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Platinum Resistant Ovarian Cancer Evaluation of Doxil and EC145 Combination Therapy (PRECEDENT)
This study is currently recruiting participants.
Verified by Endocyte, April 2009
First Received: July 23, 2008   Last Updated: April 16, 2009   History of Changes
Sponsored by: Endocyte
Information provided by: Endocyte
ClinicalTrials.gov Identifier: NCT00722592
  Purpose

The objective of this study is to compare progression-free survival (PFS) in subjects with platinum-resistant ovarian cancer who receive combination therapy with EC145 and pegylated liposomal doxorubicin (PLD/Doxil®/Caelyx®)versus PLD alone.


Condition Intervention Phase
Ovarian Cancer
Drug: EC145
Drug: pegylated liposomal doxorubicin (PLD)
Drug: EC20
Phase II

MedlinePlus related topics: Cancer Ovarian Cancer
Drug Information available for: Doxorubicin Doxorubicin hydrochloride Myocet
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title: 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

Further study details as provided by Endocyte:

Primary Outcome Measures:
  • Progression-free survival based upon investigator assessment [ Time Frame: Assessed within 12 months following completion of accrual ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Compare overall survival between the two treatment arms [ Time Frame: Assessed at 18 months after initiation of PFS analysis ] [ Designated as safety issue: No ]
  • Evaluate the safety and tolerability of EC145 in combination with PLD [ Time Frame: event driven ] [ Designated as safety issue: Yes ]
  • Compare investigator assessed PFS based on RECIST in subjects with measurable disease at study entry [ Time Frame: Assessed within 12 months following completion of accrual ] [ Designated as safety issue: No ]
  • Compare objective response rate based on investigator assessment when analyzed using GCIG criteria and RECIST [ Time Frame: event-driven ] [ Designated as safety issue: No ]
  • Compare duration of response when analyzed using GCIG criteria and RECIST [ Time Frame: event-driven ] [ Designated as safety issue: No ]

Estimated Enrollment: 122
Study Start Date: September 2008
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A: Experimental
EC145 + Pegylated Liposomal Doxorubicin (PLD)
Drug: EC145
2.5 mg IV bolus on days 1,3,5 and 15,17,19 of a 4-week cycle
Drug: pegylated liposomal doxorubicin (PLD)
50 mg/m2 (with dose based on ideal body weight for subjects whose measured body weight is greater than their ideal body weight) intravenous infusion on day 1 of a 4 week cycle. Dose reductions permitted for toxicity.
Drug: EC20
During the screening period, subjects with measurable disease at baseline will receive a single intravenous injection of 0.1 mg EC20 labeled with 20-25 mCi technetium-99m followed by an imaging procedure.
Drug: EC20
During the follow-up period, subjects in Arm A with measurable disease at baseline will have the option of receiving a single intravenous injection of 0.1 mg EC20 labeled with 20-25 mCi technetium-99m followed by an imaging procedure.
B: Active Comparator
Pegylated Liposomal Doxorubicin (PLD)
Drug: pegylated liposomal doxorubicin (PLD)
50 mg/m2 (with dose based on ideal body weight for subjects whose measured body weight is greater than their ideal body weight) intravenous infusion on day 1 of a 4 week cycle. Dose reductions permitted for toxicity.
Drug: EC20
During the screening period, subjects with measurable disease at baseline will receive a single intravenous injection of 0.1 mg EC20 labeled with 20-25 mCi technetium-99m followed by an imaging procedure.

Detailed Description:

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.

All patients with measurable disease will also undergo imaging with the FR-targeting investigational diagnostic agent EC20 (FolateScan) 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 either one or both of the following:

    1. At least a single measurable lesion (by RECIST criteria) on a radiological evaluation that is conducted no more than 4 weeks prior to beginning study therapy (EC145 and/or PLD), or
    2. Screening CA-125 ≥ 2 x upper limit of normal (ULN)
  • 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 regimen
    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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00722592

  Show 53 Study Locations
Sponsors and Collaborators
Endocyte
Investigators
Study Director: Richard A Messmann, MD, MHS, MSc Endocyte
  More Information

Additional Information:
No publications provided

Responsible Party: Endocyte, Inc. ( Richard Messmann, MD / Vice-President, Medical Affairs )
Study ID Numbers: EC-FV-04
Study First Received: July 23, 2008
Last Updated: April 16, 2009
ClinicalTrials.gov Identifier: NCT00722592     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Endocyte:
cancer
ovarian
platinum-resistant
Phase II
EC145
EC20

Study placed in the following topic categories:
Genital Diseases, Female
Anti-Bacterial Agents
Ovarian Neoplasms
Gonadal Disorders
Genital Neoplasms, Female
Ovarian Cancer
Endocrine System Diseases
Urogenital Neoplasms
Endocrinopathy
Ovarian Diseases
Doxorubicin
Endocrine Gland Neoplasms

Additional relevant MeSH terms:
Ovarian Neoplasms
Antineoplastic Agents
Gonadal Disorders
Genital Neoplasms, Female
Endocrine System Diseases
Urogenital Neoplasms
Ovarian Diseases
Antibiotics, Antineoplastic
Pharmacologic Actions
Doxorubicin
Adnexal Diseases
Genital Diseases, Female
Neoplasms
Neoplasms by Site
Therapeutic Uses
Endocrine Gland Neoplasms

ClinicalTrials.gov processed this record on May 07, 2009