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A Randomized Double-Blind Phase 3 Trial Comparing EC145 and Pegylated Liposomal Doxorubicin (PLD/Doxil®/Caelyx®) in Combination Versus PLD in Participants With Platinum-Resistant Ovarian Cancer


Phase 3
18 Years
N/A
Open (Enrolling)
Female
Ovarian Cancer

Thank you

Trial Information

A Randomized Double-Blind Phase 3 Trial Comparing EC145 and Pegylated Liposomal Doxorubicin (PLD/Doxil®/Caelyx®) in Combination Versus PLD in Participants With Platinum-Resistant Ovarian Cancer


This is a Phase 3 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 and placebo. Enrollment of 640
patients including approximately 500 that are folate receptor positive is planned.

EC145 is a drug that is specifically designed to enter cancer cells via the folate vitamin
receptor (FR) that is not generally found on normal cells. Experimental evidence shows that
this target receptor is expressed on virtually all ovarian cancers. Early clinical evidence
in a small number of Phase I participants, in a subset of participants in a completed
single-arm Phase II study, and interim data from an ongoing randomized Phase 2 study
(PRECEDENT) suggests that EC145 may have antitumor effect in women with platinum-resistant
ovarian cancer and that EC145 alone and in combination with PLD is generally well-tolerated.
This evidence suggests that EC145 may be useful as chemotherapy against platinum-resistant
ovarian cancer.

All participants will undergo imaging with the FR-targeting investigational diagnostic agent
EC20 during the screening period to assess binding of the imaging agent EC20 to tumors. This
non-invasive procedure will provide additional information on the utility of using EC20
imaging to identify subjects with the FR molecular "target" prior to treatment with EC145
therapy.


Inclusion Criteria:



- Participants must sign an approved informed consent form (ICF).

- Participants must be ≥ 18 years of age.

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

- Participants must have primary or secondary platinum-resistant ovarian cancer.

- Participants must have at least a single (RECIST v1.1-defined) measurable lesion.

- For the purpose of obtaining a RECIST v1.1 baseline scan, participants must have a
radiological evaluation conducted no more than 28 days prior to beginning study
therapy (PLD). NOTE: For participants with a history of CNS metastasis, baseline
radiological imaging must include an evaluation of the head.

- Participants must have had prior debulking surgery.

- Participants must have received prior platinum-based chemotherapy for management of
primary disease but must not have received more than 2 prior systemic cytotoxic
regimens.

- Participants are allowed to have received, but are not required to have received, one
additional non-cytotoxic antitumor agent (eg, biologic or cytostatic) for the
management of ovarian cancer.

- Participants must have an Eastern Cooperative Oncology Group (ECOG) performance
status of 0 to 1.

- Participants must have recovered (to baseline/stabilization) from prior cytotoxic
therapy-associated acute toxicities.

- Participants must have adequate organ function including:

1. Bone Marrow Reserve:

1. Absolute neutrophil count (ANC) ≥ 1.5x10^9/L prior to treatment.
Participants on maintenance doses of granulocyte colony stimulating factor
(G-CSF) are eligible.

2. Platelets ≥ 100x10^9/L

3. Hemoglobin ≥ 9 g/dL

4. Use of supportive care measures (eg, use of white blood cell [WBC] growth
factors, antiemetics, epoetin) should follow the ASCO guidelines as listed
at www.asco.org. Participants should receive full supportive care,
including transfusion of blood as mandated by clinical need; however,
transfusions administered for the sole purpose of meeting the study
inclusion criteria between the time informed consent is signed and first
dose of EC145/placebo/PLD is administered are not allowed.

2. Hepatic: Total bilirubin level < 1.5 x ULN and ALT, AST, GGT, and alkaline
phosphatase levels < 2.5 x ULN.

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

4. Cardiac: Left ventricular ejection fraction (LVEF) equal to or greater than the
institutional lower limit of normal.

Exclusion Criteria:

- Patients refractory to primary platinum therapy where "refactory" is defined as
disease progression within 6 months of first dose of initial platinum-based therapy.

- Diagnosis of "tumor of low-malignant potential".

- Prior exposure to PLD or anthracycline therapy.

- Prior exposure to FR-targeted therapy (eg, EC145, EC0225, EC0489, farletuzumab).

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

- Prior abdominal or pelvic radiation therapy or radiation therapy to > 10% of the bone
marrow at any time in the past 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. Patients who
require antifolate therapy for the management of comorbid conditions (e.g.,
rheumatoid arthritis) will be excluded from the trial.

- Pregnant or nursing.

- Concurrent malignancy requiring therapy (excluding non-invasive carcinoma or
carcinoma in situ).

- Symptomatic central nervous system (CNS) 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 (e.g., for nausea prophylaxis) is acceptable; however, concomitant tamoxifen
therapy is not. Supportive care measures are allowed.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Progression-free survival based on investigator assessment using RECIST v1.1.

Outcome Description:

Progression is assessed at 6 week intervals through Week 24 and at 8 week intervals thereafter.

Outcome Time Frame:

up to 26 months

Safety Issue:

No

Principal Investigator

Binh Nguyen, MD

Investigator Role:

Study Director

Investigator Affiliation:

Endocyte

Authority:

United States: Food and Drug Administration

Study ID:

EC-FV-06

NCT ID:

NCT01170650

Start Date:

April 2011

Completion Date:

May 2015

Related Keywords:

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

Name

Location

Mayo ClinicRochester, Minnesota  55905
Washington University School of MedicineSaint Louis, Missouri  63110
Abington Memorial HospitalAbington, Pennsylvania  19001
Sinai Hospital of BaltimoreBaltimore, Maryland  21225
Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
Morristown Memorial HospitalMorristown, New Jersey  07962-1956
Northwestern Memorial HospitalChicago, Illinois  60611
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Texas Oncology, P.A.Dallas, Texas  75246
Peninsula Regional Medical CenterSalisbury, Maryland  21801
Ochsner Clinic FoundationNew Orleans, Louisiana  70121
Toledo HospitalToledo, Ohio  43606
Mayo ClinicJacksonville, Florida  32224
Cancer Centers of the CarolinasGreenville, South Carolina  29605
Moores UCSD Cancer CenterLa Jolla, California  92093-0658
Bay Regional Medical CenterBay City, Michigan  48708
Massachusetts General HospitalBoston, Massachusetts  02114-2617
Missouri Cancer AssociatesColumbia, Missouri  65201
Miami Valley HospitalDayton, Ohio  45409
Southeastern Gynecologic OncologyDecatur, Georgia  30033
Medical College of GeorgiaAugusta, Georgia  30912
University of WashingtonSeattle, Washington  98195
University of California, San FranciscoSan Francisco, California  94143
Duke University Medical CenterDurham, North Carolina  27710
Kaiser Permanente Medical CenterVallejo, California  94589
California Pacific Medical CenterSan Francisco, California  94115
Oncology Associates of San DiegoSan Diego, California  92123
Blumenthal Cancer CenterCharlotte, North Carolina  28203
Texas OncologyDallas, Texas  
St. Vincent Gynecologic OncologyIndianapolis, Indiana  46260
Chattanooga GYN OncologyChattanooga, Tennessee  37403
Decatur Memorial HospitalDecatur, Illinois  62526
Yale University School Of MedicineNew Haven, Connecticut  06520
Providence Saint Joseph Medical CenterBurbank, California  91505-4866
Memorial Health University Medical CenterSavannah, Georgia  31404
Northern Indiana Cancer Research ConsortiumSouth Bend, Indiana  
Nevada Cancer InstituteLas Vegas, Nevada  89135
Chattanooga's Program in Women's OncologyChattanooga, Tennessee  37403
University of Maryland Medical CenterBaltimore, Maryland  21201-1595
Mayo Clinic ArizonaScottsdale, Arizona  85259
Northside HospitalAtlanta, Georgia  30342
Multicare Health SystemTacoma, Washington  98415
Cancer and Blood Disease CenterLecanto, Florida  34461
Horizon Oncology CenterLafayette, Indiana  47905
Karmanos Cancer CenterDetroit, Michigan  48201
Schwartz Gynecologic Oncology, PLLCBabylon, New York  11702
Mount Clemens Regional Medical CenterMount Clemens, Michigan  48043
Gynecologic Oncology Associates, IncHollywood, Florida  33020
Willamette Valley Cancer Institute and Research CenterSpringfield, Oregon  97477
Columbia Basin Hematology and OncologyKennewick, Washington  99336
Center for Blood and Cancer DisordersBethesda, Maryland  20817
North American Research InstituteWest Covina, California  91790
Altus ResearchLake Worth, Florida  33461
Meritus Center For Clinical ResearchHagerstown, Maryland  21740
Scripps Clinical Research ServicesLa Jolla, California  92037
University of Arizona - Arizona Cancer CenterTuscon, Arizona  85724
Marin Caner Care, Inc.Greenbrae, California  94904
PMK Medical Group, Inc., dba Ventura County Hematology Oncology SpecialistsOxnard, California  93030
Stanford University Medical Center - Cancer CenterStandford, California  94305
Kaiser Permanente Vallejo Medical CenterVallejo, California  94589
St. Vincent's Medcial CenterBridgeport, Connecticut  06606
Palm Beach Cancer Institute - Palm Beach Cancer InstituteWest Palm Beach, Florida  33401
Sudarshan K. Sharma, LTDHinsdale, Illinois  60521
St. Francis Medical Group Gynecologic Oncology of IndianaIndianapolis, Indiana  46237
University of Louisville James Graham Brown Cancer CenterLouisville, Kentucky  40202
Singh & Arora Onc/Hem, PCFlint, Michigan  48532
MSU Breslin Cancer CenterLansing, Michigan  48910
Lapeer Regional Medical CenterLapeer, Michigan  48446
Providence Hospital and Medical CenterSouthfield, Michigan  48075
Bozeman Deaconess Hospital Cancer CenterBozeman, Montana  59715
Holy Name Medical CenterTeaneck, New Jersey  07666
Southwest Gynecologic Oncology AssociatesAlbuquerque, New Mexico  87106
Greater Cincinnati OB/GYN, IncCincinnati, Ohio  45267
Medical University of South Carolina, Dept. OB/GYNCharleston, South Carolina  29425
Texas Oncology- Central Austin Cancer CenterAustin, Texas  78731
Mary Crowley Medical City ClinicDallas, Texas  75230
Texas Oncology-Dallas, PA PresbyterianDallas, Texas  75231