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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


Phase 2
18 Years
N/A
Not Enrolling
Male
Prostate Cancer

Thank you

Trial Information

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


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 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 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 patients with AIPC.


Inclusion Criteria:



- The patient has histologically-confirmed adenocarcinoma of the prostate

- The patient has radiographic evidence of metastatic prostate cancer (stage M1 or D2)

- The patient has prostate cancer unresponsive or refractory to hormone therapy
(androgen-independent)

- 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

- The patient 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 patient has a PSA ≥ 2 ng/mL

- 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

- The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS)
0-2

- The patient has adequate hematologic function (absolute neutrophil count
[ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL)

- 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)

- The patient has adequate renal function (creatinine ≤ 1.5 x ULN or calculated
creatinine clearance > 40 mL/min)

- 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

- 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)

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

Exclusion Criteria:

- 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.)

- The patient has received prior therapy with mitoxantrone for advanced prostate cancer
(prior adjuvant therapy with mitoxantrone is permitted)

- 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

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

- 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

- The patient has known or suspected brain or leptomeningeal metastases

- The patient has uncontrolled or poorly controlled hypertension

- 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

- The patient has a known human immunodeficiency virus infection or acquired
immunodeficiency syndrome-related illness

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Progression-free survival (PFS)

Outcome Time Frame:

37 months

Safety Issue:

No

Principal Investigator

E-mail: ClinicalTrials@ ImClone.com

Investigator Role:

Study Director

Investigator Affiliation:

ImClone LLC

Authority:

United States: Food and Drug Administration

Study ID:

13924

NCT ID:

NCT00683475

Start Date:

August 2008

Completion Date:

September 2011

Related Keywords:

  • Prostate Cancer
  • Prostate Cancer
  • Prostatic Neoplasms

Name

Location

ImClone Investigational SiteGreenwich, Connecticut  06830
ImClone Investigational SiteNew York, New York  10021
ImClone Investigational SiteSt. Charles, Missouri  63301
ImClone Investigational SiteBakersfield, California  93309
ImClone Investigational SiteJacksonville, Florida  32207
ImClone Investigational SiteAtlanta, Georgia  30318
ImClone Investigational SiteDecatur, Illinois  62526
ImClone Investigational SiteNew Orleans, Louisiana  70121
ImClone Investigational SiteYpsilanti, Michigan  48198
ImClone Investigational SiteMinneapolis, Minnesota  55416
ImClone Investigational SiteGreat Falls, Montana  59405
ImClone Investigational SiteVoorhees, New Jersey  08043
ImClone Investigational SiteCleveland, Ohio  44134
ImClone Investigational SiteGreenville, South Carolina  29605
ImClone Investigational SiteMemphis, Tennessee  38104
ImClone Investigational SiteDallas, Texas  75230
ImClone Investigational SiteGreen Bay, Wisconsin  54307
ImClone Investigational SiteWinston-Salem, North Carolina  27103
ImClone Investigational SitePhiladelphia, Pennsylvania  19107
ImClone Investigational SiteSeattle, Washington  98104
ImClone Investigational SiteCedar Rapids, Iowa  52402