Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Doxorubicin

Liposomal doxorubicin

Immunoglobulins

Mitogens

Olaratumab

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

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

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

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

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)

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.

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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

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

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.

Eli Lilly and Company

20 mg/kg of Olaratumab was administered as an IV infusion every 2 weeks (14 days) until there was evidence of PD or development of unacceptable toxicity up to 130 weeks.

40 mg/m² of liposomal doxorubicin was administered according to the manufacturer's instructions every 4 weeks (28 days) until there was evidence of PD or development of unacceptable toxicity.

Olaratumab and Liposomal Doxorubicin

40 mg/m² of liposomal doxorubicin was administered according to the manufacturer's instructions every 4 weeks (28 days). Treatment continued until there was evidence of PD or development of unacceptable toxicity up to 130 weeks.

Upon disease progression the participant had the option to receive Olaratumab monotherapy.

Liposomal Doxorubicin

40 mg/m² of liposomal doxorubicin was administered according to the manufacturer's instructions every 4 weeks (28 days). Treatment continued until there was evidence of PD or development of unacceptable toxicity followed by 20 mg/kg of Olaratumab administered as an IV infusion every 2 weeks (14 days) until there was evidence of PD or development of unacceptable toxicity up to 130 weeks.

Liposomal Doxorubicin: Optional Olaratumab Monotherapy

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Asian

Black or African American

Native Hawaiian of Other Pacific Islander

White

Other

Race/Ethnicity, Customized

United States

United Kingdom

Spain

Region of Enrollment

0-Fully Active

1-ambulatory, able to do light/sedentary nature

ECOG PS classified participants according to their functional impairment.

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

Platinum Refractory

Platinum Resistant

Participants reaction to prior platinum treatment.

Stratification Factor

Modified Intent to Treat (mITT) Population: All participants who were randomized and received any quantity of study drug.

Chief Medical Officer

Modified Intent to Treat (mITT) Population: All randomized participants who received any amount of study drug. Participants censored: Olaratumab=13, Liposomal Doxorubicin=14.

Progression-Free Survival (PFS)

mITT Population: All randomized participants who received any amount of study drug. Participants censored: Olaratumab=21, Liposomal Doxorubicin=23.

Overall Survival (OS)

mITT Population: All randomized participants who received any amount of study drug.

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

All participants who achieved CR or PR. Participants censored: Olaratumab=2, Liposomal Doxorubicin=4.

Median Duration of Response

SAEs

Other Non-SAEs

Deaths on treatment or within 30 days of last dose

40 mg/m² of liposomal doxorubicin was administered according to the manufacturer's instructions every 4 weeks (28 days). Treatment continued until there was evidence of PD or development of unacceptable toxicity up to 130 weeks.

Upon disease progression the participant had the option to receive Olaratumab monotherapy..

All randomized participants who received any amount of study drug.

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

All randomized participants who received at least one dose of study drug and had evaluable baseline and evaluable post-baseline antibody data.

Percentage of Participants With Anti-Olaratumab Antibodies

Participants who received Olaratumab treatment after PD on liposomal doxorubicin monotherapy. Participants censored=4

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)

Zero participants were analyzed. An insufficient amount of samples were collected to derive this measure.

Area Under the Curve (AUC) of Olaratumab

Maximum Concentration (Cmax) of Olaratumab

Half-life (t1/2) of Olaratumab

Clearance (CL) of Olaratumab

40 mg/m² of liposomal doxorubicin was administered according to the manufacturer's instructions every 4 weeks (28 days). Treatment continued until there was evidence of PD or development Olaratumab administered as an IV infusion every 2 weeks (14 days) until there was evidence of PD or development of unacceptable toxicity up to 130 weeks.

Liposomal Doxorubicin: Optional Olaratumab Treatment

Apparent Volume of Distribution (Vss) of Olaratumab

High Expression (n=41, 36)

Low Expression (n=13,11)

All participants who had evaluable PDGFRα results.

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)

20 milligrams per kilogram (mg/kg) of Olaratumab was administered as an intravenous (IV) infusion every 2 weeks (14 days) until there was evidence of progressive disease (PD) or development of unacceptable toxicity.

40 milligrams per square meter (mg/m²) of liposomal doxorubicin was administered according to the manufacturer's instructions every 4 weeks (28 days) until there was evidence of PD or development of unacceptable toxicity.

Olaratumab + Liposomal Doxorubicin

40 mg/m² of liposomal doxorubicin was administered according to the manufacturer's instructions every 4 weeks (28 days). Treatment continued until there is evidence of PD or development of unacceptable toxicity up to 130 weeks.

Upon disease progression the participant had the option to receive Olaratumab monotherapy.

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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial