The purpose of this study is to determine whether IMC-A12 or IMC-1121B with Mitoxantrone and
Prednisone is effective in the treatment of metastatic androgen- independent prostate
cancer.
Inclusion Criteria:
1. The patient has histologically-confirmed adenocarcinoma of the prostate.
2. The patient has radiographic evidence of metastatic prostate cancer (stage M1 or D2).
3. The patient has prostate cancer unresponsive or refractory to hormone therapy
(androgen-independent).
4. The patient 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.
5. The patient must have evidence of progressive disease defined as at least one of the
following;a. Progressive measurable disease: using conventional solid tumor criteria
b. Bone scan progression: at least two new lesions on bone scan c. 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.
6. The patient has a PSA ≥ 2 ng/mL.
7. The patient 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 patient must be willing to continue the use of LHRH agonists
during protocol treatment.
8. All clinically significant toxic effects (excluding alopecia) of prior
surgery,radiotherapy, or hormonal therapy have resolved to ≤ Grade 1 based on the
NCI-CTCAE v 3. 0, with the exception of peripheral neuropathy, which must have
resolved to Grade ≤ 2.
9. The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS)
0-2.
10. The patient has adequate hematologic function (absolute neutrophil count
[ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL).
11. The patient 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).
12. The patient has adequate renal function (creatinine ≤ 1. 5 x ULN or calculated
creatinine clearance > 40 mL/min).
13. The patient'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.
14. The patient 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]). Patients 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).
15. The patient has a fasting serum glucose level of < 160 mg/dL, or below the ULN.
16. The patient has a life expectancy > 3 months.
17. The patient is male and at least 18 years of age.
18. The patient agrees to use contraceptives while on study if sexually active.
19. The patient has provided signed informed consent.
Exclusion Criteria:
1. The patient has any active malignancy (other than adequately treated nonmelanomatous
skin cancer or other noninvasive or in situ neoplasms) and there has been no evidence
of disease recurrence during the prior 3 years.
2. The patient has received more than one prior cytotoxic chemotherapy regimen for
metastatic disease. (Patients who have had a treatment break followed by a second
docetaxel-based regimen with subsequent disease progression are eligible.)
3. The patient has received prior therapy with mitoxantrone for advanced prostate cancer
(prior adjuvant therapy with mitoxantrone is permitted).
4. The patient 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.
5. The patient has a history of prior treatment with other agents that directly inhibit
IGF, IGFRs, VEGF, or VEGFRs.
6. The patient has known allergy to any of the treatment components.
7. The patient has received radiotherapy ≤ 21 days prior to first dose of IMC-A12 or
IMC-1121B.
8. The patient is receiving corticosteroids (dexamethasone, prednisone, or others) at a
dose > 5 mg prednisone orally (PO) two times per day (BID) or equivalent. Patients
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.
9. The patient has received prior strontium-89, rhenium-186, rhenium-188, or
samarium-153 radionucleotide therapy. Patients who have received standard dose
radiation to the pelvis for prostate cancer and/or additional external beam
radiotherapy to metastatic sites are eligible.
10. The patient has an ongoing or active infection, symptomatic congestive heart failure,
unstable angina pectoris, serious cardiac arrhythmia (well controlled atrial
fibrillation is permitted), psychiatric illness/social situations, active bleeding or
pathological condition that carries a high risk of bleeding (eg, tumor involving
major vessels, tumor invading to rectal lumen, or known varices), or any other
serious uncontrolled medical disorders in the opinion of the investigator.
11. The patient has known or suspected brain or leptomeningeal metastases.
12. The patient has uncontrolled or poorly controlled hypertension.
13. The patient has poorly controlled diabetes mellitus. Patients 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.
14. The patient has a known human immunodeficiency virus infection or acquired
immunodeficiency syndrome-related illness.
Moores UCSD Cancer Center, La Jolla, California 92093, United States; Recruiting
Arlene Araneta, Phone: 858-822-5374, Email: AAraneta@ucsd.edu
Frederick E Millard, MD, Principal Investigator
Yale University School of Medicine, New Haven, Connecticut 06520, United States; Recruiting
Elin Rowen, Phone: 203-737-2445
William Kelly, DO, Principal Investigator
Hematology Oncology Associates of the Treasure Coast, Port St. Lucie, Florida 34952, United States; Recruiting
Christine Gerdes, BSN,RN,OCN, Phone: 772-408-5159, Email: cgerdes@hemoncfl.com
Michael Wertheim, MD, Principal Investigator
Boca Raton Community Hospital Inc., Boca Raton, Florida 33486, United States; Recruiting
Bonnie Pesacov, Phone: 561-416-8896, Ext: 247, Email: bpesacov@brch.com
Alan J Koletsky, MD, Principal Investigator
Peachtree Hematology-Oncology Consultants, PC., Atlanta, Georgia 30309, United States; Recruiting
Ann Johnston, Phone: 678-298-3241, Email: AJohnston@phoc.com
Vasily Assikis, MD, Principal Investigator
Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, United States; Recruiting
Brenda Martone, Phone: 312-695-1366, Email: b-martone@northwestern.edu
Gary MacVicar, MD, Principal Investigator
Warren Billhartz Cancer Center, Maryville, Illinois 62062, United States; Recruiting
Wendy McIntyre, Phone: 618-288-9044, Email: McIntyreW@andersonhospital.org
John L Visconti, DO, Principal Investigator
University of Chlcago, Chlcago, Illinois 60637, United States; Recruiting
Walter Stadler., MD, Principal Investigator
North Shore University Health System, Evanston, Illinois 60201, United States; Recruiting
Daniel Shevrin, MD, Principal Investigator
lowa Blood & Cancer Care, P.L.C., Cedar Rapids, Iowa 52402, United States; Recruiting
Carlene Etscheidt, Phone: 319-369-7091, Email: cetscheidt@ibacc.org
David W Zenk, MD, Principal Investigator
Jayne Gurtler, Metairie, Louisiana 70006, United States; Recruiting
Jeannette Vicknair, Phone: 504-885-0577, Email: jvicknair@metairieoncologists.org
Jayne Gurtler, MD, Principal Investigator
University of Michigan Health System, Ann Arbor, Michigan 48109, United States; Recruiting
Joanna Ramos, Phone: 734-936-5308, Email: jramos@umich.edu
Muha Hussain, MD, Principal Investigator
Mayo Clinic, Rochester,, Minnesota 55905, United States; Recruiting
Washington University School of Medicine, St Louis, Missouri 63110, United States; Recruiting
Joel Picus, MD, Principal Investigator
Billings Clinic, Billings, Montana 59101, United States; Recruiting
James M Burke, MD, Principal Investigator
North Shore Hematology/Oncology Assoc., East Setauket, New York 11733, United States; Recruiting
Dorota ZaBorek, Phone: 631-751-3000, Ext: 170, Email: dzaborek@nshoa.com
Joanne Messina, Phone: 631-751-3000, Ext: 143, Email: jmessina@nshoa.com
Jeffrey Vacirca, MD, Principal Investigator
Roswell Park Cancer Institute, Buffalo, New York 14263, United States; Recruiting
Anita Sandecki, Phone: 716-845-8730, Email: Anita.Sandecki@roswellpark.org
Donald Trump, MD, FACP, Principal Investigator
Memorial Sloan-Kettering Cancer Center, New York, New York 10021, United States; Recruiting
Julia Shelkey, Phone: 646-227-2170, Email: shelkey@mskcc.org
Dana Rathkopf, MD, Principal Investigator
Columbia University Medical Company, New York, New York 10032, United States; Recruiting
Daniel P Petrylak, MD, Principal Investigator
NYU Clinical Cancer Center, New York, New York 10016, United States; Recruiting
Anna Ferrari, MD, Principal Investigator
St. Luke's Roosevelt Hospital Center, New York, New York 10019, United States; Recruiting
Seth Cohen, MD, Principal Investigator
Duke University Medical Center, Durham, North Carolina 27705, United States; Recruiting
Henry Bell, Phone: 919-668-8375, Email: Henry.Bell@duke.edu
Andrew J Armstrong, MD, Principal Investigator
Cleveland Clinic, Cleveland, Ohio 44195, United States; Recruiting
Allison Tyler, Phone: 216-445-0861, Email: TYLERA2@ccf.org
Robert Dreicer, MD, Principal Investigator
UPMC Cancer Pavilion, Pittsburgh, Pennsylvania 15232, United States; Recruiting
Gurkamal Chatta, MD, Principal Investigator
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, United States; Recruiting
Elizabeth Plimack, MD, Principal Investigator
University of Tennessee Medical Center, Knoxville, Tennessee 37920, United States; Recruiting
Randi Ray, Phone: 865-305-9773, Email: rrray@utmck.edu
Wahid T Hanna, MD, Principal Investigator
Sarah Cannon Cancer Center, Nashville, Tennessee 37203, United States; Recruiting
Ann Clay, Phone: 615-329-7233, Email: Ann.Clay@scresearch.net
John Hainsworth, MD, Principal Investigator
Mary Crowley Medical Research Center dba Mary Crowley Cancer Research Centers, Dallas, Texas 75246, United States; Recruiting
Alyssa Roth, Phone: 214-370-1865, Email: aroth@marycrowley.org
John J Nemunaitis, MD, Principal Investigator
Texas Oncology, PA Texas Cancer Center, Abilene, Texas 79606, United States; Recruiting
Anton M Melnyk, MD, Principal Investigator
The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Paul Matthew, MD, Principal Investigator
The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030-4009, United States; Recruiting
Paul Mathew, MD, Principal Investigator
The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Paul G Corn, MD, Ph.D, Principal Investigator
Swedish Cancer Institute, Seattle, Washington 98104, United States; Recruiting
Heather Reid, Phone: 206-386-2445, Email: heather.reid@swedish.org
Howard West, MD, Principal Investigator
Seattle Cancer Care Alliance, Seattle, Washington 98109, United States; Recruiting
Deborah Chielens, Phone: 206-288-1189, Email: DChielens@u-washington.edu
Celestia Higano, MD, Principal Investigator
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, Wisconsin 53792, United States; Recruiting
Dottie Horvath, Phone: 608-263-7107, Email: dlh@medicine.wisc.edu
Glenn Liu, MD, Principal Investigator
