Impact of Temsirolimus Therapy on Circulating Tumor Cell Biology In Men With Castration Resistant Metastatic Prostate Cancer

NCT00887640 | Terminated Phase 2 Results DMC

• 1 other identifier: Pro00016256
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

Brief Summary

This is a single arm study of 11 men with treatment refractory metastatic Castrate Resistant Prostate Cancer (CRPC) who will receive temsirolimus IV at a dose of 25 mg weekly until progression. Progression will not include Prostate Specific Antigen (PSA) progression; however, upon PSA progression, the addition of an anti-androgen will be permitted. The primary objective of the study is to evaluate change in circulating tumor cell (CTC) counts over time in men with metastatic treatment-refractory CRPC in response to temsirolimus therapy.

Conditions

Prostate Cancer

Keywords

metastatic; Temsirolimus; prostate; cancer

Outcome Measures

Primary Outcomes (1)

• Change in Circulating Tumor Cell (CTC) Counts in Men With Metastatic Treatment-refractory Castration-resistant Prostate Cancer.

  Median percent change in CTC count from baseline to 8 weeks of treatment. Percent change was calculated by determining the percentage increase or decrease in CTC count from baseline.

  Baseline to 8 weeks

Secondary Outcomes (9)

• Percent Change in CTC Count From Baseline to 12 Weeks of Treatment.

  Baseline to 12 weeks

• Mean Percent of N-cadherin Expression at Baseline and 8 Weeks of Treatment.

  Baseline and 8 weeks

• Percent Change in LDH

  Baseline to 12 weeks

• Median Progression-Free Survival (PFS)

  2 years

• Maximum Rate of Change of Prostate-Specific Antigen (PSA).

  Baseline to 7 months

Study Arms (1)

Temsirolimus 25 mg

EXPERIMENTAL

Temsirolimus 25mg was administered by IV infusion each week (days 1, 8, 15, and 22 of each 28 day cycle). The infusion was to be administered over a period not less than 30 minutes and was to be completed within 60 minutes. Subjects were premedicated with 25 to 50 mg IV or PO diphenhydramine (or an alternative antihistamine in case of allergies) 30 minutes prior to the infusion.

Drug: Temsirolimus; Drug: Diphenhydramine

Interventions

Temsirolimus DRUG

dosage form: IV dosage, frequency and duration: 25mg weekly until clinical progression

Also known as: Torisel

Temsirolimus 25 mg

Diphenhydramine DRUG

Dosage form: IV or PO Dosage, frequency and duration: 25-50mg, 30 minutes prior to Temsirolimus infusion

Also known as: Benadryl

Temsirolimus 25 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed carcinoma of the prostate. Histologic evidence may be confirmed through local or metastatic biopsy review
• Radiographic Evidence of metastatic disease
• Evidence of disease progression despite castrate levels of testosterone.
• A circulating timor cell count using FDA approved CellSearch methodology of ≥ 10 per 7.5 cc whole blood, drawn within 4 weeks of study registration
• Serum PSA greater than or equal to 2ng/dl at registration
• At least 4 weeks since prior palliative radiation therapy and/or major surgery, and resolution of all toxic effects of prior therapy NCI Common Toxicity Criteria for Adverse Effects (CTCAE) Grade less than or equal to 1
• Age ≥ 18 years
• Adequate laboratory parameters
• Karnofsky Performance Status ≥ 60
• Life expectancy of at least 3 months

You may not qualify if:

• History of or active central nervous system metastases
• The use of cytotoxic, biologic, or hormonal therapies within 4 weeks of study entry.
• Subjects receiving known strong Cytochrome P450 3A4 (CYP3A4) isoenzyme inhibitors and/or inducers
• Major surgery, open biopsy, traumatic injury, or radiotherapy within 4 weeks of the screening visit
• Have not recovered from prior biopsy, surgery, traumatic injury, and/or radiation therapy.
• Presence of non-healing wound or ucer
• Grade ≥ 3 hemorrhage in the past month to study entry
• Hypertension with systolic blood pressure of ≥ 180 mmHg and/or diastolic pressure ≥ 100 mmHg (Anti-hypertensive medications are permitted)
• Subjects with Class 2-4 heart disease or any history of congestive heart failure with an ejection fraction \<50% or a recent (within 12 months) cardiovascular event.
• Anticoagulation with warfarin
• Diabetes mellitus with glycosylated hemoglobin A1c ≥ 10% despite therapy
• History of interstitial pneumonitis
• Subjects with active autoimmune disorder(s) being treated with immunosuppressive agents within 4 weeks prior to screening visit
• Subjects receiving immunosuppressive agents and those with chronic viral/bacterial/fungal illnesses. Replacement doses of corticosteroids are permitted.
• Active infection(s), active antimicrobial therapy or serious intercurrent illness.

Sponsors & Collaborators

• Duke University: lead
• National Comprehensive Cancer Network: collaborator

Study Sites (2)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis; Neoplasms

Interventions

temsirolimus; Diphenhydramine

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Dr. Andrew Armstrong
• Organization: Duke University Medical Center

andrew.armstrong@dm.duke.edu

919-668-8108

Study Officials

• Andrew Armstrong, MD, ScM

  Duke Unversity Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2009
• First Posted: April 24, 2009
• Study Start: July 1, 2009
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: February 26, 2014
• Results First Posted: January 10, 2014

Record last verified: 2013-01

Locations

US (2)