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Ovarian NeoplasmsPhase 2NCT00913835

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

A Phase 2 study testing Olaratumab and liposomal doxorubicin in people with Ovarian Neoplasms, run by Eli Lilly and Company at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Ovarian Neoplasms
What is being tested?
Olaratumab and liposomal doxorubicin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
125 participants
Where
6 sitesUnited States
Study dates
Jun 2009to Feb 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 recovered to Grade ≤1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v3.0) from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted therapies for ovarian cancer, with the exception of alopecia or peripheral neuropathy (which must have resolved to ≤Grade 2). The exceptions for such effects are allowed lab values of ≤Grade 2 specified elsewhere in these inclusion criteria
  • The participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤1 at study entry
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  • 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

Who cannot join

  • 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
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  • 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 ongoing side effects ≥Grade 2 due to agents administered more than 28 days prior to randomization. The exceptions for such effects are allowed lab values and toxicities of ≤Grade 2, specified in the inclusion criteria
  • 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
  • The participant had a major surgical procedure, an open biopsy, or significant traumatic injury within 28 days prior to randomization
  • The participant has received an anthracycline for any indication in the past

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • ImClone Investigational Site

    Baltimore, Maryland, 21237

  • ImClone Investigational Site

    Boston, Massachusetts, 02114-2621

  • ImClone Investigational Site

    Charlotte, North Carolina, 28204

  • ImClone Investigational Site

    Detroit, Michigan, 48202

  • ImClone Investigational Site

    Indianapolis, Indiana, 46202

  • ImClone Investigational Site

    Joliet, Illinois, 60435

Other trials in United States

About this study

Official title: Randomized Phase 2 Trial Investigating Liposomal Doxorubicin With or Without Anti-Platelet Derived Growth Factor Receptor-Alpha (PDGFRα) Monoclonal Antibody IMC-3G3 in Patients With Platinum-Refractory or Platinum-Resistant Advanced Ovarian Cancer

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.

Read the detailed description

The primary objective of this study is to evaluate the progression-free survival (PFS) in participants with platinum-refractory or platinum-resistant advanced ovarian cancer when treated with the monoclonal antibody Olaratumab in combination with liposomal doxorubicin versus liposomal doxorubicin alone.

Being tested
Olaratumab, liposomal doxorubicin
Keywords
Liposomal Doxorubicin, IMC-3G3, 3G3, Platinum resistant, Platinum refractory, Ovary, Neoplasm, PDGFr
Medical subject headings
Ovarian Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OlaratumabBiological

    Also called LY3012207, IMC-3G3

    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

  • liposomal doxorubicinDrug

    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

Study groups in NCT00913835
Study groupRoleWhat they receive
Olaratumab and Liposomal DoxorubicinExperimentalOlaratumab and Liposomal Doxorubicin
Receives: Biological: Olaratumab; Drug: liposomal doxorubicin
Liposomal Doxorubicin: Optional Olaratumab MonotherapyActive comparatorLiposomal Doxorubicin Monotherapy until disease progression. Upon disease progression the participant had the option to receive Olaratumab monotherapy.
Receives: Biological: Olaratumab; Drug: liposomal doxorubicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (12)

  1. Overall Survival (OS)

    OS is defined as the time from first day of therapy to the date of death from any cause. Participants who were alive at the end of the follow-up period or were lost to follow-up, OS was censored on the last date the participant was known to be alive.

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

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

    The percentage of participants with a best overall response of confirmed CR or PR defined using RECIST v1.0 criteria. CR is the disappearance of all target and non-target lesions and normalization of cancer antigen-125 (CA-125) levels. PR is defined as having a ≥30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. The percentage of participants with objective response was calculated as: (number of participants whose best overall response of CR or PR/number of participants treated) * 100.

    Measured: Randomization to PD (Up to 35 Months)

  3. Median Duration of Response

    Duration of response is the interval from the date of initial CR or PR until the first date criteria for PD is met using RECIST v1.0 criteria, or initiation of other (or additional) antitumor therapy is first reported, or death due to any cause. CR is the disappearance of all target and non-target lesions and the normalization of tumor marker levels. PR is a ≥30% decrease in the sum of the LD of target lesions without new lesions and progression of non-target lesions. PD is a ≥20% increase in the sum of the LD of target lesions and/or unequivocal progression of existing non-target lesions and/or detection of 1 or more new lesions. Participants who did not relapse were censored on the day of their last tumor assessment.

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

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

    Reported are the number of participants with clinically significant events, defined as serious AEs (SAEs) and other non-serious AEs regardless of causality and those who died during treatment and during the 30-day post-dose follow-up. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module of this report.

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

  5. Percentage of Participants With Anti-Olaratumab Antibodies

    Participants with Treatment Emergent (TE) anti-olaratumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.

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

  6. PFS of Participants Who Received Olaratumab After Liposomal Doxorubicin Monotherapy (Descriptive Statistics for Safety and Efficacy for Participants Who Continue on Olaratumab Monotherapy Following Disease Progression on Liposomal Doxorubicin Monotherapy)

    PFS is defined as the time from start of Olaratumab monotherapy to the first evidence of progression as defined by RECIST v1.0 criteria or death from any cause. 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.

    Measured: From Start of Olaratumab Monotherapy to PD or Date of Death (Up to 20 Weeks)

  7. Area Under the Curve (AUC) of Olaratumab

    Measured: Prior to and 1 Hour (h) After Olaratumab Infusion in Cycles 1, 2, and 4 and 48 h or 72 h, 144 h, 240 h or 264 h and 336 h Post-dose in Cycles 1 and 4 (28-day Cycles)

  8. Maximum Concentration (Cmax) of Olaratumab

    Measured: Prior to and 1 h after Olaratumab Infusion in Cycles 1, 2, and 4 and 48 h or 72 h, 144 h, 240 h or 264 h and 336 h Post-dose in Cycles 1 and 4 (28-day Cycles)

  9. Half-life (t1/2) of Olaratumab

    The time it takes to reduce the concentration of Olaratumab in the plasma by 50%.

    Measured: Prior to and 1 h after Olaratumab Infusion in Cycles 1, 2, and 4 and 48 h or 72 h, 144 h, 240 h or 264 h and 336 h Post-dose in Cycles 1 and 4 (28-day Cycles)

  10. Clearance (CL) of Olaratumab

    CL is the volume of serum cleared of Olaratumab per unit of time after a single dose of Olaratumab

    Measured: Prior to and 1 h after Olaratumab Infusion in Cycles 1, 2, and 4 and 48 h or 72 h, 144 h, 240 h or 264 h and 336 h Post-dose in Cycles 1 and 4 (28-day Cycles)

  11. Apparent Volume of Distribution (Vss) of Olaratumab

    Vss is an estimate of drug distribution independent of the elimination process and is proportional to the amount of drug in the body versus the drug plasma concentration at steady-state.

    Measured: Prior to and 1 h after Olaratumab Infusion in Cycles 1, 2, and 4 and 48 h or 72 h, 144 h, 240 h or 264 h and 336 h Post-dose in Cycles 1 and 4 (28-day Cycles)

  12. PFS for Participants Who Had Tissue Samples for Platelet Derived Growth Factor Receptor Alpha (PDGFRα) Expression Determined by Immunohistochemistry (IHC) (Association Between PDGFRα Tumor Expression and PFS)

    PFS is defined as the time from the day of randomization to the first evidence of progression as defined by RECIST v1.0 criteria or death from any cause. PD is a 20% increase over the smallest sum of target lesions or new lesions. Participants who died without a 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. PDGFRα protein expression at baseline in tumor cells is determined by IHC using H-Scores and a cut point of 0. Participants were considered to have a high relative expression when H-Score is >0 and a low relative expression when H-Score=0. H-Score was calculated by summing the percentage of cell staining at each intensity multiplied by the weighted intensity of staining. Staining intensity: 0 (no staining), 1+ (weak staining), 2+ (medium staining), 3+ (strongest staining). H-Scores could range from 0-300.

    Measured: Randomization to PD or Date of Death (Up to 130 Weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jun 2009 (estimated)
  2. Study startJun 2009
  3. Primary completionOct 2011
  4. Study completionFeb 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
125 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00913835
Sponsor's protocol ID
13899
Other IDs
2009-009035-30, CP15-0802, I5B-IE-JGDA, 2009
Status last verified
Sep 2019
First submitted
2 Jun 2009
Last updated
26 Sep 2019
Data monitoring committee
Yes
Individual data sharing
Yes: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Publications

  • 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.

    PubMed 37185961

  • 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.

    PubMed 30591028

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Olaratumab and liposomal doxorubicin in people with Ovarian Neoplasms, run by Eli Lilly and Company at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (PFS) (time frame: Randomization to Progressive Disease (PD) or Date of Death (Up to 35 Months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00913835, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2019.

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