Skip to content

Bicalutamide and Goserelin or Leuprolide Acetate With or Without Cixutumumab in Treating Patients With Newly Diagnosed Metastatic Prostate Cancer

A Randomized Phase II Study of Androgen Deprivation Combined With IMC-A12 Versus Androgen Deprivation Alone for Patients With New Hormone Sensitive Metastatic Prostate Cancer

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01120236
Enrollment
211
Registered
2010-05-10
Start date
2010-12-31
Completion date
2017-08-23
Last updated
2018-02-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Prostate Adenocarcinoma, Recurrent Prostate Carcinoma, Stage IV Prostate Cancer

Brief summary

This randomized phase II trial is studying bicalutamide, goserelin, or leuprolide acetate to see how well they work when given with or without cixutumumab in treating patients with newly diagnosed metastatic prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, goserelin, or leuprolide acetate, may lessen the amount of androgens made by the body. 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. It is not yet known whether bicalutamide, goserelin, or leuprolide acetate are more effective when given with or without cixutumumab in treating prostate cancer.

Detailed description

PRIMARY OBJECTIVES: I. To compare the undetectable prostate-specific antigen (PSA) rate (PSA \< 0.2 ng/mL) after seven cycles (28 weeks) of protocol treatment between those randomized to a luteinizing hormone-releasing hormone (LHRH) agonist and bicalutamide and those randomized to a LHRH agonist, bicalutamide and IMC-A12 (cixutumumab). SECONDARY OBJECTIVES: I. To assess the safety and tolerability of the combination of IMC-A12 with a LHRH agonist and bicalutamide. II. To compare the proportion of men who do not achieve a PSA of \< 4 ng/mL between the two groups. III. To assess the accuracy of the prognostic model of undetectable PSA that was developed from Southwest Oncology Group (SWOG)-9346 using current trial data from each arm. IV. To assess serum samples and peripheral blood mononuclear cells (PBMNC) for pharmacodynamic activity with potential biomarkers for IMC-A12 (including, but not limited to: insulin-like growth factor \[IGF\]-I, free IGF-I, IGF-II, IGF binding protein \[IGFBP\]2, IGFBP3, growth hormone, insulin and C-peptide) obtained from optional blood specimens both before initiation of androgen deprivation therapy and twelve weeks after initiation of combined therapy. V. To determine baseline pre-treatment circulating tumor cell (CTC) quantities and response to therapy (for those patients with detectable CTC levels \>= 1) twelve weeks later. VI. In the same subset of patients where CTC levels are obtained, determine baseline serum levels of micro-ribonucleic acids (RNAs) to include but not limited to microRNA (mi)-141 both before initiation of androgen deprivation therapy and twelve weeks after combined therapy. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive androgen deprivation therapy comprising bicalutamide orally (PO) once daily (QD) on days 1-28 and either goserelin acetate subcutaneously (SC) or leuprolide acetate intramuscularly (IM) every 1, 3, 4, 6, or 12 months. Patients also receive cixutumumab intravenously (IV) over 1 hour on days 1 and 15. Treatment repeats every 28 days for 7 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I. After completion of study treatment, patients are followed up every 6 months for 2 years and then annually for 3 years.

Interventions

DRUGBicalutamide

Given PO

BIOLOGICALCixutumumab

Given IV

DRUGGoserelin Acetate

Given SC

OTHERLaboratory Biomarker Analysis

Correlative studies

DRUGLeuprolide Acetate

Given IM

OTHERPharmacological Study

Correlative studies

Sponsors

National Cancer Institute (NCI)
Lead SponsorNIH

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* All patients must have a histologically or cytologically proven diagnosis of adenocarcinoma of the prostate; note: If there is no formal biopsy report documenting the diagnosis of prostate cancer, the patient can be allowed on trial if the PSA level is at least 20, and there are at least three definitive metastatic lesions seen on scan; all patients must have had metastatic (M1) disease as evidenced by soft tissue and/or bony metastases prior to androgen deprivation therapy initiation; patients must have at least one of the following at the time they started androgen deprivation therapy: * Visceral disease (liver, lung, or other viscera) * Bone metastases to sites in either the axial (spine, pelvis, ribs, or skull) and/or the appendicular (clavicle, humerus, or femur) skeleton * Lymph node disease not considered to be encompassed within a single radiotherapy port (e.g., above the aortic bifurcation, etc.) * Patients who have measurable disease must have radiographic assessment (at least an abdominal/pelvic computed tomography \[CT\]) within 28 days prior to registration; non-measurable disease must also be assessed (e.g., bone scan) in all patients within 56 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form * Patients must have a PSA \>= 5 ng/mL obtained within 90 days prior to initiation of androgen deprivation therapy * Patients with known brain metastases are not eligible; brain imaging studies are not required for eligibility if the patient has no neurologic signs or symptoms, but if brain imaging studies are performed, they must be negative for disease * Patient must have had no more than 30 days of prior medical castration for metastatic prostate cancer (prior androgen deprivation therapy is allowed if it was received with curative intent in the neoadjuvant, concurrent, and/or adjuvant fashion and at least 2 years have elapsed since completion of androgen deprivation therapy); the start date of medical castration is considered the day the patient first received an injection of a LHRH agonist, not an oral antiandrogen; if the method of castration is luteinizing hormone releasing hormone (LHRH) agonists (i.e., leuprolide or goserelin), the patient must be willing to continue the use of LHRH agonists and add bicalutamide for combined androgen deprivation therapy (ADT) during protocol treatment; the 30 day window begins from the date of receiving the LHRH agonist, not the oral antiandrogen; if the patient was on a different antiandrogen (e.g. flutamide), the patient must be willing to switch over to bicalutamide; patients must not have received bilateral orchiectomy; patients must not have received or be planning to receive LHRH antagonists (i.e., Degarelix); however, if the patient was initiated on a LHRH antagonist within the 30 day window and is willing to switch to a LHRH agonist with bicalutamide, he may enroll on the late induction group * Patients who have not already started androgen deprivation therapy must be offered the opportunity to participate in the translational medicine studies; once a patient has started any form of antiandrogen (i.e., either bicalutamide or LHRH agonist), he is not eligible for any translational medicine studies * Patients must not have received any prior cytotoxic chemotherapy for metastatic prostate cancer; prior cytotoxic chemotherapy with curative intent in the neoadjuvant or adjuvant setting is allowed; patients must not have received any prior treatment with agents that directly inhibit IGF or IGFRs * Patients must not have received prior strontium-89, rhenium-186, rhenium-188, or samarium-153 radionuclide therapy within 28 days prior to registration * Patients may have received prior radiation therapy or biologic therapy (e.g. vaccines, immunotherapy, anti-sense, small molecules, monoclonal antibodies); however, at least 28 days must have elapsed since completion of therapy and patient must have recovered from all side effects * Patients may have received prior surgery; for all major surgeries, at least 28 days must have elapsed since completion and patient must have recovered from all side effects * Leukocytes \>= 3,000 mcL * Absolute neutrophil count (ANC) \>= 1,500 mcL * Hemoglobin \>= 9 g/dL * Platelets \>= 100,000/mcL * Bilirubin =\< 1.5 times the institutional upper limit of normal (ULN) (unless documented Gilbert's disease) * Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 3 times the institutional ULN, or =\< 5 times the institutional ULN if liver metastases are present * Creatinine =\< 2.0 x the institutional ULN or calculated creatinine clearance \>= 40 mL/min * International normalized ratio (INR) =\< 1.5 * Partial thromboplastin time (PTT) no more than 5 seconds above the institutional ULN * Patients receiving prophylactic low dose coumadin or low molecular weight heparin are eligible as long as they meet these coagulation criteria; patients requiring full-dose (therapeutic) anticoagulation are eligible provided that they have been on a stable dose of anticoagulation and the coagulation parameters are stable within the therapeutic range (e.g., INR 2-3 for patients on therapeutic warfarin) * Patients must have a hemoglobin A1c (HgA1c) =\< 7% AND fasting glucose of \< 160 mg/dL or below the institutional ULN within 14 days prior to registration; patients with diabetes mellitus who meet this criterion must be on a stable dietary or therapeutic regimen for this condition * Patients must not have a history of symptomatic congestive heart failure or a known ejection fraction (left ventricular ejection fraction \[LVEF\]) that is \>= 10% below the lower limit of normal (LLN); if left ventricular (LV) dysfunction is suspected, but not confirmed by review of past medical history, a multi gated acquisition scan (MUGA) or echocardiogram must be obtained within 90 days prior to registration * Patient must not have a history of allergic reaction attributed to compounds of similar chemical or biologic composition to IMC-A12; patients must not have received prior chimerized or murine monoclonal antibody therapy * Patients must have a Zubrod performance status of 0 - 2; Zubrod performance status 3 will be allowed if from bone pain only * Patients with human immunodeficiency virus (HIV) positivity requiring antiretroviral therapy are not eligible for this study * Patients must have no plans to receive concurrent chemotherapy, hormonal therapy (other than the LHRH agonist and oral anti-androgen), radiotherapy, immunotherapy or any other type of therapy for treatment of cancer while on this protocol treatment; concurrent bone targeting agents that do not have effect on PSA (i.e. denosumab or zoledronic acid) are allowed * Patients must have no plans to receive concurrent five-alpha reductase inhibitors (e.g. finasteride and dutasteride), ketoconazole, diethylstilbestrol/DES, or other estrogen-based therapy while on this protocol treatment * No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years * Men of reproductive potential must have agreed to use an effective contraceptive method while receiving treatment on this study and for at least three months after protocol treatment ends * All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines * As part of the OPEN registration process, the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Design outcomes

Primary

MeasureTime frameDescription
Undetectable PSA Rate7 monthsUndetectable PSA rate (\<= 0.2 ng/mL) after seven cycles (28 weeks) of protocol treatment

Secondary

MeasureTime frameDescription
Proportion of Patients Who do Not Achieve a Partial PSA ResponseUp to 5 yearsA partial PSA response is considered \<= 4 ng/mL
Accuracy of the Prognostic Model of Undetectable PSA (Developed From SWOG-9346)Up to 5 yearsThe logistic regression algorithm for predicting undetectable PSA that was developed for SWOG-9346 using its baseline risk factors (age at registration, performance status, baseline PSA, and bone pain) will be applied to each arm of this trial to evaluate the level of agreement between the observed and predicted undetectable PSA rates.
Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) CountsBaselineThe Friedman test will be used to evaluate correlations between microRNA measures (CT) and Baseline CTCs.
Change in Level of CTCsBaseline to 28 weeksWill be correlated with 28-week PSA response.
Correlation of microRNA Measures With 28-week PSA ResponseBaseline to 28 weeksThe Friedman test will be used to evaluate correlations between microRNA measures (CT) and 28-week PSA response.
ToxicityUp to 28 weeksOnly adverse events that are possibly, probably or definitely related to study drug are reported.

Other

MeasureTime frameDescription
Change in Level of InsulinBaseline to 12 weeksSerum samples and peripheral blood mononuclear cells (PBMNC) for pharmacodynamic activity with potential biomarkers for IMC-A12 (insulin) obtained from optional blood specimens both before initiation of androgen deprivation therapy and twelve weeks after initiation of combined therapy. Results are reported as the difference between baseline and 12 weeks after start of therapy.
Change in Level of IGF-I, Free IGF-I and C-peptideBaseline to 12 weeksSerum samples and peripheral blood mononuclear cells (PBMNC) for pharmacodynamic activity with potential biomarkers for IMC-A12 (including, but not limited to: IGF-I, free IGF-I and C-peptide) obtained from optional blood specimens both before initiation of androgen deprivation therapy and twelve weeks after initiation of combined therapy. Results are reported as the difference between baseline and 12 weeks after start of therapy.
Change in Level of IGFBP2, IGFBP3 and Growth HormoneBaseline to 12 weeksSerum samples and peripheral blood mononuclear cells (PBMNC) for pharmacodynamic activity with potential biomarkers for IMC-A12 (including, but not limited to: IGFBP2, IGFBP3 and Growth Hormone) obtained from optional blood specimens both before initiation of androgen deprivation therapy and twelve weeks after initiation of combined therapy. Results are reported as the difference between baseline and 12 weeks after start of therapy.

Countries

Canada, United States

Participant flow

Participants by arm

ArmCount
Arm I (Androgen Deprivation and Cixutumumab)
Patients receive androgen deprivation therapy comprising bicalutamide PO QD on days 1-28 and either goserelin acetate SC or leuprolide acetate IM every 1, 3, 4, 6, or 12 months. Patients also receive cixutumumab IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for 7 courses in the absence of disease progression or unacceptable toxicity. Bicalutamide: Given PO Cixutumumab: Given IV Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies
105
Arm II (Androgen Deprivation Therapy)
Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies
105
Total210

Baseline characteristics

CharacteristicTotalArm I (Androgen Deprivation and Cixutumumab)Arm II (Androgen Deprivation Therapy)
Age, Continuous66 years65 years66 years
Body Mass Index (BMI)
18.5 to 24.9 (normal weight)
50 participants21 participants29 participants
Body Mass Index (BMI)
<18.5 (underweight)
3 participants1 participants2 participants
Body Mass Index (BMI)
25 to 29.9 (overweight)
75 participants36 participants39 participants
Body Mass Index (BMI)
>= 30 (obese)
76 participants43 participants33 participants
Body Mass Index (BMI)
Unknown
6 participants4 participants2 participants
Bone Pain63 participants28 participants35 participants
Early Induction Androgen Deprivation124 participants59 participants65 participants
Gleason Score
7
40 participants29 participants11 participants
Gleason Score
<7
14 participants8 participants6 participants
Gleason Score
>=7
145 participants63 participants82 participants
Gleason Score
Unknown
11 participants5 participants6 participants
Prostate-Specific Antigen (PSA)34 ng/mL31 ng/mL37 ng/mL
Race/Ethnicity, Customized
Black
14 participants4 participants10 participants
Race/Ethnicity, Customized
Other
14 participants7 participants7 participants
Race/Ethnicity, Customized
White
182 participants94 participants88 participants
Region of Enrollment
United States
210 participants105 participants105 participants
Sex: Female, Male
Female
0 Participants0 Participants0 Participants
Sex: Female, Male
Male
210 Participants105 Participants105 Participants
Site of Metastasis
Bone Only
119 participants56 participants63 participants
Site of Metastasis
Lymph Node and Bone
36 participants19 participants17 participants
Site of Metastasis
Lymph Node Only
24 participants15 participants9 participants
Site of Metastasis
Visceral
31 participants15 participants16 participants
Weight88 kg90 kg86 kg
Zubrod Performance Score
0
127 participants62 participants65 participants
Zubrod Performance Score
1
79 participants41 participants38 participants
Zubrod Performance Score
2
4 participants2 participants2 participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
101 / 10194 / 104
serious
Total, serious adverse events
10 / 1014 / 104

Outcome results

Primary

Undetectable PSA Rate

Undetectable PSA rate (\<= 0.2 ng/mL) after seven cycles (28 weeks) of protocol treatment

Time frame: 7 months

Population: One patient from Arm II (androgen deprivation therapy) was ineligible because of lack of a demonstrable radiographic metastasis. This patient was excluded from analyses.

ArmMeasureValue (NUMBER)
Arm I (Androgen Deprivation and Cixutumumab)Undetectable PSA Rate42 participants
Arm II (Androgen Deprivation Therapy)Undetectable PSA Rate34 participants
Comparison: An intention-to-treat approach was used in analysis of the primary endpoint. A 45% undetectable PSA \<= 0.2 ng/mL rate at 28 weeks was assumed for (control) arm II , based on data from SWOG 9346. Using a one-sided type I error rate of 0.10, we had 90% statistical power to detect an absolute difference of 20% in the undetectable PSA rate with the addition of cixutumumab using Fisher's exact test.p-value: 0.16Fisher Exact
Secondary

Accuracy of the Prognostic Model of Undetectable PSA (Developed From SWOG-9346)

The logistic regression algorithm for predicting undetectable PSA that was developed for SWOG-9346 using its baseline risk factors (age at registration, performance status, baseline PSA, and bone pain) will be applied to each arm of this trial to evaluate the level of agreement between the observed and predicted undetectable PSA rates.

Time frame: Up to 5 years

Population: The data from this trial was intended to be used as a validation dataset for the prognostic model built using data from SWOG-9346. However, data for this objective was not collected.

Secondary

Change in Level of CTCs

Will be correlated with 28-week PSA response.

Time frame: Baseline to 28 weeks

Population: Among the 50 patients in this biomarker substudy, 1 was ineligible for the trial, 6 started LHRH therapy prior to registration, and 4 had CTC blood samples that were not assay evaluable. The remaining 39 patients were included in this analysis.

ArmMeasureCategoryValue (COUNT_OF_PARTICIPANTS)
Arm I (Androgen Deprivation and Cixutumumab)Change in Level of CTCs0.2 < PSA <=4.0 ng/mL0 Participants
Arm I (Androgen Deprivation and Cixutumumab)Change in Level of CTCsPSA <= 0.2 ng/mL12 Participants
Arm I (Androgen Deprivation and Cixutumumab)Change in Level of CTCsPSA > 4.0 ng/mL4 Participants
Arm II (Androgen Deprivation Therapy)Change in Level of CTCs0.2 < PSA <=4.0 ng/mL2 Participants
Arm II (Androgen Deprivation Therapy)Change in Level of CTCsPSA <= 0.2 ng/mL5 Participants
Arm II (Androgen Deprivation Therapy)Change in Level of CTCsPSA > 4.0 ng/mL2 Participants
PSA Non-RespondersChange in Level of CTCsPSA <= 0.2 ng/mL4 Participants
PSA Non-RespondersChange in Level of CTCsPSA > 4.0 ng/mL7 Participants
PSA Non-RespondersChange in Level of CTCs0.2 < PSA <=4.0 ng/mL3 Participants
Secondary

Correlation of microRNA Measures With 28-week PSA Response

The Friedman test will be used to evaluate correlations between microRNA measures (CT) and 28-week PSA response.

Time frame: Baseline to 28 weeks

Population: Among the 50 patients in this biomarker substudy, 10 patients were excluded: 1 ineligible for S0925, 6 started LHRH therapy prior to registration, 3 had insufficient miRNA samples. The remaining 40 patienets were included in this analysis.

ArmMeasureGroupValue (MEDIAN)
Arm I (Androgen Deprivation and Cixutumumab)Correlation of microRNA Measures With 28-week PSA ResponsemiR-21032.5 Cycle Threshold (CT)
Arm I (Androgen Deprivation and Cixutumumab)Correlation of microRNA Measures With 28-week PSA ResponsemiR-200b33.6 Cycle Threshold (CT)
Arm I (Androgen Deprivation and Cixutumumab)Correlation of microRNA Measures With 28-week PSA ResponsemiR-14132.6 Cycle Threshold (CT)
Arm I (Androgen Deprivation and Cixutumumab)Correlation of microRNA Measures With 28-week PSA ResponsemiR-200a34.5 Cycle Threshold (CT)
Arm I (Androgen Deprivation and Cixutumumab)Correlation of microRNA Measures With 28-week PSA ResponsemiR-37533.0 Cycle Threshold (CT)
Arm II (Androgen Deprivation Therapy)Correlation of microRNA Measures With 28-week PSA ResponsemiR-200b33.6 Cycle Threshold (CT)
Arm II (Androgen Deprivation Therapy)Correlation of microRNA Measures With 28-week PSA ResponsemiR-14132.0 Cycle Threshold (CT)
Arm II (Androgen Deprivation Therapy)Correlation of microRNA Measures With 28-week PSA ResponsemiR-200a33.8 Cycle Threshold (CT)
Arm II (Androgen Deprivation Therapy)Correlation of microRNA Measures With 28-week PSA ResponsemiR-21032.1 Cycle Threshold (CT)
Arm II (Androgen Deprivation Therapy)Correlation of microRNA Measures With 28-week PSA ResponsemiR-37532.6 Cycle Threshold (CT)
PSA Non-RespondersCorrelation of microRNA Measures With 28-week PSA ResponsemiR-37529.5 Cycle Threshold (CT)
PSA Non-RespondersCorrelation of microRNA Measures With 28-week PSA ResponsemiR-21032.3 Cycle Threshold (CT)
PSA Non-RespondersCorrelation of microRNA Measures With 28-week PSA ResponsemiR-14131.5 Cycle Threshold (CT)
PSA Non-RespondersCorrelation of microRNA Measures With 28-week PSA ResponsemiR-200b32.6 Cycle Threshold (CT)
PSA Non-RespondersCorrelation of microRNA Measures With 28-week PSA ResponsemiR-200a33.8 Cycle Threshold (CT)
Secondary

Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) Counts

The Friedman test will be used to evaluate correlations between microRNA measures (CT) and Baseline CTCs.

Time frame: Baseline

Population: Among the 50 patients in this biomarker substudy, 14 patients were excluded: 1 ineligible for S0925, 6 started LHRH therapy prior to registration, 3 had insufficient miRNA samples and 4 had insufficient CTC samples. The remaining 36 patients were used in this analysis.

ArmMeasureGroupValue (MEDIAN)
Arm I (Androgen Deprivation and Cixutumumab)Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) CountsmiR-21032.5 Cycle Threshold (CT)
Arm I (Androgen Deprivation and Cixutumumab)Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) CountsmiR-200b33.4 Cycle Threshold (CT)
Arm I (Androgen Deprivation and Cixutumumab)Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) CountsmiR-14133.0 Cycle Threshold (CT)
Arm I (Androgen Deprivation and Cixutumumab)Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) CountsmiR-200a34.4 Cycle Threshold (CT)
Arm I (Androgen Deprivation and Cixutumumab)Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) CountsmiR-37532.8 Cycle Threshold (CT)
Arm II (Androgen Deprivation Therapy)Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) CountsmiR-200b33.2 Cycle Threshold (CT)
Arm II (Androgen Deprivation Therapy)Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) CountsmiR-14132.7 Cycle Threshold (CT)
Arm II (Androgen Deprivation Therapy)Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) CountsmiR-200a34.7 Cycle Threshold (CT)
Arm II (Androgen Deprivation Therapy)Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) CountsmiR-21032.7 Cycle Threshold (CT)
Arm II (Androgen Deprivation Therapy)Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) CountsmiR-37532.7 Cycle Threshold (CT)
PSA Non-RespondersCorrelation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) CountsmiR-37530.2 Cycle Threshold (CT)
PSA Non-RespondersCorrelation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) CountsmiR-21032.1 Cycle Threshold (CT)
PSA Non-RespondersCorrelation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) CountsmiR-14131.9 Cycle Threshold (CT)
PSA Non-RespondersCorrelation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) CountsmiR-200b33.6 Cycle Threshold (CT)
PSA Non-RespondersCorrelation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) CountsmiR-200a33.0 Cycle Threshold (CT)
Secondary

Proportion of Patients Who do Not Achieve a Partial PSA Response

A partial PSA response is considered \<= 4 ng/mL

Time frame: Up to 5 years

Population: One patient from Arm II (androgen deprivation therapy) was ineligible because of lack of a demonstrable radiographic metastasis. This patient was excluded from analyses.

ArmMeasureValue (NUMBER)
Arm I (Androgen Deprivation and Cixutumumab)Proportion of Patients Who do Not Achieve a Partial PSA Response46 participants
Arm II (Androgen Deprivation Therapy)Proportion of Patients Who do Not Achieve a Partial PSA Response56 participants
Comparison: Proportion of patients in each arm with PSA \> 4 ng/mL after seven cycles of protocol treatment were compared.p-value: 0.11Fisher Exact
Secondary

Toxicity

Only adverse events that are possibly, probably or definitely related to study drug are reported.

Time frame: Up to 28 weeks

Population: All participants receiving at least some protocol treatment were included in toxicity analysis. Four patients on Arm I (androgen deprivation and cixutumumab) and two patients on Arm II (androgen deprivation therapy) did not receive any protocol treatment and were therefore excluded from this analysis.

ArmMeasureGroupValue (NUMBER)
Arm I (Androgen Deprivation and Cixutumumab)ToxicityDepression0 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityCognitive disturbance1 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityAlanine aminotransferase increased1 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityAnemia1 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityAnxiety0 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityAspartate aminotransferase increased1 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityErectile dysfunction1 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityExostosis1 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityGlucose intolerance0 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityHot flashes1 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityHypercalcemia2 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityHyperglycemia8 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityHypertension2 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityHypertriglyceridemia1 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityLeft ventricular systolic dysfunction1 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityNausea1 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityObesity1 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicitySoft tissue infection1 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityUrinary tract infection1 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityUrinary tract obstruction0 Participants
Arm I (Androgen Deprivation and Cixutumumab)ToxicityVomiting1 Participants
Arm II (Androgen Deprivation Therapy)ToxicityHypercalcemia0 Participants
Arm II (Androgen Deprivation Therapy)ToxicityAspartate aminotransferase increased0 Participants
Arm II (Androgen Deprivation Therapy)ToxicityUrinary tract infection0 Participants
Arm II (Androgen Deprivation Therapy)ToxicityCognitive disturbance0 Participants
Arm II (Androgen Deprivation Therapy)ToxicityAnxiety1 Participants
Arm II (Androgen Deprivation Therapy)ToxicityHyperglycemia0 Participants
Arm II (Androgen Deprivation Therapy)ToxicityAlanine aminotransferase increased0 Participants
Arm II (Androgen Deprivation Therapy)ToxicityObesity1 Participants
Arm II (Androgen Deprivation Therapy)ToxicityAnemia1 Participants
Arm II (Androgen Deprivation Therapy)ToxicityHypertension2 Participants
Arm II (Androgen Deprivation Therapy)ToxicityVomiting0 Participants
Arm II (Androgen Deprivation Therapy)ToxicityDepression1 Participants
Arm II (Androgen Deprivation Therapy)ToxicityHypertriglyceridemia0 Participants
Arm II (Androgen Deprivation Therapy)ToxicityErectile dysfunction0 Participants
Arm II (Androgen Deprivation Therapy)ToxicitySoft tissue infection0 Participants
Arm II (Androgen Deprivation Therapy)ToxicityExostosis0 Participants
Arm II (Androgen Deprivation Therapy)ToxicityLeft ventricular systolic dysfunction0 Participants
Arm II (Androgen Deprivation Therapy)ToxicityGlucose intolerance1 Participants
Arm II (Androgen Deprivation Therapy)ToxicityUrinary tract obstruction1 Participants
Arm II (Androgen Deprivation Therapy)ToxicityHot flashes1 Participants
Arm II (Androgen Deprivation Therapy)ToxicityNausea0 Participants
Other Pre-specified

Change in Level of IGFBP2, IGFBP3 and Growth Hormone

Serum samples and peripheral blood mononuclear cells (PBMNC) for pharmacodynamic activity with potential biomarkers for IMC-A12 (including, but not limited to: IGFBP2, IGFBP3 and Growth Hormone) obtained from optional blood specimens both before initiation of androgen deprivation therapy and twelve weeks after initiation of combined therapy. Results are reported as the difference between baseline and 12 weeks after start of therapy.

Time frame: Baseline to 12 weeks

ArmMeasureGroupValue (MEAN)Dispersion
Arm I (Androgen Deprivation and Cixutumumab)Change in Level of IGFBP2, IGFBP3 and Growth HormoneIGFBP-I-946 pg/mLStandard Deviation 2309.3
Arm I (Androgen Deprivation and Cixutumumab)Change in Level of IGFBP2, IGFBP3 and Growth HormoneIGFBP-III13893 pg/mLStandard Deviation 47335.2
Arm I (Androgen Deprivation and Cixutumumab)Change in Level of IGFBP2, IGFBP3 and Growth HormoneGH66 pg/mLStandard Deviation 159.9
Arm II (Androgen Deprivation Therapy)Change in Level of IGFBP2, IGFBP3 and Growth HormoneIGFBP-I-904 pg/mLStandard Deviation 32362.4
Arm II (Androgen Deprivation Therapy)Change in Level of IGFBP2, IGFBP3 and Growth HormoneIGFBP-III291 pg/mLStandard Deviation 13344.5
Arm II (Androgen Deprivation Therapy)Change in Level of IGFBP2, IGFBP3 and Growth HormoneGH-25 pg/mLStandard Deviation 327.8
Other Pre-specified

Change in Level of IGF-I, Free IGF-I and C-peptide

Serum samples and peripheral blood mononuclear cells (PBMNC) for pharmacodynamic activity with potential biomarkers for IMC-A12 (including, but not limited to: IGF-I, free IGF-I and C-peptide) obtained from optional blood specimens both before initiation of androgen deprivation therapy and twelve weeks after initiation of combined therapy. Results are reported as the difference between baseline and 12 weeks after start of therapy.

Time frame: Baseline to 12 weeks

ArmMeasureGroupValue (MEAN)Dispersion
Arm I (Androgen Deprivation and Cixutumumab)Change in Level of IGF-I, Free IGF-I and C-peptideC-peptide-7 ng/mLStandard Deviation 24.5
Arm I (Androgen Deprivation and Cixutumumab)Change in Level of IGF-I, Free IGF-I and C-peptideIGF-I0 ng/mLStandard Deviation 2.4
Arm I (Androgen Deprivation and Cixutumumab)Change in Level of IGF-I, Free IGF-I and C-peptideIGF-II10 ng/mLStandard Deviation 46.7
Arm II (Androgen Deprivation Therapy)Change in Level of IGF-I, Free IGF-I and C-peptideC-peptide3 ng/mLStandard Deviation 20.1
Arm II (Androgen Deprivation Therapy)Change in Level of IGF-I, Free IGF-I and C-peptideIGF-I1 ng/mLStandard Deviation 2.7
Arm II (Androgen Deprivation Therapy)Change in Level of IGF-I, Free IGF-I and C-peptideIGF-II-6 ng/mLStandard Deviation 43.7
Other Pre-specified

Change in Level of Insulin

Serum samples and peripheral blood mononuclear cells (PBMNC) for pharmacodynamic activity with potential biomarkers for IMC-A12 (insulin) obtained from optional blood specimens both before initiation of androgen deprivation therapy and twelve weeks after initiation of combined therapy. Results are reported as the difference between baseline and 12 weeks after start of therapy.

Time frame: Baseline to 12 weeks

ArmMeasureValue (MEAN)Dispersion
Arm I (Androgen Deprivation and Cixutumumab)Change in Level of Insulin0 ulU/mLStandard Deviation 5.1
Arm II (Androgen Deprivation Therapy)Change in Level of Insulin0 ulU/mLStandard Deviation 1.5

Source: ClinicalTrials.gov · Data processed: Mar 8, 2026