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Study for Women With Platinum Resistant Ovarian Cancer Evaluating EC145 in Combination With Doxil® (PROCEED)

This study has suspended participant recruitment.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01170650
First received: July 7, 2010
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to compare progression-free survival (PFS) (based upon investigator assessment using RECIST v1.1) in participants with platinum-resistant ovarian cancer who receive combination therapy with EC145 and pegylated liposomal doxorubicin (EC145+PLD) with that in participants who receive PLD and placebo.


Condition Intervention Phase
Ovarian Cancer
Drug: EC145
Drug: Pegylated Liposomal Doxorubicin (PLD/Doxil®/Caelyx®)
Drug: placebo
Drug: EC20
Phase 3

Study Type: 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
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Progression-free survival based on investigator assessment using RECIST v1.1. [ Time Frame: up to 26 months ] [ Designated as safety issue: No ]
    Progression is assessed at 6 week intervals through Week 24 and at 8 week intervals thereafter.


Secondary Outcome Measures:
  • Compare overall survival of participants between treatment arms. [ Time Frame: Approximately 20 months after last patient randomized ] [ Designated as safety issue: No ]
    OS analysis will occur when 384 deaths have occurred.

  • Incidence of Adverse Events, Serious Adverse Events, and Deaths. [ Time Frame: up to 26 months ] [ Designated as safety issue: Yes ]
    Adverse events (as a measure of safety and tolerability) will be assessed at each study visit.


Estimated Enrollment: 640
Study Start Date: April 2011
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
EC145 + Pegylated Liposomal Doxorubicin (PLD)
Drug: EC145
IV bolus on days 1,3,5 and 15,17,19 of a 4-week cycle
Drug: Pegylated Liposomal Doxorubicin (PLD/Doxil®/Caelyx®)
50 mg/m2 (calculated on the basis of ideal body weight) every 4 weeks. Dose reductions permitted for toxicity.
Other Names:
  • Doxil
  • Caelyx
Drug: EC20
During the screening period participants will receive a single intravenous administration of EC20 prior to SPECT imaging
Active Comparator: Arm B
placebo + Pegylated Liposomal Doxorubicin (PLD)
Drug: Pegylated Liposomal Doxorubicin (PLD/Doxil®/Caelyx®)
50 mg/m2 (calculated on the basis of ideal body weight) every 4 weeks. Dose reductions permitted for toxicity.
Other Names:
  • Doxil
  • Caelyx
Drug: placebo
IV bolus on days 1,3,5 and 15,17,19 of a 4-week cycle
Drug: EC20
During the screening period participants will receive a single intravenous administration of EC20 prior to SPECT imaging

Detailed Description:

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.

  Eligibility

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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01170650

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Binh Nguyen, MD Endocyte
  More Information

Additional Information:
No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01170650     History of Changes
Other Study ID Numbers: 8109-002, EC-FV-06
Study First Received: July 7, 2010
Last Updated: May 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
cancer
ovarian
platinum-resistant
Phase III
EC145
EC20

Additional relevant MeSH terms:
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 24, 2014