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Cixutumumab and Temsirolimus in Treating Patients With Metastatic Prostate Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01026623
First received: December 3, 2009
Last updated: November 25, 2014
Last verified: September 2014
  Purpose

This phase I/II trial is studying the side effects of giving cixutumumab together with temsirolimus and to see how well it works in treating patients with metastatic prostate cancer. Monoclonal antibodies, such as cixutumumab, 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. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cixutumumab together with temsirolimus may kill more tumor cells.


Condition Intervention Phase
Hormone-Resistant Prostate Cancer
Prostate Adenocarcinoma
Recurrent Prostate Carcinoma
Stage IV Prostate Cancer
Biological: Cixutumumab
Other: Diagnostic Laboratory Biomarker Analysis
Drug: Temsirolimus
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Anti-IGF-IR Monoclonal Antibody IMC-A12 Plus mTOR Inhibitor Temsirolimus (CCI-779) in Metastatic Castration-Resistant Prostate Cancer (CRPC)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Tumor response rate [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]
    Defined by modified Response Evaluation Criteria in Solid Tumors (RECIST) and/or the proportion of patients who achieve a greater than 50% reduction in serum PSA compared to baseline.

  • cTTP [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]
    Defined as the time from the first day of treatment to the earliest one of the following: tumor progression by RECIST; unequivocal evidence of progression by bone scan (at least two new lesions with confirmation at subsequent imaging); new skeletal events; symptomatic progression; or other clinical events attributable to prostate cancer that necessitate major interventions.


Secondary Outcome Measures:
  • Maximal percentage decrease in serum PSA [ Time Frame: From baseline to week 12 ] [ Designated as safety issue: No ]
    Summarized using descriptive statistics (eg, mean, standard deviation, median, minimum, maximum).

  • Change in PSA doubling time [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    Compared using descriptive statistics.

  • Duration of effect [ Time Frame: From the time of first dose until the time of progression, assessed up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]
    Summarized using descriptive statistics.

  • Progression-free survival [ Time Frame: From the time of first dose until objective tumor progression or death, assessed up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]
    Summarized using descriptive statistics. Median PFS over time will be determined using Kaplan Meier method.

  • Rate of adverse events according to NCI CTCAE version 4.0 [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: Yes ]
    Adverse event summaries will be organized by body system, frequency of occurrence, intensity (ie, severity grade), and causality or attribution.


Estimated Enrollment: 48
Study Start Date: October 2009
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cixutumumab, temsirolimus)
Patients receive cixutumumab IV over 60-70 minutes and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Biological: Cixutumumab
Given IV
Other Names:
  • Anti-IGF-1R Recombinant Monoclonal Antibody IMC-A12
  • IMC-A12
Other: Diagnostic Laboratory Biomarker Analysis
Correlative studies
Drug: Temsirolimus
Given IV
Other Names:
  • CCI-779
  • Torisel

Detailed Description:

PRIMARY OBJECTIVES:

I. To confirm the safety and tolerability of IMC-A12 (cixutumumab) and temsirolimus using the recommended phase II dose level for advanced solid tumors in chemo-naive patients with metastatic castration-resistant prostate cancer and a rising prostate-specific antigen (PSA). (Phase I) II. To confirm the safety and tolerability of IMC-A12 and temsirolimus given on an every three weeks dosing schedule. (Phase I Extension) II. To determine the tumor response rate and/or composite time to progression (cTTP) for chemotherapy-naive patients with castration-resistant prostate cancer (CRPC) receiving the combination of IMC-A12 and CCI-779 (temsirolimus). (Phase II)

SECONDARY OBJECTIVES:

I. To determine the maximal percent decrease in PSA from baseline. II. To determine the change in PSA doubling time (PSADT). III. To determine the time to PSA progression and 6-month progression-free survival (PFS).

IV. To determine the rate of adverse events.

EXPLORATORY OBJECTIVES:

I. To evaluate changes in circulating tumor cell (CTC) numbers with time. II. To evaluate IGF1R and androgen receptor (AR) in CTCs and correlate with response.

III. To evaluate profiling CTCs at the molecular level by polymerase chain reaction (PCR) for prostate cancer-specific genes.

IV. To explore the association between clinical outcomes, administration of therapy, and serial fludeoxyglucose F 18 (FDG)-positron emission tomography (PET) imaging.

V. To correlate fluorine F 18 FMDHT (18-FDHT)-PET imaging findings with outcome measures of response.

VI. To perform tumor biopsies and evaluate biomarkers that may correlate with active feedback and tumor response to therapy, including anti-insulin receptor substrate 1 (IRS-1), anti-IRS-2, phosphorylated (p) protein kinase B (Akt)(S473), p-ribosomal protein S6 kinase (70/S6K), anti-phospho-AKT1 substrate 1 (proline-rich) (PRAS 40), and phosphatase and tensin homolog gene (PTEN) status.

OUTLINE: This is a multicenter study.

Patients receive cixutumumab intravenously (IV) over 60-70 minutes and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the prostate

    • Distant metastases evaluable by radionuclide bone scan, CT scan, or magnetic resonance imaging (MRI) within the past 28 days
  • Evidence of progressive disease during androgen-deprivation therapy (including a trial of antiandrogen-withdrawal therapy), as defined by ≥ 1 of the following criteria:

    • Progressive measurable disease using conventional solid tumor criteria
    • Bone scan progression, defined as ≥ 2 new lesions on bone scan
    • Increasing PSA, defined as ≥ 2 consecutive rising PSA values over a reference value taken ≥ 1 week apart (the third PSA value must be greater than the second PSA value, if not, a fourth PSA value must be greater than the second PSA value)
  • Castrate levels of serum testosterone (i.e., ≤ 50 ng/dL)
  • No known brain metastases
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 OR Karnofsky PS 70-100%
  • Life expectancy > 6 months
  • Leukocytes ≥ 3,000/μL
  • Absolute neutrophil count (ANC) ≥ 1,500/μL
  • Platelet count ≥ 100,000/μL
  • Hemoglobin ≥ 9 g/dL
  • Total bilirubin ≤ 2 times upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN
  • Serum creatinine ≤ 1.5 times ULN
  • Creatinine clearance ≥ 50 mL/min
  • Able to adhere to the study visit schedule and other study requirements
  • Fertile patients must use effective contraception before, during, and for 3 months after completion of study treatment
  • Adequate lung function (pulmonary function test ≥ 70% for diffusion capacity of the lung for carbon monoxide [DLco])
  • No poorly controlled diabetes mellitus

    • Patients with a history of diabetes are eligible provided their blood glucose is normal (i.e., fasting blood glucose < 120 mg/dL or < ULN) and they are on a stable dietary or therapeutic regimen
  • No other malignancy within the past 3 years except for treated basal cell or squamous cell carcinoma of the skin or superficial transitional cell carcinoma of the bladder
  • No uncontrolled major illness including, but not limited to, any of the following:

    • Active infection, including human immunodeficiency virus (HIV) infection or viral hepatitis
    • Symptomatic congestive heart failure (class III or IV)
    • Unstable angina pectoris
    • Myocardial infarction or acute coronary syndrome within the past year
    • Serious cardiac arrhythmia
    • Significant lung disease
    • Major psychiatric illness
  • No other concurrent anticancer agents or treatments
  • No prior chemotherapy, except for neoadjuvant chemotherapy
  • No prior anti-insulin-like growth factor receptor (IGFR) agents or mammalian target of rapamycin (mTOR) inhibitors
  • No prior strontium-89, rhenium-186, rhenium-188, or samarium-153 radionucleotide therapy
  • Prior standard-dose radiotherapy to the pelvis for prostate cancer and/or additional external-beam radiotherapy to metastatic sites allowed
  • More than 4 weeks since prior surgery, radiotherapy, combined androgen blockade (excluding single-agent gonadotropin releasing-hormone agonists/antagonists), or investigational therapies
  • No concurrent second-line hormonal agents, including ketoconazole, diethylstilbestrol, other estrogen-like agents, or finasteride
  • No concurrent corticosteroids unless patient is on a stable maintenance dose of hydrocortisone (≤ 30 mg/day) for ≥ 3 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01026623

Locations
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Investigators
Principal Investigator: Dana Rathkopf Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01026623     History of Changes
Other Study ID Numbers: NCI-2011-01406, NCI-2011-01406, CDR0000659064, 09-117, 8147, P30CA008748, U01CA069856
Study First Received: December 3, 2009
Last Updated: November 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Prostatic Diseases
Urogenital Neoplasms
Antibodies, Monoclonal
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014