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

NCT01083368 | Completed Phase 1 Results DMC

• 3 other identifiers: CASE7808NCI-2010-00308CASE7808-CC527
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief 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. 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.

Conditions

Prostate Cancer

Keywords

adenocarcinoma of the prostate; hormone-resistant prostate cancer; recurrent prostate cancer; stage IV prostate cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  at 24 weeks

• 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.

  change from baseline to 12 weeks

Secondary Outcomes (3)

• Time to Clinical Progression

  12 weeks

• Overall Survival

  baseline to end of study, up to 3.5 years

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

  at 24 weeks

Other Outcomes (2)

• Presence of Circulating Tumor Cells and Single Nucleotide Polymorphism Status

  at end of treatment

• Prostate Specific Androgen (PSA)

  at baseline

Study Arms (1)

Arm 1: Combination of temsirolimus and AVASTIN

EXPERIMENTAL

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.

Drug: temsirolimus; Biological: bevacizumab; Genetic: polymorphism analysis; Other: laboratory biomarker analysis

Interventions

temsirolimus DRUG

Given IV

Also known as: CCI-779, cell cycle inhibitor 779, rapamycin analog CCI-779, Torisel

Arm 1: Combination of temsirolimus and AVASTIN

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, anti-VEGF rhuMAb, Avastin, recombinant humanized anti-VEGF monoclonal antibody, rhuMAb VEGF

Arm 1: Combination of temsirolimus and AVASTIN

polymorphism analysis GENETIC

Correlative studies

Arm 1: Combination of temsirolimus and AVASTIN

laboratory biomarker analysis OTHER

Correlative studies

Arm 1: Combination of temsirolimus and AVASTIN

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (3)

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

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

CCF-Willoughby Hills

Willoughby Hills, Ohio, 44094, United States

Location

Related Publications (1)

• 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.

  PMID: 30402678 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

temsirolimus; Sirolimus; Bevacizumab; Amplified Fragment Length Polymorphism Analysis

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; DNA Fingerprinting; Genetic Techniques; Investigative Techniques; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques

Results Point of Contact

• Title: Jorge Garcia MD
• Organization: Case Comprehensive Cancer Center

garciaj4@ccf.org

216-444-7774

Study Officials

• Jorge Garcia, MD

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• Matthew Cooney, MD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2010
• First Posted: March 9, 2010
• Study Start: January 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: October 1, 2014
• Last Updated: August 21, 2019
• Results First Posted: August 21, 2019

Record last verified: 2019-08

Locations

US (3)