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Prostate CancerPhase 1/2NCT01083368

Temsirolimus and Bevacizumab in Hormone-Resistant Metastatic Prostate Cancer That Did Not Respond to Chemotherapy

A Phase 1/2 study testing temsirolimus, bevacizumab and polymorphism analysis in people with Prostate Cancer, run by Case Comprehensive Cancer Center at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
temsirolimus, bevacizumab and polymorphism analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
3 sitesUnited States
Study dates
Jan 2009to Oct 2014
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Understand and voluntarily sign an informed consent form
  • Patients with histologically confirmed adenocarcinoma of the prostate
  • Patients must have evidence of chemotherapy-refractory metastatic CRPC following standard antiandrogen withdrawal (AAWD); CRPC will be defined as patients with metastatic prostate cancer with radiologic evidence of metastases on either bone scan, plain x-rays, CT scans, chest x-ray, and castrate levels of testosterone ( =< 50 mg/dL)
  • All patients must be receiving ongoing therapy to ensure testicular androgen suppression (LHRH therapy or bilateral orchiectomy)
  • Patients must have received prior Docetaxel-based or Mitoxantrone-based chemotherapy; previous chemotherapy treatments must be completed at least 4 weeks prior to screening, and patients must not have any residual therapy-related toxicity present at screening
  • Patients must be off any steroids 7 days prior to the initiation of treatment
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  • Patients must have evidence of disease progression defined as any of the following:
  • a) New sites of metastatic disease on radiographic imaging (bone scan or CT scan of chest/abdomen/pelvis) as determined by the referring physician
  • b) PSA progression, defined as 2 consecutive PSA rise at least 2 weeks apart with PSA value over a baseline level of at least 5.0 ng/mL, confirmed after an interval of at least two weeks
  • ECOG performance status 0-2 (Eastern Cooperative Oncology Group)
  • Absolute neutrophil count >= 1500/uL
  • Hemoglobin >= 8 g/dL (blood transfusion not permitted within 2 weeks prior to first dose of treatment)
  • Platelets >= 100,000/uL
  • Serum creatinine =< 1.5 x ULN
  • Total bilirubin =< 1.5 x ULN
  • AST (aspartate aminotransferase-SGOT) and ALT (SGPT) that are =< 2.5 x ULN (5 x ULN in patients with liver metastasis)
  • Fasting cholesterol =< 350mg/dL and fasting triglycerides =< 400mg/dL
  • Hemoglobin A1c (HgbA1c) < 10% (optimal therapy permitted)
  • Therapeutic INR/PT for those patients receiving oral anticoagulation
  • Urine protein:creatinine ratio (UPC) =< 1.0 at screening
  • QTc interval =< 450 msec for males and =< 470 msec for females
  • The use of cholesterol medications is allowed during the study
  • Patients with a history of a prior malignancy are eligible provided they were treated with curative intent and have been disease-free for the time period considered appropriate by the treating physician
  • Sexually active men whose sexual partners are women of childbearing potential must agree to use a medically acceptable form of barrier contraception or abstinence during their participation in the study and for at least six weeks after study drug discontinuation
  • Patients on stable doses of bisphosphonates that show subsequent tumor progression may continue on this medication; however, patients are not allowed to initiate bisphosphonate therapy within 4 weeks prior to starting therapy or throughout the study
  • Prior radiopharmaceuticals (strontium, samarium) must be completed at least 8 weeks prior to treatment initiation in this study and all major side effects resolved to =< grade 1
  • Patients receiving any other hormonal therapy, including any dose of Megestrol acetate (Megace), Proscar (finasteride), any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES), must discontinue the agent for at least 4 weeks prior to enrollment
  • Life expectancy of at least 12 weeks
  • Written informed consent/HIPAA (Health Insurance Portability and Accountability Act)authorization must be provided prior to the performance of any study-related procedures

Who cannot join

  • Prior treatment with AVASTIN, temsirolimus, everolimus or sirolimus
  • Evidence of current or prior central nervous system (CNS) metastases or any imaging abnormality indicative of CNS metastases; patients with history of cord compression are eligible provided they had either palliative radiation therapy or surgery, have NO neurologic symptoms (as determined by treating physician), have stable spinal disease by scans and are off any steroids prior to initiating study drug (at least 7 days)
  • Major surgery or radiation therapy within 28 days prior to screening (Palliative radiotherapy to painful bone lesions is allowed within 14 days prior to study entry); subject must have recovered from prior surgery and radiation
  • Significant cardiovascular disease defined as congestive heart failure (NYHA Class II, III, or IV), angina pectoris requiring nitrate therapy, or myocardial infarction within the last 6 months
  • Inadequately controlled hypertension (defined as a blood pressure of >= 150 mmHg systolic and/or >= 100 mmHg diastolic on medication), or any prior history of hypertensive crisis or hypertensive encephalopathy
  • History of stroke or transient ischemic attack within 6 months prior to screening
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  • Significant vascular disease (e.g., aortic aneurysm, aortic dissection), or symptomatic peripheral vascular disease
  • Known congenital long QT syndrome, history of Torsade de pointes or ventricular tachycardia
  • Known pulmonary hypertension or pneumonitis
  • More than 1 episode of DVT/PE within the last 6 months
  • Evidence or history of bleeding diathesis or coagulopathy
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to screening
  • Supplements or complementary medicines/botanicals are not permitted while on protocol therapy, except for any combination of the following: conventional multivitamin supplements; selenium; lycopene; soy supplements; patients should review the label with their doctor prior to enrollment, and discontinue disallowed agents prior to study enrollment; patients taking St. John's Wort need to discontinue its use at least 7 days prior to initiating trial
  • Serious intercurrent infections or non-malignant medical illnesses including uncontrolled autoimmune disorders
  • Psychiatric illnesses/social situations that would limit compliance with protocol requirements
  • Known contraindication to receive temsirolimus or AVASTIN
  • Use of any other experimental drug or therapy within 28 days of baseline
  • Immunocompromised subjects, including known seropositivity for human immunodeficiency virus (HIV), or current or chronic hepatitis B and/or hepatitis C infection (as detected by positive testing for hepatitis B surface antigen [HbsAg] or antibody to hepatitis C virus [anti HCV] with confirmatory testing) (testing is not mandatory to be eligible for the study)
  • Anticancer therapies such as biologic therapy and chemotherapy, as well as radiation therapy or cancer surgery
  • Other current or recent (within 4 weeks prior to randomization) investigational agent
  • Rifampicin
  • Immunosuppressive therapies except steroids
  • Prophylactic use of white blood growth factors to support neutrophils
  • Concomitant treatment with agents that have CYP3A4 induction or inhibition potential should be voided

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106

  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44195

  • CCF-Willoughby Hills

    Willoughby Hills, Ohio, 44094

Other trials in United States

About this study

Official title: Phase I-II Study Evaluating the Safety and Clinical Efficacy of Temsirolimus and Avastin in Patients With Chemotherapy Refractory Castrate Resistant Prostate Cancer (CRPC)

RATIONALE: Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving temsirolimus together with bevacizumab may be a better way to block tumor growth.

PURPOSE: This phase I/II trial is studying the side effects and best dose of temsirolimus when given together with bevacizumab and to see how well it works in treating patients with hormone-resistant metastatic prostate cancer that did not respond to chemotherapy.

Read the detailed description

PRIMARY OBJECTIVES:

  1. The primary objective of the Phase I portion of this study is to determine the maximum tolerated dose (MTD) of temsirolimus in combination with AVASTIN in subjects with chemotherapy refractory metastatic CRPC.

II. The primary objective for the Phase II portion of this study is to evaluate the objective response frequency (PSA and RECIST-Response Evaluation Criteria in Solid Tumors-defined) of the combination of temsirolimus and AVASTIN in patients with chemotherapy refractory metastatic CRPC.

SECONDARY OBJECTIVES:

  1. To evaluate the effect of the combination of temsirolimus and AVASTIN on time to clinical progression and overall survival in patients with chemotherapy refractory metastatic CRPC.

II. To further evaluate the safety of temsirolimus given in combination with AVASTIN in chemotherapy refractory metastatic CRPC patients at the dose established in our phase I safety phase.

III. To determine the presence of circulating tumor cells (CTCs) and status of single nucleotide polymorphism (SNPs) in CRPC patients. (Exploratory)

OUTLINE: Patients receive temsirolimus IV over 30-60 minutes once weekly and bevacizumab IV over 30-90 minutes once every two weeks . Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 28 days.

Conditions
Prostate Cancer
Being tested
temsirolimus, bevacizumab, polymorphism analysis, laboratory biomarker analysis
Keywords
adenocarcinoma of the prostate, hormone-resistant prostate cancer, recurrent prostate cancer, stage IV prostate cancer
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • temsirolimusDrug

    Also called CCI-779, cell cycle inhibitor 779, rapamycin analog CCI-779, Torisel

    Given IV

  • bevacizumabBiological

    Also called anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, anti-VEGF rhuMAb, Avastin

    Given IV

  • polymorphism analysisGenetic

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01083368
Study groupRoleWhat they receive
Arm 1: Combination of temsirolimus and AVASTINExperimentalPatients receive temsirolimus IV over 30-60 minutes once weekly and bevacizumab IV over 30-90 minutes once every two weeks . Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: temsirolimus; Biological: bevacizumab; Genetic: polymorphism analysis; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) of Temsirolimus (Phase I)

    Participants received temsirolimus (20mg or 25mg IV weekly) in combination with a fixed dose of IV bevacizumab (10mg/kg every 2 weeks). The MTD was determined to be the dose at which no unacceptable toxicities were observed.

    Measured: at 24 weeks

  2. Objective Response (Dose Level 2)

    PSA (Prostate-Specific Antigen) test will be performed every 4 weeks prior to receiving treatment. PSA response will be measured as the number of participants that had a decline observed from baseline.

    Measured: change from baseline to 12 weeks

Secondary outcomes (3)

  1. Time to Clinical Progression

    To evaluate the effect of the combination of temsirolimus and AVASTIN on time (in months) to clinical progression from start of treatment. Progressive Disease according to RECIST Criteria is defined as : At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions

    Measured: 12 weeks

  2. Overall Survival

    Time in months from on study to time of death

    Measured: baseline to end of study, up to 3.5 years

  3. Number of Patients With Toxicity as Assessed by CTCAE v3.0 (Common Toxicity Criteria for Adverse Effects)

    To further evaluate the safety of temsirolimus given in combination with AVASTIN in chemotherapy refractory metastatic CRPC patients at the dose established in our phase I safety phase. Specific toxicities are listed in the SAE and AE results.

    Measured: at 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Mar 2010 (estimated)
  2. Study startJan 2009
  3. Primary completionDec 2011
  4. Study completionOct 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01083368
Sponsor's protocol ID
CASE7808
Other IDs
NCI-2010-00308, CASE7808, CASE7808-CC527
Status last verified
Aug 2019
First submitted
5 Mar 2010
Last updated
21 Aug 2019
Data monitoring committee
Yes

Publications

  • Barata PC, Cooney M, Mendiratta P, Gupta R, Dreicer R, Garcia JA. Phase I/II study evaluating the safety and clinical efficacy of temsirolimus and bevacizumab in patients with chemotherapy refractory metastatic castration-resistant prostate cancer. Invest New Drugs. 2019 Apr;37(2):331-337. doi: 10.1007/s10637-018-0687-5. Epub 2018 Nov 7.

    PubMed 30402678

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing temsirolimus, bevacizumab and polymorphism analysis in people with Prostate Cancer, run by Case Comprehensive Cancer Center at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) of Temsirolimus (Phase I) (time frame: at 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01083368, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2019.

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