Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Taxane

Ramucirumab

Antimetabolites

Angiogenesis Inhibitors

Growth Inhibitors

Cycles repeat until disease progression, the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant.

Crossover Study:

\* At the discretion of the investigator, participants will be eligible to receive either ramucirumab DP or Icrucumab (IMC-18F1) in combination with capecitabine, after radiographic disease progression while on capecitabine. The investigator will decide which investigational product will be given.

Cycles repeat every 21 days until disease progression, the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant.

10 mg/kg I.V.

Day 1 of every-21-day cycle

Ramucirumab DP

12 mg/kg I.V.

Days 1 and 8 of every-21-day cycle

IMC-18F1

1000 mg/m\^2 orally

Twice a day for 14 days

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)

An open-label, multicenter, randomized, Phase 2 trial in which participant with unresectable, locally advanced or metastatic breast cancer who have been previously treated with anthracycline and taxane therapy receive ramucirumab DP or Icrucumab (IMC-18F1) administered on an every-21-day cycle (in combination with oral capecitabine therapy; capecitabine is administered twice a day on Days 1-14 of each cycle). Approximately 150 participants will be randomized in a 1:1:1 ratio to either ramucirumab DP or Icrucumab (IMC-18F1) in combination with capecitabine (Arm A and Arm B, respectively) or capecitabine monotherapy (Arm C). Randomization will be stratified by triple-negative receptor status (estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor-2 \[HER2/neu\]-negative) (yes/no) and receipt of prior antiangiogenic therapy.

Treatment with the study medication(s) will continue until disease progression, the development of unacceptable toxicity, noncompliance or withdrawal of consent by the participant, or investigator decision. Capecitabine dose reductions in the setting of significant myelosuppression, hand-and-foot syndrome, or diarrhea will be required.

Study of Icrucumab (IMC-18F1) or Ramucirumab Drug Product (DP) in Combination With Capecitabine or Capecitabine on Previously Treated Breast Cancer Patients

An Open-Label, Multicenter, Randomized Phase 2 Study Evaluating the Safety and Efficacy of Ramucirumab (IMC-1121B) Drug Product or Icrucumab (IMC-18F1) in Combination With Capecitabine or Capecitabine Monotherapy, in Unresectable, Locally Advanced or Metastatic Breast Cancer Patients Previously Treated With Anthracycline and Taxane Therapy

Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com.

This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.

PFS is defined as the time from the date of randomization until the date of objectively determined progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death from any cause, whichever is first. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 millimeter (mm) and the appearance of ≥1 new lesions was progression. Participants who did not progress, were lost to follow-up, or had missed 2 or more scheduled tumor assessments were censored at the day of their last adequate tumor assessment.

Overall survival is defined as the time from the date of randomization to the date of death from any cause. If the participant is alive at the end of the follow-up period or is lost to follow-up, OS will be censored on the last date the participant is known to be alive.

The ORR is the number of all participants with Partial Response (PR) or Complete Response (CR) according to RECIST v1.1 from the start of the treatment until disease progression/recurrence. CR was defined as the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to \<10 mm. PR was defined as ≥30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 mm and the appearance of ≥1 new lesions was progression.

Duration of response is measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that the criteria for progressive disease (PD) is met (taking as a reference for PD that smallest measurement recorded since the treatment started), or death, is objectively documented.CR was defined as the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to \<10 mm. PR was defined as ≥30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter.PD defined as ≥20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Sum must also have demonstrated an absolute increase of ≥5 mm, or the appearance of 1 or more new lesions was considered progression.

Adverse event (AE) will be regarded as treatment-emergent if onset date occurs any time on or after the administration of the first dose of study treatment up to 30 days after the last dose of study treatment (or up to any time if related to study treatment); or it occurs prior to first dose date and worsens while on therapy or up to 30 days after the last dose of study treatment (or up to any time if related to study treatment).

A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

SAE was defined as any untoward medical occurrence that at any dose:

Resulted in death; Was life-threatening; Required inpatient hospitalization or caused prolongation of existing hospitalization; Resulted in persistent or significant disability/incapacity; Was a congenital anomaly/birth defect; Required intervention to prevent permanent impairment/damage; Was an important medical event (defined as a medical event that may not have been immediately life-threatening or resulted in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the participant or may require intervention to prevent one of the other serious outcomes listed in the definition above).

A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Minimum Concentration (Cmin) Ramucirumab Drug Product (DP) or Icrucumab.

Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity of Ramucirumab and Icrucumab.

Terminal half-life (t½) of Ramucirumab and Icrucumab.

Clearance (Cl) of Ramucirumab and Icrucumab.

Volume of Distribution at Steady State (Vss) of Ramucirumab and Icrucumab.

Eli Lilly and Company

All randomized participants who received at least one dose of study drug.

Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per meter square (mg/m\*2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Ramucirumab + Capecitabine

Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 milligram per meter square (mg/m\*2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Icrucumab + Capecitabine

Participants received 1000 mg/m\*2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Crossover to Ramucirumab DP + Capecitabine

Crossover to Icrucumab + Capecitabine

Participants received 10 mg/kg Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 mg/m\^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m\^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants received 1000 mg/m\^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

After radiographic diseases progression while on Capecitabine, participants were crossed-over to either Ramucirumab or Icrucumab;

Participants crossed-over to Ramucirumab + Capecitabine had received 10 mg/kg Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 mg/m\^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants crossed-over to Icrucumab + Capecitabine received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m\^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Chief Medical Officer

Kaplan-Meier methodology estimated median PFS

Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per square meter (mg/m\^2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

All randomized participants who received at least one dose of study drug; Censored participants: Ramucirumab + Capecitabine = 12; Icrucumab + Capecitabine = 11; Capecitabine = 7

Progression-Free Survival (PFS)

All randomized participants who received at least one dose of study drug; censored participants: Ramucirumab + Capecitabine = 21; Icrucumab + Capecitabine = 17; Capecitabine = 22 Participants were analyzed as per the randomization.

Overall Survival (OS)

Percentage of Participants With Objective Response Rate (ORR)

All randomized participants who received at least one dose of study drug and had CR/PR.

Duration of Response

Number of Participants With Adverse Events (AEs)

Number of Participants With Serious Adverse Events (SAEs)

For ramucirumab, all randomized participants who received at least one dose of study drug \& had evaluable pharmacokinetic (PK) samples.

For icrucumab, zero participants analyzed as reliable PK parameters could not be estimated using non-compartmental PK analysis due to insufficient number of samples.

Maximum Concentration (Cmax) Ramucirumab Drug Product (DP) or Icrucumab

Cycle 2

Cycle 4

Cycle 6

Cycle 8

Cycle 10

Cycle 12

Cycle 14

Cycle 16

Cycle 18

Cycle 22

Minimum Concentration (Cmin) Ramucirumab Drug Product (DP) or Icrucumab

Area Under the Concentration Versus Time Curve From Time Zero to Infinity of Ramucirumab or Icrucumab

Terminal Half-life (t½) of Ramucirumab or Icrucumab

Clearance (Cl) of Ramucirumab or Icrucumab

Volume of Distribution at Steady State (Vss) of Ramucirumab or Icrucumab

Treatment emergent antibody

Neutralizing antibody

For ramucirumab, Aall randomized participants who received at least one dose of study drug and had evaluable serum samples for antibody assessment.

For icrucumab, zero participants analyzed as antibody assessment data was not collected for Icrucumab.

Number of Participants With Anti-Ramucirumab and Anti-Icrucumab Antibodies

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Rare Diseases

Carcinoma

Urinary Bladder Neoplasms

Carcinoma, Renal Cell

Carcinoma, Transitional Cell

Disease Progression

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Urethral Cancer

Docetaxel

Tubulin Modulators

Antimitotic Agents

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: 75 milligram/square meter (mg/m2) on Day 1 of each 21-day cycle

Ramucirumab (DP): 10 milligram/kilogram (mg/kg) intravenous (IV) on day 1 of each 21-day cycle

12 mg/kg I.V. on day 1 and Day 8 of each 21-day cycle

Icrucumab

This multicenter trial will enroll participants with metastatic transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis who have had disease progression on first-line platinum-based chemotherapy regimens. Participants will be enrolled into 1 of 3 treatment arms: docetaxel; docetaxel and ramucirumab; or docetaxel and icrucumab.

Study of Ramucirumab or Icrucumab (IMC-18F1) With Docetaxel or Docetaxel Alone as Second-Line Therapy in Participants With Bladder,Urethra, Ureter, or Renal Pelvis Carcinoma

An Open-Label, Multicenter, Randomized Phase 2 Study Evaluating the Safety and Efficacy of Docetaxel in Combination With Ramucirumab (IMC-1121B) Drug Product or IMC-18F1 or Without Investigational Therapy as Second-line Therapy in Patients With Locally Advanced or Metastatic Transitional Cell Carcinoma of the Bladder, Urethra, Ureter, or Renal Pelvis Following Disease Progression on First-line Platinum-based Therapy

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 time was the time from randomization until the date of objectively determined progressive disease (PD) or death due to any cause, whichever occurred first. According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), PD was at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the 20% relative increase, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions was also considered progression. Participants without objectively determined PD who were alive at the end of the follow-up period (or lost to follow-up) were censored on the date of the participant's last complete radiographic tumor assessment; if no baseline or post-baseline radiologic assessment was available, the participant was censored at the date of randomization.

Participants achieved an objective response if they had a best overall response of partial response (PR) or complete response (CR). According to RECIST v1.1, PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter; CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to \<10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels \[if tumor markers were initially above the upper limit of normal (ULN)\]. The percentage of participants who achieved an objective response=(number of participants with CR or PR)/(number of participants assessed)\*100.

The duration of response was measured from the time measurement criteria were first met for a CR or PR (whichever was first recorded) until the first date of objectively documented progressive disease (taking as a reference for progressive disease the smallest measurement recorded since randomization) or the date of death, whichever occurred first. Data for participants who did not relapse or die were censored at the day of their last adequate tumor assessment. Duration of response was estimated by the Kaplan-Meier method.

A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Number of participants with at least one positive titer treatment emergent antibody positive neutralizing antibody detecting. A sample will be considered positive for anti-Ramucirumab antibodies if it exhibits a post-baseline antibody level exceeding the normal anti-Ramucirumab antibody level seen in healthy untreated individuals.

A sample will be considered positive for anti-Icrucumab antibodies if it exhibits a post-baseline antibody level exceeding the normal anti-IMC-Icrucumab antibody level seen in healthy untreated individuals.

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: Docetaxel: 75 mg/m2 on Day 1 of each 21-day cycle

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: Docetaxel: 75 mg/m2 on Day 1 of each 21-day cycle

Ramucirumab DP: Ramucirumab (DP): 10 mg/kg IV on day 1 of each 21-day cycle

Docetaxel + Ramucirumab DP

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: Docetaxel: 75 mg/m2 on Day 1 of each 21-day cycle

Icrucumab: 12 mg/kg IV on day 1 and Day 8 of each 21-day cycle

Docetaxel + Icrucumab

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: 75 mg/m2 on Day 1 of each 21-day cycle

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: 75 mg/m2 on Day 1 of each 21-day cycle

Ramucirumab (DP): 10 mg/kg IV on day 1 of each 21-day cycle

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: 75 mg/m2 on Day 1 of each 21-day cycle

Icrucumab: 12 mg/kg IV on day 1 and Day 8 of each 21-day cycle

Race (NIH/OMB)

Canada

United States

Region of Enrollment

All randomized participants who received at least 1 dose of study drug.

All randomized participants who received at least one dose of study drug. Participants censored: docetaxel arm = 40; docetaxel and ramucirumab arm = 34; docetaxel and Icrucumab arm = 41.

All randomized participants who received one dose of study drug.

Percentage of Participants Achieving Objective Response Rate (ORR)

All randomized participants received one dose of study drug and had CR or PR.

Any AE

Any SAE

Cycle 1

Cycle 3

All randomized participants who received at least one dose of study drug and had evaluable PK data for Ramucirumab and there was no PK data for Docetaxel arm.

Pharmacokinetics (PK) Maximum Concentration (Cmax) Ramucirumab

PK: Minimum Concentration (Cmin) Ramucirumab

Cycle 1 Cmax

Cycle 3 Cmax

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: 75 mg/m2 on Day 1 of each 21-day cycle

Icrucumab: 12 mg/kg IV on Day 1 and Day 8 of each 21-day cycle

All randomized participants who received at least one dose of study drug and had evaluable PK data for Icrucumab and there was no PK data for Docetaxel arm.

PK: Cmax Icrucumab

Day 1 Cycle 2

Day 1 Cycle 3

PK: Cmin Icrucumab

All randomized participants who received at least one dose of study drug and had baseline and post baseline anti-ramucirumab antibodies.

Number of Participants With Serum Anti-Ramucirumab Antibody Assessment

Zero participants analyzed. Data not collected.

Number of Participants With Serum Anti-Icrucumab Antibody Assessment

Pharmacodynamics (PD): Change in Circulating Levels of Placental Growth Factor (PlGF)

PD: Change in Circulating Levels of Vascular Endothelial Growth Factor-A (VEGF-A)

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: Docetaxel: 75 milligram/square meter (mg/m2) on Day 1 of each 21-day cycle

PD: Change in Circulating Levels of Vascular Endothelial Growth Factor-B (VEGF-B)

PD: Change in Circulating Levels of Soluble Vascular Endothelial Growth Factor-1 (VEGFR-1)

PD: Change in Circulating Levels of Soluble Vascular Endothelial Growth Factor-2 (VEGFR-2)

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: 75 milligram/square meter (mg/m2) on Day 1 of each 21-day cycle

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Icrucumab (IMC-18F1) or Ramucirumab Drug Product (DP) in Combination With Capecitabine or Capecitabine on Previously Treated Breast Cancer Patients	NCT01234402	Breast Cancer	Ramucirumab DP IMC-18F1 Capecitabine	18 Years -	Eli Lilly and Company
Study of Ramucirumab or Icrucumab (IMC-18F1) With Docetaxel or Docetaxel Alone as Second-Line Therapy in Participants With Bladder,Urethra, Ureter, or Renal Pelvis Carcinoma	NCT01282463	Carcinoma of Ur... Urethral Carcin... Carcinoma of Ur... Carcinoma of Re...	Docetaxel Ramucirumab DP Icrucumab	18 Years -	Eli Lilly and Company

Spots Global Cancer Trial Database for ramucirumab dp