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Phase II Trial of Carboplatin and RAD001 in Metastatic Castrate Resistant Prostate Cancer (CRPC) Pretreated With Docetaxel Chemotherapy.

Phase 2
18 Years
Open (Enrolling)
Prostate Cancer

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Trial Information

Phase II Trial of Carboplatin and RAD001 in Metastatic Castrate Resistant Prostate Cancer (CRPC) Pretreated With Docetaxel Chemotherapy.



- To evaluate the time to progression (TTP) achieved with carboplatin and everolimus in
patients with castrate resistant metastatic prostate cancer that progressed after
docetaxel-based chemotherapy.


- To evaluate the safety of this regimen.

- To assess the PSA response rate in patients treated with this regimen.

- To evaluate the overall survival (OS) outcome in these patients.

- To investigate the association of TTP and PSA response rate with correlative markers,
such as phospho mTOR, pAKT, and p70S6.

- To evaluate the pharmacokinetics of this regimen.

- To explore the association of TTP, OS, and circulating tumor tumor cell count.

OUTLINE: Patients receive carboplatin IV over 30-60 minutes on day 1, oral prednisone twice
daily on days on days 1-21, and oral everolimus once daily on days 2-21 of course 1 and on
days 1-21 of subsequent courses. Courses repeat every 21 days in the absence of disease
progression or unacceptable toxicity.

Blood and tumor tissue samples are collected periodically for pharmacodynamic,
pharmacokinetic, and biomarker analysis.

After completion of study treatment, patients are followed up every 3 months.

Inclusion Criteria


- Histologically confirmed metastatic adenocarcinoma of the prostate

- Objective disease progression or rising PSA despite androgen deprivation therapy and
antiandrogen withdrawal (when applicable)

- Progressed after ≥ 1 prior docetaxel-based chemotherapy regimen for metastatic

- Patients with measurable disease* must have either rising PSA, increase in size
of the lesion(s), or both

- Patients with rising PSA as the only evidence of disease progression must
demonstrate a rising trend with 2 successive elevations ≥ 1 week apart

- Patients with no measurable disease must have a PSA ≥ 5 ng/mL or new areas of
bony metastases on bone scan NOTE: *There is no minimum PSA requirement for
patients with measurable disease

- Documented to be castrate with a testosterone level of ≤ 0.5 ng/mL

- Leuteinizing hormone-releasing hormone agonist therapy must be continued, if
required to maintain castrate levels of testosterone

- No uncontrolled brain or leptomeningeal metastases, including patients who continue
to require glucocorticoids for brain or leptomeningeal metastases


- Zubrod performance status 0-1

- ANC ≥ 1,500/mm^3

- Hemoglobin ≥ 9.0 g/dL

- Platelet count ≥ 100,000/mm^3

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- Calculated creatinine clearance ≥ 50 mL/min OR serum creatinine ≤ 2 mg/dL

- AST and/or ALT ≤ 2.5 times ULN if alkaline phosphatase normal OR alkaline phosphatase
≤ 4 times ULN if AST and/or ALT normal (for patients without documented bone
metastases or for patients with liver metastases)

- AST and/or ALT < 2.5 times ULN, without regard to alkaline phosphatase levels (for
patients with documented bone metastases)

- Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤
2.5 times ULN (in the case that one or both of these thresholds are exceeded, the
patient is eligible only after initiation of appropriate lipid-lowering medication)

- Fertile patients must use effective contraception during and for ≥ 6 months after
completion of study treatment

- Willing and able to comply with this study

- Able to ingest oral medication

- No other malignancies except non-melanoma skin cancer or any other adequately treated
cancer in complete remission for ≥ 2 years

- No significant traumatic injury within the past 4 weeks

- No active (acute or chronic) or uncontrolled severe infections

- No severe and/or uncontrolled medical conditions or other conditions that could
affect study participation, including the following:

- NYHA class III-IV symptomatic congestive heart failure

- Unstable angina pectoris, symptomatic congestive heart failure, myocardial
infarction within the past 6 months, serious uncontrolled cardiac arrhythmia, or
any other clinically significant cardiac disease

- Severely impaired lung function as defined by spirometry and DLCO that is 50% of
the normal predicted value and/or oxygen saturation that is ≤ 88% at rest on
room air

- Uncontrolled diabetes as defined by fasting serum glucose > 1.5 times ULN

- Liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent

- Known history of HIV seropositivity, hepatitis B or C

- Impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of everolimus (e.g., ulcerative disease,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel

- Active, bleeding diathesis

- No known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus)
or to their excipients

- No history of noncompliance to medical regimens

- No uncontrolled diabetes mellitus


- See Disease Characteristics

- At least 1 prior docetaxel based regimen for metastatic disease

- Docetaxel based combination therapy or docetaxel alone considered as 1 regimen

- No more than 2 prior chemotherapy regimens for metastatic disease

- No prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)

- At least 6 weeks since prior bicalutamide or nilutamide

- At least 4 weeks since prior flutamide

- More than 4 weeks since prior and no other concurrent investigational drugs

- More than 4 weeks since prior and no other concurrent anticancer therapies (including
chemotherapy, radiotherapy, or antibody-based therapy)

- More than 4 weeks since prior and no concurrent major surgery (defined as requiring
general anesthesia) and recovered

- More than 1 week since prior and no concurrent immunization with attenuated live

- No concurrent chronic, systemic treatment with corticosteroids or other
immunosuppressive agents

- Topical or inhaled corticosteroids are allowed

- No concurrent prophylactic growth factors

- Concurrent bisphosphonate therapy allowed

Type of Study:


Study Design:

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

Outcome Measure:

Time to progression (TTP)

Outcome Time Frame:

Every 3 cycles (cycle = 21 days)

Safety Issue:


Principal Investigator

Ulka N. Vaishampayan, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Barbara Ann Karmanos Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

February 2010

Completion Date:

Related Keywords:

  • Prostate Cancer
  • hormone-resistant prostate cancer
  • recurrent prostate cancer
  • stage IV prostate cancer
  • adenocarcinoma of the prostate
  • Prostatic Neoplasms



Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
Weisberg Cancer Treatment CenterDetroit, Michigan  48334