Cixutumumab and Temsirolimus in Treating Patients With Metastatic Prostate Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01026623
• Collaborator: (none)
• Enrollment: 16
• Locations: 4
• Arm: 1
• Duration (Months): 40
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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. 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 or Disease	Intervention/Treatment	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

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).

2. 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.

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

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

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

5. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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)
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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 CCI-779 Rapamycin Analog Cell Cycle Inhibitor 779 Rapamycin Analog Rapamycin Analog CCI-779 Torisel

Outcome Measures

Primary Outcome Measures

1. cTTP [Up to 4 weeks after completion of study treatment]

   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.

2. Tumor Response Rate [Up to 4 weeks after completion of study treatment]

   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.

Secondary Outcome Measures

1. Change in PSA Doubling Time [Week 1, Week 5, Week 9, Week 13, Week 17, Week 21 and Week 25]

   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.

2. Duration of Effect [From the time of first dose until the time of progression, assessed up to 4 weeks after completion of study treatment]

   Summarized using descriptive statistics.

3. Maximal Percentage Change in Serum PSA as Compared to Week 12 Versus Baseline [From baseline to week 12]

   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])

4. Progression-free Survival [From the time of first dose until objective tumor progression or death, assessed up to 4 weeks after completion of study treatment]

   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.

5. Rate of Adverse Events According to NCI CTCAE Version 4.0 [Up to 4 weeks after completion of study treatment]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
2	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
3	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
4	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Dana Rathkopf, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01026623
• Other Study ID Numbers: NCI-2011-01406; NCI-2011-01406; CDR0000659064; 09-117; 09-117; 8147; P30CA008748; U01CA069856
• First Posted: Dec 4, 2009
• Last Update Posted: Jun 17, 2019
• Last Verified: May 1, 2019

• Additional relevant MeSH terms: Prostatic Neoplasms; Sirolimus; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	IMC-A12: 6 mg/kg & Temsirolimus (CCI-779): 20 mg	IMC-A12: 6 mg/kg & Temsirolimus (CCI-779): 25 mg	IMC-A12: 20 mg/kg & Temsirolimus (CCI-779): 20 mg
Arm/Group Description	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Arm -1 (Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 20 mg IV over 30 min weekly)	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 25 mg IV over 30 min weekly	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=21 days:IMC-A12: 20 mg/kg IV over 90 min on day 1 Temsirolimus (CCI-779): 20 mg IV over 30 min on day 1 Fluorine-18 2-Fluoro-2-deoxy-D-Glucose (18F-FDG): 10 mCi IVB at baseline, within 1 week of the 1st txt, 12 weeks, 24 weeks, and end of study
Period Title: Overall Study
STARTED	6	5	5
COMPLETED	6	5	5
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	IMC-A12: 6mg/kg Temsirolimus 20 mg	IMC-A12: 6 mg/kg Temsirolimus 25 mg	IMC-A12: 20 mg/kg Temsirolimus 20 mg	Total
Arm/Group Description	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Arm -1 (Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 20 mg IV over 30 min weekly)	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 25 mg IV over 30 min weekly	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=21 days:IMC-A12: 20 mg/kg IV over 90 min on day 1 Temsirolimus (CCI-779): 20 mg IV over 30 min on day 1 Fluorine-18 2-Fluoro-2-deoxy-D-Glucose (18F-FDG): 10 mCi IVB at baseline, within 1 week of the 1st txt, 12 weeks, 24 weeks, and end of study	Total of all reporting groups
Overall Participants	6	5	5	16
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	2 40%	2 40%	4 25%
>=65 years	6 100%	3 60%	3 60%	12 75%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	6 100%	5 100%	5 100%	16 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 20%	0 0%	1 6.3%
White	6 100%	4 80%	5 100%	15 93.8%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%	5 100%	5 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	cTTP
Description	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.
Time Frame	Up to 4 weeks after completion of study treatment

Outcome Measure Data

Analysis Population Description

All patients had withdrawn from study prior to data analysis. This Outcome Measure is related to the Phase II portion of the Trial, which did not occur. Therefore, there is no data to report.

Arm/Group Title	IMC-A12: 6 mg/kg Temsirolimus 20 mg	IMC-A12: 6 mg/kg Temsirolimus 25 mg	IMC-A12: 20 mg/kg Temsirolimus 20 mg
Arm/Group Description	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Arm -1 (Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 20 mg IV over 30 min weekly)	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 25 mg IV over 30 min weekly	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=21 days:IMC-A12: 20 mg/kg IV over 90 min on day 1 Temsirolimus (CCI-779): 20 mg IV over 30 min on day 1 Fluorine-18 2-Fluoro-2-deoxy-D-Glucose (18F-FDG): 10 mCi IVB at baseline, within 1 week of the 1st txt, 12 weeks, 24 weeks, and end of study
Measure Participants	0	0	0

2. Primary Outcome

Title	Tumor Response Rate
Description	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.
Time Frame	Up to 4 weeks after completion of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IMC-A12: 6 mg/kg Temsirolimus 20 mg	IMC-A12: 6 mg/kg Temsirolimus 25 mg	IMC-A12: 20 mg/kg Temsirolimus 20 mg
Arm/Group Description	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Arm -1 (Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 20 mg IV over 30 min weekly)	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 25 mg IV over 30 min weekly	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=21 days:IMC-A12: 20 mg/kg IV over 90 min on day 1 Temsirolimus (CCI-779): 20 mg IV over 30 min on day 1 Fluorine-18 2-Fluoro-2-deoxy-D-Glucose (18F-FDG): 10 mCi IVB at baseline, within 1 week of the 1st txt, 12 weeks, 24 weeks, and end of study
Measure Participants	6	5	5
Stable Disease	2 33.3%	4 80%	1 20%
Progression of Disease	4 66.7%	1 20%	4 80%

3. Secondary Outcome

Title	Change in PSA Doubling Time
Description	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.
Time Frame	Week 1, Week 5, Week 9, Week 13, Week 17, Week 21 and Week 25

Outcome Measure Data

Analysis Population Description

Outcome not calculated. PSA decline from baseline and imaging response (at twelve weeks) instead which are recognized PCWG3 endpoints for metastatic castration resistant disease was the outcome.

Arm/Group Title	IMC-A12: 6 mg/kg Temsirolimus 20 mg	IMC-A12: 6 mg/kg Temsirolimus 25 mg	IMC-A12: 20 mg/kg Temsirolimus 20 mg
Arm/Group Description	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Arm -1 (Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 20 mg IV over 30 min weekly)	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 25 mg IV over 30 min weekly	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=21 days:IMC-A12: 20 mg/kg IV over 90 min on day 1 Temsirolimus (CCI-779): 20 mg IV over 30 min on day 1 Fluorine-18 2-Fluoro-2-deoxy-D-Glucose (18F-FDG): 10 mCi IVB at baseline, within 1 week of the 1st txt, 12 weeks, 24 weeks, and end of study
Measure Participants	0	0	0

4. Secondary Outcome

Title	Duration of Effect
Description	Summarized using descriptive statistics.
Time Frame	From the time of first dose until the time of progression, assessed up to 4 weeks after completion of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IMC-A12: 6 mg/kg Temsirolimus 20 mg	IMC-A12: 6 mg/kg Temsirolimus 25 mg	IMC-A12: 20 mg/kg Temsirolimus 20 mg
Arm/Group Description	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Arm -1 (Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 20 mg IV over 30 min weekly)	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 25 mg IV over 30 min weekly	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=21 days:IMC-A12: 20 mg/kg IV over 90 min on day 1 Temsirolimus (CCI-779): 20 mg IV over 30 min on day 1 Fluorine-18 2-Fluoro-2-deoxy-D-Glucose (18F-FDG): 10 mCi IVB at baseline, within 1 week of the 1st txt, 12 weeks, 24 weeks, and end of study
Measure Participants	6	5	5
Median (95% Confidence Interval) [weeks]	35	17.5	16

5. Secondary Outcome

Title	Maximal Percentage Change in Serum PSA as Compared to Week 12 Versus Baseline
Description	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])
Time Frame	From baseline to week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IMC-A12: 6 mg/kg Temsirolimus 20 mg	IMC-A12: 6 mg/kg Temsirolimus 25 mg	IMC-A12: 20 mg/kg Temsirolimus 20 mg
Arm/Group Description	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Arm -1 (Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 20 mg IV over 30 min weekly)	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 25 mg IV over 30 min weekly	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=21 days:IMC-A12: 20 mg/kg IV over 90 min on day 1 Temsirolimus (CCI-779): 20 mg IV over 30 min on day 1 Fluorine-18 2-Fluoro-2-deoxy-D-Glucose (18F-FDG): 10 mCi IVB at baseline, within 1 week of the 1st txt, 12 weeks, 24 weeks, and end of study
Measure Participants	6	5	5
Median (95% Confidence Interval) [percentage change in Serum PSA]	8	-1	203

6. Secondary Outcome

Title	Progression-free Survival
Description	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.
Time Frame	From the time of first dose until objective tumor progression or death, assessed up to 4 weeks after completion of study treatment

Outcome Measure Data

Analysis Population Description

All patients had withdrawn from study prior to data analysis.

Arm/Group Title	IMC-A12: 6 mg/kg Temsirolimus 20 mg	IMC-A12: 6 mg/kg Temsirolimus 25 mg	Arm 1A
Arm/Group Description	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Arm -1 (Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 20 mg IV over 30 min weekly)	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 25 mg IV over 30 min weekly	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=21 days:IMC-A12: 20 mg/kg IV over 90 min on day 1 Temsirolimus (CCI-779): 20 mg IV over 30 min on day 1 Fluorine-18 2-Fluoro-2-deoxy-D-Glucose (18F-FDG): 10 mCi IVB at baseline, within 1 week of the 1st txt, 12 weeks, 24 weeks, and end of study
Measure Participants	0	0	0

7. Secondary Outcome

Title	Rate of Adverse Events According to NCI CTCAE Version 4.0
Description	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.
Time Frame	Up to 4 weeks after completion of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IMC-A12: 6 mg/kg Temsirolimus 20 mg	IMC-A12: 6 mg/kg Temsirolimus 25 mg	IMC-A12: 20 mg/kg Temsirolimus 20 mg
Arm/Group Description	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Arm -1 (Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 20 mg IV over 30 min weekly)	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 25 mg IV over 30 min weekly	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=21 days:IMC-A12: 20 mg/kg IV over 90 min on day 1 Temsirolimus (CCI-779): 20 mg IV over 30 min on day 1 Fluorine-18 2-Fluoro-2-deoxy-D-Glucose (18F-FDG): 10 mCi IVB at baseline, within 1 week of the 1st txt, 12 weeks, 24 weeks, and end of study
Measure Participants	6	5	5
Number [percentage of participants affected]	100 1666.7%	100 2000%	60 1200%

Adverse Events

Arm/Group Title	IMC-A12: 6mg/kg Temsirolimus 20 mg		IMC-A12: 6 mg/kg Temsirolimus 25 mg		IMC-A12: 20 mg/kg Temsirolimus 20 mg
Arm/Group Description	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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Arm -1 (Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 20 mg IV over 30 min weekly)		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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=28 days, IMC-A12: 6 mg/kg IV over 60 min weekly, Temsirolimus (CCI-779): 25 mg IV over 30 min weekly		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. Cixutumumab: Given IV Diagnostic Laboratory Biomarker Analysis: Correlative studies Temsirolimus: Given IV Cycle=21 days:IMC-A12: 20 mg/kg IV over 90 min on day 1 Temsirolimus (CCI-779): 20 mg IV over 30 min on day 1 Fluorine-18 2-Fluoro-2-deoxy-D-Glucose (18F-FDG): 10 mCi IVB at baseline, within 1 week of the 1st txt, 12 weeks, 24 weeks, and end of study
All Cause Mortality
	IMC-A12: 6mg/kg Temsirolimus 20 mg		IMC-A12: 6 mg/kg Temsirolimus 25 mg		IMC-A12: 20 mg/kg Temsirolimus 20 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	IMC-A12: 6mg/kg Temsirolimus 20 mg		IMC-A12: 6 mg/kg Temsirolimus 25 mg		IMC-A12: 20 mg/kg Temsirolimus 20 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/6 (50%)		1/5 (20%)		1/5 (20%)
Eye disorders
Optic nerve disorder	0/6 (0%)	0	0/5 (0%)	0	1/5 (20%)	2
Investigations
Lipase increased	2/6 (33.3%)	2	0/5 (0%)	0	0/5 (0%)	0
Serum amylase increased	0/6 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Metabolism and nutrition disorders
Hyponatremia	1/6 (16.7%)	1	0/5 (0%)	0	0/5 (0%)	0
Nervous system disorders
Dizziness	1/6 (16.7%)	1	0/5 (0%)	0	0/5 (0%)	0
Psychiatric disorders
Confusion	1/6 (16.7%)	1	0/5 (0%)	0	0/5 (0%)	0
Vascular disorders
Hypertension	1/6 (16.7%)	1	0/5 (0%)	0	0/5 (0%)	0
Other (Not Including Serious) Adverse Events
	IMC-A12: 6mg/kg Temsirolimus 20 mg		IMC-A12: 6 mg/kg Temsirolimus 25 mg		IMC-A12: 20 mg/kg Temsirolimus 20 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		5/5 (100%)		3/5 (60%)
Gastrointestinal disorders
Constipation	0/6 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Mucositis oral	1/6 (16.7%)	1	3/5 (60%)	5	0/5 (0%)	0
Nausea	0/6 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Rectal pain	0/6 (0%)	0	1/5 (20%)	2	0/5 (0%)	0
General disorders
Fatigue	2/6 (33.3%)	2	2/5 (40%)	3	1/5 (20%)	1
Infections and infestations
Skin infection	1/6 (16.7%)	1	0/5 (0%)	0	0/5 (0%)	0
Tooth infection	1/6 (16.7%)	2	0/5 (0%)	0	0/5 (0%)	0
Investigations
Alkaline phosphatase increased	1/6 (16.7%)	2	1/5 (20%)	6	0/5 (0%)	0
Alanine aminotransferase increased	0/6 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Cholesterol high	0/6 (0%)	0	2/5 (40%)	2	0/5 (0%)	0
Neutrophil count decreased	0/6 (0%)	0	1/5 (20%)	7	0/5 (0%)	0
Platelet count decreased	1/6 (16.7%)	3	0/5 (0%)	0	0/5 (0%)	0
Serum amylase increased	1/6 (16.7%)	1	0/5 (0%)	0	0/5 (0%)	0
Weight loss	1/6 (16.7%)	1	1/5 (20%)	1	0/5 (0%)	0
White blood cell decreased	1/6 (16.7%)	1	1/5 (20%)	1	0/5 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	4/6 (66.7%)	36	3/5 (60%)	35	1/5 (20%)	3
Hypertriglyceridemia	2/6 (33.3%)	6	2/5 (40%)	4	2/5 (40%)	2
Hypophosphatemia	1/6 (16.7%)	1	0/5 (0%)	0	0/5 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	1/6 (16.7%)	1	0/5 (0%)	0	0/5 (0%)	0
Neck pain	0/6 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Nervous system disorders
Headache	0/6 (0%)	0	1/5 (20%)	2	0/5 (0%)	0
Peripheral motor neuropathy	1/6 (16.7%)	1	0/5 (0%)	0	0/5 (0%)	0
Peripheral sensory neuropathy	0/6 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Psychiatric disorders
Depression	1/6 (16.7%)	1	0/5 (0%)	0	0/5 (0%)	0
Psychiatric disorders - Other, specify	0/6 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Renal and urinary disorders
Renal and urinary disorders - Other, specify	1/6 (16.7%)	1	0/5 (0%)	0	0/5 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/6 (16.7%)	1	1/5 (20%)	1	0/5 (0%)	0
Epistaxis	1/6 (16.7%)	1	0/5 (0%)	0	0/5 (0%)	0
Pneumonitis	1/6 (16.7%)	1	2/5 (40%)	2	0/5 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	1/6 (16.7%)	1	0/5 (0%)	0	0/5 (0%)	0
Vascular disorders
Thromboembolic event	1/6 (16.7%)	1	0/5 (0%)	0	0/5 (0%)	0

Limitations/Caveats

cTTP This Outcome Measure is related to the Phase II portion of the Trial, which did not occur. All patients had withdrawn from study prior to data analysis. Therefore, there is no data to report for this measure.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.