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Hormone-Resistant Prostate CancerPhase 1/2NCT01026623

Cixutumumab and Temsirolimus in Treating Patients With Metastatic Prostate Cancer

A Phase 1/2 study testing Cixutumumab, Diagnostic Laboratory Biomarker Analysis and Temsirolimus in people with Hormone-Resistant Prostate Cancer and Prostate Adenocarcinoma, run by National Cancer Institute (NCI) at 4 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

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. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Cixutumumab, Diagnostic Laboratory Biomarker Analysis and Temsirolimus
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
4 sitesUnited States
Study dates
Oct 2009to Feb 2013
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

  • 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)
Show all 40Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

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)

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

  1. 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.

Being tested
Cixutumumab, Diagnostic Laboratory Biomarker Analysis, Temsirolimus
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • CixutumumabBiological

    Also called Anti-IGF-1R Recombinant Monoclonal Antibody IMC-A12, IMC-A12

    Given IV

  • Diagnostic Laboratory Biomarker AnalysisOther

    Correlative studies

  • TemsirolimusDrug

    Also called CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog

    Given IV

Study groups in NCT01026623
Study groupRoleWhat they receive
Treatment (cixutumumab, temsirolimus)ExperimentalPatients 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.
Receives: Biological: Cixutumumab; Other: Diagnostic Laboratory Biomarker Analysis; Drug: Temsirolimus

What is being measured

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

  1. cTTP

    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.

    This Outcome Measure is related to the Phase II portion of the Trial, which did not occur.

    Therefore, there is no data to report.

    Measured: Up to 4 weeks after completion of study treatment

  2. Tumor Response Rate

    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.

    Measured: Up to 4 weeks after completion of study treatment

Secondary outcomes (5)

  1. Change in PSA Doubling Time

    Compared using descriptive statistics. PSA doubling time is defined as the number of months it would take for PSA to increase two-fold. PSADT is inversely proportional to the slope of the regression line for the relation between log PSA and time. If this slope is negative, so the patient's PSA is going down over time, then the PSADT is negative.

    Measured: Week 1, Week 5, Week 9, Week 13, Week 17, Week 21 and Week 25

  2. Duration of Effect

    Summarized using descriptive statistics.

    Measured: From the time of first dose until the time of progression, assessed up to 4 weeks after completion of study treatment

  3. Maximal Percentage Change in Serum PSA as Compared to Week 12 Versus Baseline

    Summarized using descriptive statistics (eg, mean, standard deviation, median, minimum, maximum).

    Maximum percent change in serum PSA (i.e., 100%*[(value at Week 12 minus value at baseline)/value at baseline])

    Measured: From baseline to week 12

  4. Progression-free Survival

    Summarized using descriptive statistics. Median PFS over time will be determined using Kaplan Meier method.

    This Outcome Measure was related to the Phase 2 portion of the study, which did not occur.

    Therefore, there is no data to report.

    Measured: From the time of first dose until objective tumor progression or death, assessed up to 4 weeks after completion of study treatment

  5. Rate of Adverse Events According to NCI CTCAE Version 4.0

    Adverse event summaries will be organized by body system, frequency of occurrence, intensity (ie, severity grade), and causality or attribution.

    Please see Adverse Event/Serious Adverse Event Section.

    Measured: Up to 4 weeks after completion of study treatment

Timeline

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

  1. First posted4 Dec 2009 (estimated)
  2. Study startOct 2009
  3. Primary completionFeb 2013
  4. Study completionFeb 2013

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
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01026623
Sponsor's protocol ID
NCI-2011-01406
Other IDs
NCI-2011-01406, CDR0000659064, 09-117, 09-117, 8147, P30CA008748, U01CA069856
Status last verified
May 2019
First submitted
3 Dec 2009
Last updated
17 Jun 2019

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cixutumumab, Diagnostic Laboratory Biomarker Analysis and Temsirolimus in people with Hormone-Resistant Prostate Cancer and Prostate Adenocarcinoma, run by National Cancer Institute (NCI) at 4 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 40 inclusion and 0 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 17 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 17 Jun 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?

cTTP (time frame: Up to 4 weeks after completion of study treatment). 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 NCT01026623.

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 17 Jun 2019.

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