A Study of Liposomal Doxorubicin With or Without Olaratumab (IMC-3G3) in Platinum-Refractory or Resistant Advanced Ovarian Cancer

NCT00913835 | Completed Phase 2 Results DMC

• 4 other identifiers: 138992009-009035-30CP15-0802I5B-IE-JGDA
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to determine if participants with platinum-refractory or platinum-resistant advanced ovarian cancer have a better outcome when treated with Olaratumab (IMC-3G3) in combination with Liposomal Doxorubicin than when treated with Liposomal Doxorubicin alone.

Conditions

Ovarian Neoplasms

Keywords

Liposomal Doxorubicin; IMC-3G3; 3G3; Platinum resistant; Platinum refractory; Ovary; Neoplasm; PDGFr

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS is defined as the time from the day of randomization to the first evidence of progression as defined by Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) criteria or death from any cause. Progressive Disease (PD) is a 20% increase over the smallest sum of target lesions or new lesions. Participants who died without a reported prior disease progression were considered to have progressed on the day of their death. Participants who did not progress and were subsequently lost to follow-up had their data censored at the day of last tumor assessment.

  Randomization to Progressive Disease (PD) or Date of Death (Up to 35 Months)

Secondary Outcomes (12)

• Overall Survival (OS)

  First Day of Therapy to Date of Death (Up to 35 Months)

• Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]

  Randomization to PD (Up to 35 Months)

• Median Duration of Response

  Date of Initial CR or PR to PD (Up to 35 Months)

• Number of Participants With Adverse Events (AEs) and Who Died

  Baseline Up to End of Treatment and 30-day Post-dose Follow-up (Up to 35 Months)

• Percentage of Participants With Anti-Olaratumab Antibodies

  Baseline Up to 30-Day Postdose Follow-Up (Up To 35 Months)

Study Arms (2)

Olaratumab and Liposomal Doxorubicin

EXPERIMENTAL

Olaratumab and Liposomal Doxorubicin

Biological: Olaratumab; Drug: liposomal doxorubicin

Liposomal Doxorubicin: Optional Olaratumab Monotherapy

ACTIVE COMPARATOR

Liposomal Doxorubicin Monotherapy until disease progression. Upon disease progression the participant had the option to receive Olaratumab monotherapy.

Biological: Olaratumab; Drug: liposomal doxorubicin

Interventions

Olaratumab BIOLOGICAL

20 milligrams per kilogram (mg/kg) administered by intervenous (IV) infusion every 2 weeks (14 days). Treatment will continue until there is evidence of progressive disease (PD) or development of unacceptable toxicity

Also known as: LY3012207, IMC-3G3

Liposomal Doxorubicin: Optional Olaratumab Monotherapy; Olaratumab and Liposomal Doxorubicin

liposomal doxorubicin DRUG

40 milligrams per square meter (mg/m²) administered according to the manufacture's instructions every 4 weeks (28 days). Treatment will continue until there is evidence of PD or development of unacceptable toxicity

Liposomal Doxorubicin: Optional Olaratumab Monotherapy; Olaratumab and Liposomal Doxorubicin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant has histologically or cytologically confirmed epithelial ovarian cancer, primary peritoneal carcinoma, fallopian tube cancer, or ovarian clear cell carcinoma
• The participant must have at least one of the following: a platinum-free interval of ≤12 months after the final dose of primary or subsequent platinum-based therapy (platinum-resistant), progression during primary or subsequent platinum-based therapy (platinum-refractory), or persistent radiographic disease after primary or subsequent platinum-based therapy (platinum-refractory)
• The participant has a pre-study echocardiogram or multigated acquisition (MUGA) scan with an actual left ventricular ejection fraction (LVEF) ≥50%, within 21 days prior to randomization
• The participant has at least one unidimensionally measurable target lesion \[≥20 millimeters (mm) with conventional techniques, or ≥10 mm by spiral computed tomography (CT) or magnetic resonance imaging (MRI)\], as defined by Response Evaluation Criteria in Solid Tumors, Version 1.0 (RECIST v1.0) guidelines. Tumors within a previously irradiated field will be designated as "nontarget" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
• The participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤1 at study entry
• The participant has the ability to understand and the willingness to sign a written informed consent
• The participant has adequate hematological functions \[absolute neutrophil count (ANC) ≥1200 cells/microliter (cells/μL), hemoglobin ≥9 grams/deciliter (g/dL), and platelets ≥100,000 cells/μL\]
• The participant has adequate hepatic function as defined by total bilirubin ≤1.5 × the upper limit of normal (ULN), and aspartate transaminase (AST) and alanine transaminase (ALT) ≤3 × the ULN (or ≤5 × the ULN in the presence of known liver metastases)
• The participant has adequate renal function as defined by serum creatinine ≤1.5 × the institutional ULN. If creatinine is above the ULN, the participant's creatinine clearance is ≥60 milliliters/minute (mL/min)
• The participant has urinary protein ≤1+ on dipstick or routine urinalysis; if urine dipstick or routine analysis is ≥2+, a 24-hour urine for protein must demonstrate \<1000 milligrams (mg) of protein to allow participation
• The participant must have adequate coagulation function as defined by International Normalized Ratio (INR) ≤1.5 and a partial thromboplastin time (PTT) ≤5seconds above ULN. Participants on anticoagulation must be on a stable dose of anticoagulant with a therapeutic INR and no active bleeding within 14 days prior to randomization, or on low molecular weight heparin AND have no pathological condition carrying a high risk of bleeding. Mild elevations of PTT of up to 1.5 × the ULN are acceptable, provided that, in the opinion of the investigator, they are related to ongoing use of coumarins \[for example (e.g.), warfarin\]
• The participant has a pre-study echocardiogram or MUGA scan with an actual LVEF ≥50%, within 21 days prior to randomization
• Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to randomization and for the duration of study participation

You may not qualify if:

• The participant has brain metastases or leptomeningeal disease
• The participant received more than one biologic and/or more than one hormonal therapy, administered either concomitantly with platinum-based therapy or separately
• The participant has a history of treatment with other agents targeting platelet derived growth factor (PDGF) or PDGF receptor (PDGFR)
• The participant has an increased level of cancer antigen-125 (CA-125) in the absence of concomitant clinical or radiographic progression
• The participant has received radiotherapy, chemotherapy, or biologic therapy directed at the malignant tumor within 3 weeks prior to randomization, or hormonal therapy directed at the malignant tumor within 1 week prior to randomization. Continuation of hormone replacement therapy is permitted
• The participant has a suspected impending bowel obstruction (including partial obstruction), based on clinical or radiographic data
• The participant has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to that of IMC-3G3
• The participant has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure,uncontrolled hypertension, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• The participant has a history of another primary cancer, with the exception of: a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c) other primary solid tumor treated with curative intent and no known active disease present and no treatment administered during the last 3 years prior to randomization
• The participant is pregnant or lactating
• The participant has unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 6 months prior to randomization
• The participant has participated in clinical trials of experimental agents within 28 days prior to randomization
• The participant has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders
• The participant has a serious or nonhealing active wound, ulcer, or bone fracture
• The participant has known human immunodeficiency virus positivity

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (6)

ImClone Investigational Site

Joliet, Illinois, 60435, United States

Location

ImClone Investigational Site

Indianapolis, Indiana, 46202, United States

Location

ImClone Investigational Site

Baltimore, Maryland, 21237, United States

Location

ImClone Investigational Site

Boston, Massachusetts, 02114-2621, United States

Location

ImClone Investigational Site

Detroit, Michigan, 48202, United States

Location

ImClone Investigational Site

Charlotte, North Carolina, 28204, United States

Location

Related Publications (2)

• Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

  PMID: 37185961 DERIVED

• McGuire WP, Penson RT, Gore M, Herraez AC, Peterson P, Shahir A, Ilaria R Jr. Randomized phase II study of the PDGFRalpha antibody olaratumab plus liposomal doxorubicin versus liposomal doxorubicin alone in patients with platinum-refractory or platinum-resistant advanced ovarian cancer. BMC Cancer. 2018 Dec 27;18(1):1292. doi: 10.1186/s12885-018-5198-4.

  PMID: 30591028 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Neoplasms

Interventions

olaratumab; liposomal doxorubicin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2009
• First Posted: June 4, 2009
• Study Start: June 1, 2009
• Primary Completion: October 1, 2011
• Study Completion: February 1, 2014
• Last Updated: September 26, 2019
• Results First Posted: April 14, 2017

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

US (6)