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A Randomized Phase II Trial Comparing EC145 and Pegylated Liposomal Doxorubicin (PLD/Doxil/Caelyx) in Combination, Versus PLD Alone, in Subjects With Platinum-Resistant Ovarian Cancer

Phase 2
18 Years
Not Enrolling
Ovarian Cancer

Thank you

Trial Information

A Randomized Phase II Trial Comparing EC145 and Pegylated Liposomal Doxorubicin (PLD/Doxil/Caelyx) in Combination, Versus PLD Alone, in Subjects With Platinum-Resistant Ovarian Cancer

This is a Phase II clinical trial to evaluate the efficacy and safety of the combination of
EC145 and pegylated liposomal doxorubicin (PLD; available in the United States as Doxil® and
outside the United States as Caelyx®) compared to PLD alone.

EC145 is a drug that is specifically designed to enter cancer cells via the folate vitamin
receptor (FR). Experimental evidence shows that this target receptor is expressed on
virtually all ovarian cancers. Early clinical evidence in a small number of Phase I subjects
and in a subset of subjects in an on-going single-arm Phase II study suggests that EC145 may
have antitumor effect in women with advanced ovarian cancer and that it is generally
well-tolerated. This evidence suggests that EC145 may be useful as chemotherapy against
advanced ovarian cancer.

Patients at centers with EC20 imaging capability will also undergo imaging with the
FR-targeting investigational diagnostic agent EC20 during the screening period to assess
uptake of this agent into tumors. This non-invasive procedure will provide additional
information on the utility of EC20 imaging to identify subjects with the FR molecular
"target" before treatment with EC145 therapy.

Inclusion Criteria:

To qualify for randomization and treatment the following criteria must be met:

- Subjects must sign an approved informed consent form

- Subjects must be ≥ 18 years of age

- Subjects must have pathology-confirmed epithelial ovarian, fallopian tube, or primary
peritoneal carcinoma

- Subjects must have platinum-resistant ovarian cancer, where platinum-resistant is
defined as disease that responded to primary platinum therapy and then progressed
within 6 months or disease that progressed during or within 6 months of completing
secondary platinum therapy

- Subjects must have at least a single (RECIST-defined) measurable lesion on a
radiological evaluation that is conducted no more than four weeks prior to beginning
study therapy (EC145 and/or PLD).

- Subjects must have had prior debulking surgery

- Subjects must have received prior platinum-based chemotherapy but must not have
received more than 2 prior systemic cytotoxic regimens. Subjects are allowed to
receive, but are not required to receive, one additional non-cytotoxic regimen for
the management of recurrent or persistent disease. Non-cytotoxic (biologic or
cytostatic) agents include, but are not limited to, monoclonal antibodies, cytokines,
and small-molecule inhibitors of signal transduction.

- Subjects must have an ECOG performance status of 0 to 2

- Subjects must have recovered (to baseline/stabilization) from prior cytotoxic
therapy-associated acute toxicities. Subjects who have recovered from non-cytotoxic
therapy-associated toxicity or who have "controlled" non-cytotoxic therapy toxicity
(e.g., vascular endothelial growth factor-related hypertension) can be entered into
the trial after a drug wash-out period of 4 half lives

- Subjects must have adequate organ function including:

1. Bone Marrow Reserve: Absolute neutrophil count(ANC)≥ 1.5x10^9/L prior to
treatment. Subjects on maintenance doses of G-CSF are eligible. Platelets ≥
100x10^9/L and hemoglobin ≥ 9 g/dL.

2. Hepatic: Total bilirubin level < 1.5 x ULN and alanine aminotransferase (ALT),
aspartate aminotransferase (AST), gamma glutamyl transferase(GGT), and alkaline
phosphatase levels < 2.5 x ULN.

3. Renal: Serum creatinine level ≤ 1.5 x ULN or creatinine clearance ≥ 50
mL/min/1.73m^2 for subjects with serum creatinine levels above 1.5 x ULN.

4. Cardiac: Left ventricular ejection fraction (LVEF) equal to or greater than the
institutional lower limit of normal. LVEF must be elevated within 90 days prior
to C1D1.

- Subjects of childbearing potential must:

1. Have a negative serum pregnancy test prior to initiation of the therapeutic

2. Practice an effective method of birth control (e.g., oral, transdermal or
injectable contraceptives, intrauterine device, double-barrier contraception,
such as diaphragm and spermicidal jelly) for the duration of their participation
in the trial through 3 months following the last dose of study drug.

Exclusion Criteria:

The presence of any of the following will exclude the subject from the study:

- Diagnosis of tumor of low-malignant potential

- Prior exposure to PLD or anthracycline therapy

- Prior exposure to FR-targeted therapy (EC145, EC0225, farletuzumab, etc)

- Prior therapy with mouse antibodies

- Prior therapy with vinorelbine (Navelbine®) or vinca-containing compounds

- Prior abdominal or pelvic radiation therapy, radiation therapy to > 10% of the bone
marrow, or prior radiation therapy within the past 3 years to the breast/sternum,
dermal lesions, head or neck

- Recent (i.e., ≤ 6 weeks) history of abdominal surgery or peritonitis

- Serious comorbidities (as determined by the investigator) such as, but not limited
to, active congestive heart failure or recent myocardial infarction. Subjects who
require antifolate therapy for the management of comorbid conditions (e.g.,
rheumatoid arthritis) will be excluded from the trial.

- Pregnancy

- Concurrent malignancy or history of other cancer (except noninvasive skin cancer)
within the last 5 years

- Symptomatic central nervous system metastasis

- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy
that is considered to be investigational (i.e., used for non-approved indications(s)
and in the context of a research investigation). Use of low dose corticosteroid
therapy (for nausea prophylaxis, etc) is acceptable; however, concomitant tamoxifen
therapy is not. Supportive care measures are allowed.

Type of Study:


Study Design:

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

Outcome Measure:

Progression-free survival based on investigator assessment using RECIST and clinical findings

Outcome Time Frame:

Assessed within 12 months following completion of accrual

Safety Issue:


Principal Investigator

Richard A Messmann, MD, MHS, MSc

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

September 2008

Completion Date:

December 2012

Related Keywords:

  • Ovarian Cancer
  • cancer
  • ovarian
  • platinum-resistant
  • Phase II
  • EC145
  • EC20
  • Ovarian Neoplasms



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Beth Israel Deaconess Medical Center Boston, Massachusetts  02215
MD Anderson Cancer Center Orlando Orlando, Florida  32806
Dana-Farber Cancer Institute Boston, Massachusetts  02115
Carilion Gynecologic Oncology Associates Roanoke, Virginia  24014
Moores UCSD Cancer Center La Jolla, California  92093-0658
Massachusetts General Hospital Boston, Massachusetts  02114-2617
Missouri Cancer Associates Columbia, Missouri  65201
Arizona Clinical Research Center Tucson, Arizona  85712
Medical College of Georgia Augusta, Georgia  30912
Cancer Care Northwest Spokane, Washington  99202
Broward Oncology Associates Ft. Lauderdale, Florida  33308
Dartmouth Hitchcock Medical Center Lebanon, New Hampshire  03756
Metro Minnesota CCOP St. Louis Park, Minnesota  55416
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Gabrail Cancer Center Canton, Ohio  44718
Pasco Pinellas Cancer Center New Port Richey, Florida  34652
St. Vincent Gynecologic Oncology Indianapolis, Indiana  46260
Minnesota Oncology Hematology, P.A. Minneapolis, Minnesota  55407
South Austin Cancer Center Austin, Texas  78745
Yale University School Of Medicine New Haven, Connecticut  06520
Schwartz Gynecologic Oncology Brightwaters, New York  11718
Chattanooga's Program in Women's Oncology Chattanooga, Tennessee  37403
Northwest Cancer Specialists, P.C. Vancouver, Washington  
Kapiolani Medical Center for Women & Children Honolulu, Hawaii  96826
Northern Arizona Hematology and Oncology Associates Flagstaff, Arizona  86001
Northern Arizona Hematology & Oncology Associates Sedona, Arizona  86336
Puget Sound Cancer Centers Edmonds, Washington  98026
Brody School of Medicine Greenville, North Carolina  27858
Horizon Oncology Center Lafayette, Indiana  47905
Karmanos Cancer Center Detroit, Michigan  48201
Texas Oncology Cancer Care and Research Center Waco, Texas  76712
New York Downtown Hospital New York, New York  10038
Greater Cincinnati OB/GYN, Inc. Cincinnati, Ohio  45267
Swedish Medical Center Cancer Institute Seattle, Washington  98104
Women's Cancer Research Foundation Newport Beach, California  92663
Center for Blood and Cancer Disorders Bethesda, Maryland  20817
Texas Oncology-Central Austin Cancer Center Austin, Texas  78731
Cancer Treatment Centers of America (CTCA-Midwestern) Zion, Illinois  60099
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Cancer Center of Northwest, P. A. -North Spokane, Washington  99218
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