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A Study of IMC-A12 or Ramucirumab Plus Mitoxantrone and Prednisone in Prostate Cancer

Information source: Eli Lilly and Company
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Prostate Cancer

Intervention: IMC-A12 (Biological); Mitoxantrone (Drug); Prednisone (Drug); IMC-1121B (ramucirumab) (Biological)

Phase: Phase 2

Status: Completed

Sponsored by: Eli Lilly and Company

Official(s) and/or principal investigator(s):
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Study Director, Affiliation: Eli Lilly and Company

Summary

The purpose of this study is to determine whether IMC-A12 or IMC-1121B (ramucirumab) with Mitoxantrone and Prednisone is effective in the treatment of metastatic androgen- independent prostate cancer (APIC).

Clinical Details

Official title: A Phase 2, Multicenter, Randomized Study of IMC-A12 or IMC-1121B Plus Mitoxantrone and Prednisone in Metastatic Androgen-Independent Prostate Cancer (AIPC) Following Disease Progression on Docetaxel-Based Chemotherapy

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Composite Progression-free Survival (cPFS)

Secondary outcome:

Summary Listing of Participants Reporting Treatment-Emergent Adverse Events

Time to Radiographic Evidence of Disease Progression

Prostate Specific Antigen (PSA) Response Rate

Composite Progression-free Survival (cPFS) at 6-months

Composite Progression-free Survival (cPFS) at 9-months

Composite Progression-free Survival (cPFS) at 12-months

Overall Survival (OS)

Objective Response Rate (ORR)

Maximum Concentration (Cmax) at Study Day 1

Maximum Concentration (Cmax) at Study Day 15

Maximum Concentration (Cmax) at Study Day 16

Maximum Concentration (Cmax) at Study Day 30

Minimum Concentration (Cmin) at Study Day 1

Minimum Concentration (Cmin) at Study Day 15

Minimum Concentration (Cmin) at Study Day 16

Minimum Concentration (Cmin) at Study Day 30

Detailed description: Prostate cancer is the most frequently diagnosed cancer in men and the second leading cause of cancer-related death in men in the United States. Chemotherapy, either as a single agent or in combination, may lead to clinical response, pain control, and/or improved quality of life. Docetaxel is now the first-line standard therapy for AIPC. Mitoxantrone was approved in 1996 for use in combination with corticosteroids as initial chemotherapy for pain related to advanced Hormone Refractory Prostate Cancer (HRPC). Hormonal manipulations and docetaxel-based chemotherapy are often effective in metastatic prostate cancer; however, disease becomes refractory to these interventions in the majority of men. Although mitoxantrone continues to be a significant agent in the treatment of HRPC, there exists a need for more efficacious therapy in docetaxel-refractory- AIPC. Because of the potential contribution of Insulin Like Growth Factor Receptor (IGF-IR) and VEGFR-2 mediated pathways in prostate cancer pathogenesis, it is hypothesized that each of these biological agents in combination with mitoxantrone and prednisone will result in clinically meaningful activity in AIPC. Therefore, ImClone plans to conduct a randomized Phase 2 trial to assess the safety and efficacy of IMC-A12 or IMC-1121B (ramucirumab) in combination with mitoxantrone and prednisone in participants with AIPC.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

Criteria:

Inclusion Criteria:

- The participant has histologically-confirmed adenocarcinoma of the prostate

- The participant has radiographic evidence of metastatic prostate cancer (stage M1 or

D2)

- The participant has prostate cancer unresponsive or refractory to hormone therapy

(androgen-independent)

- The participant has had disease progression (clinical or radiographic) while

receiving docetaxel, or within 120 days of receiving docetaxel-based chemotherapy and in the opinion of the investigator is unlikely to derive significant benefit from additional docetaxel-based therapy, or was intolerant to therapy with this agent

- The participant must have evidence of progressive disease defined as at least one of

the following; 1. Progressive measurable disease: using conventional solid tumor criteria 2. Bone scan progression: at least two new lesions on bone scan 3. Increasing PSA: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2

- The participant has a PSA ≥ 2 ng/mL

- The participant has prior surgical or medical castration with a serum testosterone of

<50 ng/mL. If the method of castration is luteinizing hormone releasing level hormone (LHRH) agonists, the participant must be willing to continue the use of LHRH agonists during protocol treatment

- The participant has an Eastern Cooperative Oncology Group performance status (ECOG

PS) 0-2

- The participant has adequate hematologic function (absolute neutrophil count

[ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL)

- The participant has adequate hepatic function (bilirubin ≤ 1. 5 times the upper limit

of normal (ULN), Aspartate Transaminase (AST) and Alanine Transaminase (ALT) ≤ 3 times the ULN, or ≤ 5 times the ULN if liver metastases are present)

- The participant has adequate renal function (creatinine ≤ 1. 5 x ULN or calculated

creatinine clearance > 40 mL/min)

- The participant's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA). If

urine dipstick or routine analysis indicates ≥ 2+ proteinuria, then a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study

- The participant has adequate coagulation function (an international normalized ratio

[INR] ≤ 1. 5 and a Partial Thromboplastin Time [PTT] ≤ 5 seconds above the ULN [unless on oral anticoagulant therapy]). Participants receiving full-dose anticoagulation therapy are eligible provided they meet all other criteria, are on a stable dose of oral anticoagulant or low molecular weight heparin (and if on warfarin have a therapeutic INR between 2 and 3)

- The participant has a fasting serum glucose level of < 160 mg/dL, or below the ULN

Exclusion Criteria:

- The participant has received more than one prior cytotoxic chemotherapy regimen for

metastatic disease. (Participants who have had a treatment break followed by a second docetaxel-based regimen with subsequent disease progression are eligible.)

- The participant has received prior therapy with mitoxantrone for advanced prostate

cancer (prior adjuvant therapy with mitoxantrone is permitted)

- The participant has a history of symptomatic congestive heart failure or has a

pre-study echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) that is ≥ 10% below the LLN

- The participant has received radiotherapy ≤ 21 days prior to first dose of IMC-A12 or

Ramucirumab

- The participant is receiving corticosteroids (dexamethasone, prednisone, or others)

at a dose > 5 mg prednisone orally (PO) two times per day (BID) or equivalent. Participants receiving corticosteroids at higher doses may be eligible if their corticosteroid therapy is tapered to study levels (prednisone 5 mg PO BID) prior to first dose of study medication, without concomitant clinical deterioration

- The participant has known or suspected brain or leptomeningeal metastases

- The participant has uncontrolled or poorly controlled hypertension

- The participant has poorly controlled diabetes mellitus. Inclusion Criteria:

- The participant has histologically-confirmed adenocarcinoma of the prostate

- The participant has radiographic evidence of metastatic prostate cancer (stage M1 or

D2)

- The participant has prostate cancer unresponsive or refractory to hormone therapy

(androgen-independent)

- The participant has had disease progression (clinical or radiographic) while

receiving docetaxel, or within 120 days of receiving docetaxel-based chemotherapy and in the opinion of the investigator is unlikely to derive significant benefit from additional docetaxel-based therapy, or was intolerant to therapy with this agent

- The participant must have evidence of progressive disease defined as at least one of

the following; 1. Progressive measurable disease: using conventional solid tumor criteria 2. Bone scan progression: at least two new lesions on bone scan 3. Increasing PSA: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2

- The participant has a PSA ≥ 2 ng/mL

- The participant has prior surgical or medical castration with a serum testosterone of

<50 ng/mL. If the method of castration is luteinizing hormone releasing level hormone (LHRH) agonists, the participant must be willing to continue the use of LHRH agonists during protocol treatment

- The participant has an Eastern Cooperative Oncology Group performance status (ECOG

PS) 0-2

- The participant has adequate hematologic function (absolute neutrophil count

[ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL)

- The participant has adequate hepatic function (bilirubin ≤ 1. 5 times the upper limit

of normal (ULN), aspartate transaminase [AST] and alanine transaminase [ALT]≤ 3 times the ULN, or ≤ 5 times the ULN if liver metastases are present)

- The participant has adequate renal function (creatinine ≤ 1. 5 x ULN or calculated

creatinine clearance > 40 mL/min)

- The participant's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA). If

urine dipstick or routine analysis indicates ≥ 2+ proteinuria, then a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study

- The participant has adequate coagulation function (an international normalized ratio

[INR] ≤ 1. 5 and a partial thromboplastin time [PTT] ≤ 5 seconds above the ULN [unless on oral anticoagulant therapy]). Participants receiving full-dose anticoagulation therapy are eligible provided they meet all other criteria, are on a stable dose of oral anticoagulant or low molecular weight heparin (and if on warfarin have a therapeutic INR between 2 and 3)

- The participant has a fasting serum glucose level of < 160 mg/dL, or below the ULN

Exclusion Criteria:

- The participant has received more than one prior cytotoxic chemotherapy regimen for

metastatic disease. (Participants who have had a treatment break followed by a second docetaxel-based regimen with subsequent disease progression are eligible.)

- The participant has received prior therapy with mitoxantrone for advanced prostate

cancer (prior adjuvant therapy with mitoxantrone is permitted)

- The participant has a history of symptomatic congestive heart failure or has a

pre-study echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) that is ≥ 10% below the LLN

- The participant has received radiotherapy ≤ 21 days prior to first dose of IMC-A12 or

Ramucirumab

- The participant is receiving corticosteroids (dexamethasone, prednisone, or others)

at a dose > 5 mg prednisone orally (PO) two times per day (BID) or equivalent. Participants receiving corticosteroids at higher doses may be eligible if their corticosteroid therapy is tapered to study levels (prednisone 5 mg PO BID) prior to first dose of study medication, without concomitant clinical deterioration

- The participant has known or suspected brain or leptomeningeal metastases

- The participant has uncontrolled or poorly controlled hypertension

- The participant has poorly controlled diabetes mellitus. Participants with a history

of diabetes are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition

- The participant has a known human immunodeficiency virus infection or acquired

immunodeficiency syndrome-related illness with a history of diabetes are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition

- The participant has a known human immunodeficiency virus infection or acquired

immunodeficiency syndrome-related illness

Locations and Contacts

ImClone Investigational Site, La Jolla, California 92093, United States

ImClone Investigational Site, New Haven, Connecticut 06520, United States

ImClone Investigational Site, Boca Raton, Florida 33486, United States

ImClone Investigational Site, Port St. Lucie, Florida 34952, United States

ImClone Investigational Site, Atlanta, Georgia 30318, United States

ImClone Investigational Site, Chicago, Illinois 60611, United States

ImClone Investigational Site, Chlcago, Illinois 60637, United States

ImClone Investigational Site, Evanston, Illinois 60201, United States

ImClone Investigational Site, Maryville, Illinois 62062, United States

ImClone Investigational Site, Cedar Rapids, Iowa 52402, United States

ImClone Investigational Site, Metairie, Louisiana 70006, United States

ImClone Investigational Site, Ann Arbor, Michigan 48109, United States

ImClone Investigational Site, Rochester, Minnesota 55905, United States

ImClone Investigational Site, St Louis, Missouri 63110, United States

ImClone Investigational Site, Billings, Montana 59101, United States

ImClone Investigational Site, Roseland, New Jersey 07068, United States

ImClone Investigational Site, Buffalo, New York 14263, United States

ImClone Investigational Site, East Setauket, New York 11733, United States

ImClone Investigational Site, New York, New York 10032, United States

ImClone Investigational Site, New York, New York 10019, United States

ImClone Investigational Site, New York, New York 10021, United States

ImClone Investigational Site, New York, New York 10016, United States

ImClone Investigational Site, Durham, North Carolina 27710, United States

ImClone Investigational Site, Cleveland, Ohio 44195, United States

ImClone Investigational Site, Philadelphia, Pennsylvania 19111, United States

ImClone Investigational Site, Pittsburgh, Pennsylvania 15232, United States

ImClone Investigational Site, Greenville, South Carolina 29605, United States

ImClone Investigational Site, Knoxville, Tennessee 37920, United States

ImClone Investigational Site, Nashville, Tennessee 37203, United States

ImClone Investigational Site, Abilene, Texas 79606, United States

ImClone Investigational Site, Dallas, Texas 75246, United States

ImClone Investigational Site, Houston, Texas 77030-4009, United States

ImClone Investigational Site, Houston, Texas 77030, United States

ImClone Investigational Site, Seattle, Washington 98104, United States

ImClone Investigational Site, Seattle, Washington 98109, United States

ImClone Investigational Site, Madison, Wisconsin 53792, United States

Additional Information

Starting date: August 2008
Last updated: October 7, 2014

Page last updated: August 23, 2015

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