation of < 92% on
room air, unstable angina pectoris, myocardial infarction within the previous 6
months, or use of ongoing maintenance therapy for life-threatening ventricular
arrhythmia, known pulmonary hypertension or pneumonitis

- Patients in a severely compromised immunological state, including being positive for
the human immunodeficiency virus (HIV) due to possible pharmacokinetic interactions
with HAART therapy

- Patients diagnosed with acute or chronic hepatitis B or C

- Patients using immunosuppressive agents, including intravenous corticosteroids,
within 3 weeks of study entry

- Patients must not have a history of any other cancer (except nonmelanoma skin
cancer), unless in complete remission and off of all therapy for that disease for a
minimum of 3 years

Type of Study:


Study Design:

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

Outcome Measure:

Safety, in terms of drug-related adverse events of two doses of temsirolimus following androgen ablation

Outcome Time Frame:

180 days

Safety Issue:


Principal Investigator

Christopher Logothetis

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

September 2007

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Prostate
  • Recurrent Prostate Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Prostatic Neoplasms



M D Anderson Cancer Center Houston, Texas  77030