Everolimus (RAD001, Afinitor®) and Cyclophosphamide in Castration and Docetaxel resistant Prostate Cancer, a proof of principle Phase II study.

Phase 2

Withdrawn

• Conditions: Cancer of the prostate; prostatic neoplasm.; 10038597

• Registration Number: NL-OMON35076
• Lead Sponsor: ederlands Kanker Instituut

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: Withdrawn
• Sex: Not specified
• Target Recruitment: 20

Inclusion Criteria

- Prostate cancer diagnosis and a rising PSA under castrate serum testosterone levels (2 rises
in a period of at least 3 months), PSA > 10ng/ml.
- At least one prior cycle of Docetaxel treatment.
- ECOG performance status 0-2.
- Locally accessible prostate cancer for TRUS-guided biopsies.
- Written informed consent.
- Laboratory requirements:
a) Hematology:
* Hemoglobin > 5 mmol/L
* Platelet count * 100,000/*L
* No leucopenia
b) Hepatic function:
* AST and ALT * 2.5 times upper limit of normal (ULN)
* Bilirubin * 1.5 times ULN
c) Renal function:
* Calculated GFR (Cockroft) * 60 ml/min
* PT/PTT normal (no anticoagulants)
- Fertile patients must use effective contraception during and for 6 months after completion of
study therapy.

Exclusion Criteria

- Small cell pathology.
- Allergy to Everolimus or cyclophosphamide or components of Afinitor ® or Endoxan ®.
- Co-medication interfering with CYP3A4 activity.
- Gastrointestinal (GI) disease, condition, or symptoms that may significantly impair GI function
and alter the absorption of Everolimus, including any of the following:
o Ulcerative disease
o Vomiting
o Diarrhea
o Malabsorption syndrome
- Other active malignancy or malignancy at * 30% risk for relapse after completion of therapy,
except nonmelanoma skin cancer .
- Recent (within 2 weeks) surgery.
- Uncontrolled concurrent illness including, but not limited to, any of the following:
o Ongoing or active infection (e.g., bacterial, viral or fungal)
o Severely impaired lung function
o Uncontrolled diabetes (fasting serum glucose > 1.5 times ULN)
o Liver disease (e.g., cirrhosis, chronic active hepatitis, or chronic persistent hepatitis)
o Symptomatic congestive heart failure
o Unstable angina pectoris
o Cardiac arrhythmia
- Lower urinary tract obstruction not treated with bladder catheterisation.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>In order to investigate the mTOR inhibition in the prostate by Everolimus and<br /><br>the possible synergistic interaction with low dose, metronomic, oral<br /><br>Cyclophosphamide treatment, phophorylation of 4eBP1 and p70S6K will be assessed<br /><br>in prostate biopsies of prostate cancer patients.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>PSA response<br /><br>Toxicity of the combined Everolimus and Cyclophosphamide treatment</p><br>