Single Agent Temsirolimus (Torisel®) in Chemotherapy-naïve Castration-Resistant Prostate Cancer Patients

• ClinicalTrials.gov Identifier: NCT00919035
• Recruitment Status: Completed
• First Posted: June 11, 2009
• Results First Posted: April 7, 2014
• Last Update Posted: June 30, 2014
• Sponsor: Oncology Specialists, S.C.
• Collaborator: Wyeth is now a wholly owned subsidiary of Pfizer
• Information provided by (Responsible Party): Dr. Sigrun Hallmeyer, Oncology Specialists, S.C.

Tracking Information

• First Submitted Date: June 10, 2009
• First Posted Date: June 11, 2009
• Results First Submitted Date: February 28, 2014
• Results First Posted Date: April 7, 2014
• Last Update Posted Date: June 30, 2014
• Study Start Date: June 2009
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 19, 2014)

Overall Clinical Benefit From Torisel® in Chemotherapy-naïve Castration Resistant Prostate Cancer (CRPC). [ Time Frame: disease progression is assessed every 2 cycles, for up to 40weeks, per protocol, from the date of the first dose of study drug to the date the patient is taken off study ]

The overall clinical benefit is defined as the sum of complete response (CR), partial response (PR), and stable disease (SD). CR: is the disappearance of all measurable lesions including bone lesions detected on the bone scan, no evidence of new lesions, and no disease-related symptoms. PR: More than 30% decrease in the sum of longest diameter of measurable lesions compared to baseline. SD: Lesions should have no sufficient decrease for PR or CR and no sufficient increase to meet criteria for Progressive Disease (PD). PD: > 20% increase in the sum of longest diameter of measurable lesions compared to baseline, and/or evidence of new lesions on imaging studies OR The appearance of 2 or more new bony lesions on a bone scan is satisfactory for PD. Newly developed cord compression or pathologic fracture is defined as PD.

• Original Primary Outcome Measures (submitted: June 10, 2009): To determine the overall clinical benefit with Torisel® in chemotherapy-naïve CRPC. The overall clinical benefit is defined as the sum of complete response, partial response, and stable disease [ Time Frame: disease progression is assessed every 2 cycles ]

Current Secondary Outcome Measures (submitted: June 19, 2014)

• Time to Disease Progression [ Time Frame: Disease progression is assessed every 2 months, for up to 40 weeks, measured from day one of protocol treatment until the date the patient is off study. ]
  Time to disease progression is defined as the length of time from when the patient starts the study till disease progression. Disease progression is defined as more than 20% increase in the sum of longest diameter of measurable lesions compared to baseline, and/or evidence of new lesions on imaging studies. Or the appearance of 2 or more new bony lesions on a bone scan. Or newly developed cord compression or pathologic fracture.
• Does the Prostate Specific Antigen (PSA) Doubling Times Change Before and After Treatment [ Time Frame: evaluate PSA doubling time pre study to actual doubling time while on study - calculated from start of study up to 10 cycles or 40 weeks. ]
  PSA Doubling time is defined as the length of time that it takes for an individual patients PSA to double. PSA doubling times were calculated using the medial records at study entry for each patient. While the patient was on study their PSA doubling times were also calculated.

Original Secondary Outcome Measures (submitted: June 10, 2009)

• To evaluate the time to disease progression [ Time Frame: Proportion of patients alive at 1, 2 and 3 years ]
• To investigate the toxicity and tolerability using the NCI CTCAE criteria [ Time Frame: throughout the time the patient is on study ]
• To evaluate the time to systemic chemotherapy and time to alternative therapy [ Time Frame: actual day patient starts next treatment ]
• To assess the changes in PSA doubling time before and after treatment [ Time Frame: evaluate time frame using dates and actual PSA values ]
• Biochemical responses measured by serum PSA changes [ Time Frame: Using actual PSA values and dates from start of study - lasting through out study ]
• Proportion of patients alive at 1, 2, & 3 years [ Time Frame: use actual data ]
• Impact of treatment on quality of life (QOL) and pain scores using the MDASI & BPI published scales [ Time Frame: baseline, C3 & C5 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Single Agent Temsirolimus (Torisel®) in Chemotherapy-naïve Castration-Resistant Prostate Cancer Patients
• Official Title: Phase II Study Investigating the Toxicity and Efficacy of Single Agent Temsirolimus (Torisel®) in Chemotherapy-naïve Castration-Resistant Prostate Cancer Patients
• Brief Summary: This is a single institution, open label, phase II study in androgen-independent prostate cancer patients who are chemotherapy-naïve. Patients will receive Torisel® 25 mg weekly. Treatment continues until disease progression, patient's withdrawal, unacceptable toxicity or the investigator's discretion.

Detailed Description

This is an open label phase II study conducted in patients who have androgen-independent and castration-resistant prostate cancer but who have not received systemic chemotherapy. Investigational therapy such as vaccines, immunotherapy, and some oral targeted agents are NOT considered chemotherapy. Prior use of steroids is not an exclusion criterion.

Patients who meet the inclusion criteria will be allowed to participate. Enrolled patients will receive single agent Torisel® at 25 mg weekly. Every 4 weeks of therapy will constitute one cycle of treatment. Patients will continue on therapy until voluntary withdrawal, toxicity, progression, or the investigator's discretion. Patients will be followed for 3 years after discontinuation of Torisel®.

Patients are allowed to receive intravenous or oral bisphosphonates for their bone metastases and are advised to continue androgen blockade while on study.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer

Intervention

Drug: torisel

Patients will receive Torisel 25 mg weekly. Treatment continues until disease progression, patient's withdrawal, unacceptable toxicity or the investigator's discretion

Other Name: Temsirolimus

Study Arms

Experimental: Torisel

Single Agent Temsirolimus (Torisel®)

Intervention: Drug: torisel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 28, 2014): 21
• Original Estimated Enrollment (submitted: June 10, 2009): 24
• Actual Study Completion Date: October 2013
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form.
2. Age 18 years at the time of signing the informed consent form.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Documented prostate cancer regardless of the Gleason score
5. Patients should be considered hormone refractory and castration-resistant. They must fail LHRH analogues, and anti-androgen withdrawal trial. Failure is confirmed by an increase in PSA value of 10% or more than the value immediately before.
6. Patients must have measurable disease either biochemically (using PSA) and/or using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria for visceral organ involvement and/or bone disease. If there is no disease to follow on scans a PSA value of at least 5 ng per milliliter needs to be present at baseline to be evaluated for PSA response.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or less.
8. Adequate liver function tests with ALT/AST being < 3x normal, total bilirubin of 1.5 or less, and adequate renal function measured by a creatinine of 2.0 mg/dl or less. Alkaline phosphatase values are never exclusion criteria if it is deemed related to bone metastases.

9. Patients need to have adequate bone marrow function.

   • absolute neutrophil count (ANC) of 1000 or above,
   • Hgb of 9.0 g/dl or above,
   • Platelets of 100,000 or above. If other causes are affecting plts counts such as autoimmune disorders, patients are allowed on study. Patients with inadequate bone marrow function that is deemed related to bone marrow involvement with prostate cancer (cytopenias are due to extensive marrow infiltration with prostate cancer) are allowed at the investigator's discretion.
10. Patients with other malignancies are allowed as long as there is no evidence of the other malignancy present at entry time, and it has been 3 years or more since the treatment for the other disorder was completed. Patients with non-melanoma skin cancers are allowed to participate in the study.
11. Investigational therapy such as vaccines, immunotherapy, and oral targeted agents are allowed on this study as long as their last exposure was 4 weeks prior to study entry. These agents are not considered an exclusion criteria as they are not considered standard chemotherapy.
12. Patients with known bone metastases are allowed to receive intravenous bisphosphonates such as aredia or zometa. Patients on oral bisphosphonates are also allowed.
13. All study participants are encouraged to continue androgen deprivation with an LHRH analogue.
14. Patients must agree to use a latex condom during sexual contact with a female of childbearing potential, even if they have had a successful vasectomy and despite the fact that they are on androgen deprivation.
15. Last treatment for prostate cancer should be at least 4 weeks ago

Exclusion Criteria:

1. Prior systemic chemotherapy for castration Resistant Prostate Cancer (CRPC)
2. Prior exposure to temsirolimus (TEM)
3. Known HIV positive status or infectious hepatitis, type A, B, or C.
4. Known brain metastases.
5. Steroids are allowed concomitantly ONLY IF they are taken for another chronic medical condition (Such as chronic obstructive pulmonary disease , Multiple sclerosis…etc)
6. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing and understanding the informed consent form.
7. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he were to participate in the study or confounds the ability to interpret data from the study.
8. Use of any other experimental drug or therapy within 28 days of baseline.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00919035
• Other Study ID Numbers: OSRI 0901
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Dr. Sigrun Hallmeyer, Oncology Specialists, S.C.
• Study Sponsor: Oncology Specialists, S.C.
• Collaborators: Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

• Principal Investigator: Chadi Nabhan, MD; Oncology Specialists, S.C.

• PRS Account: Oncology Specialists, S.C.
• Verification Date: June 2014