Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Angiogenesis Inhibitors

Sunitinib

Trebananib

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Trebananib 10 mg/kg intravenously (IV) once weekly (QW) plus sunitinib 50 mg orally (PO) once daily (QD) 4 weeks on/2 weeks off

Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off

Sunitinib will be administered 50 mg QD and is considered to be the background therapy as it is licensed for treatment of reneal cell cancer (RCC) and will be administered to all participants.

Administered until a participant develops disease progression, clinical progression, unacceptable toxicity, withdraws consent, or death.

This phase 2 study is an open-label, multi-center study to determine the safety and tolerability of AMG 386 in combination with sunitinib in the treatment of subjects with metastatic renal cell carcinoma.

AMG 386 Phase 2 Open-Label Renal Cell Carcinoma (RCC) Study 1st Line or After Cytokine Failure in Combination With Sunitinib

Phase 2 Open-Label, Multi-Center Study to Evaluate the Safety and Efficacy of Sunitinib Malate in Combination With AMG 386 as First Line or Second Line Therapy for Subjects With Metastatic Renal Cell Carcinoma

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

AE: any untoward medical occurrence that does not necessarily have a causal relationship with treatment. SAE: an AE that: is fatal; is life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an other significant medical hazard. Treatment-emergent AEs (TEAEs) are those that occurred after the first administration of study drug through 30 days after the last study drug administration. Severity was graded according to Common Terminology Criteria (CTCAE) version 3.0, as grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death).

A trebananib dose was considered delayed if it was administered 11 or more days from the previous trebananib infusion. A sunitinib dose was considered delayed if it was administered 3 or more days from the previous dose, except during holidays.

Participants who had a sunitinib dose modification within 12 weeks from their first dose due to adverse event, laboratory toxicity, or laboratory toxicity and adverse event.

Severity was graded according to Common Terminology Criteria (CTCAE) version 3.0, as grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death).

ORR was defined as the percentage of participants with either a confirmed complete response (CR) or partial response (PR) per modified Response Evaluation Criteria in Solid Tumor (RECIST) criteria (responder). A confirmed CR requires 2 consecutive assessments of CR at least 28 days apart. A confirmed PR requires 2 consecutive assessments at least 28 days apart of PR or CR. All participants who did not meet the criteria for an objective response by the analysis cutoff date were considered non responders.

DOR was calculated as the time from the first confirmed objective response to first observed disease progression per modified RECIST v. 1.0 criteria or death due to any cause. DOR was calculated only for participants who had an objective response. Objective response was defined as either a confirmed CR or PR per modified RECIST criteria. A confirmed CR required 2 consecutive assessments of CR at least 28 days apart. A confirmed PR required 2 consecutive assessments at least 28 days apart of PR or CR.

Participants not meeting criteria for progression by the analysis data cutoff date were censored at their last evaluable radiographical disease assessment date.

DCR was defined as the percentage of participants with confirmed CR or PR or stable disease (SD), as defined by modified RECIST v1.0 criteria. A confirmed CR required 2 consecutive assessments of CR at least 28 days apart. A confirmed PR requires 2 consecutive assessments at least 28 days apart of PR or CR. CR or PR was confirmed at least 28 days after the criteria for response were first met. A response assessment of PR or CR that was not subsequently confirmed at least 4 weeks later were included as SD.

PFS was defined as the time from enrollment date to date of disease progression (ie, radiographic progression) per modified RECIST v 1.0 criteria or death. Radiological imaging to assess disease status was performed until participants developed disease progression. Events of radiographic progression per modified RECIST 1.0 that occurred after initiation of subsequent anticancer therapy were not considered PFS events. Deaths occurring after initiation of subsequent anticancer therapy were considered PFS events.

Participants not meeting criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.

The time from enrollment date to date of death. Participants who had not died by the analysis data cutoff date were censored at their last contact date.

Change in tumor burden was evaluated by the maximum percent reduction from baseline in the SLD of target lesions.

Transient positive results were defined as a positive post-baseline result followed by a negative result at the participant's last time point tested within the study period.

Amgen

Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. Other adverse events shows non-serious occurrences of adverse event that exceed the indicated frequency threshold.

Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off

Trebananib 10 mg/kg + Sunitinib

Trebananib 15 mg/kg + Sunitinib

Total

< 65 years

>= 65 years

< 75 years

>= 75 years

Age, Customized

Sex: Female, Male

White or Caucasian

Black or African American

Hispanic or Latino

Asian

Japanese

American Indian or Alaska Native

Native Hawaiian or Other Pacific Islander

Aborigine

Other, Not Specified

Race/Ethnicity, Customized

Study Director

TEAEs, All

TEAEs, Grade ≥ 3

TEAEs, Grade ≥ 4

TEAEs, Fatal AEs

TEAEs, SAEs

TEAEs Leading to (→) DC of Trebananib

TEAEs → DC of Trebananib, Serious

TEAEs → DC of Trebananib, Non-Serious

TEAEs → DC of Sunitinib

TEAEs → DC of Sunitinib, Serious

TEAEs → DC of Sunitinib, Non-Serious

TEAEs → DC of All Treatment

TEAEs → DC of All Treatment, Serious

TEAEs → DC of All Treatment, Non-Serious

Treatment-Related (TR) TEAEs, All

TR TEAEs, Grade ≥ 3

TR TEAEs, Grade ≥ 4

TR TEAEs, Fatal AEs

TR TEAEs, SAEs

TR TEAEs → DC of Trebananib

TR TEAEs → DC of Trebananib, Serious

TR TEAEs → DC of Trebananib, Non-Serious

TR TEAEs → DC of Sunitinib

TR TEAEs → DC of Sunitinib, Serious

TR TEAEs → DC of Sunitinib, Non-Serious

TR TEAEs → DC of All Treatment

TR TEAEs → DC of All Treatment, Serious

TR TEAEs → DC of All Treatment, Non-Serious

Trebananib-Related (TrR) TEAEs, All

TrR TEAEs, Grade ≥ 3

TrR TEAEs, Grade ≥ 4

TrR TEAEs, Fatal AEs

TrR TEAEs, SAEs

TrR TEAEs → DC of Trebananib

TrR TEAEs → DC of Trebananib, Serious

TrR TEAEs → DC of Trebananib, Non-Serious

TrR TEAEs → DC of Sunitinib

TrR TEAEs → DC of Sunitinib, Serious

TrR TEAEs → DC of Sunitinib, Non-Serious

TrR TEAEs → DC of All Treatment

TrR TEAEs → DC of All Treatment, Serious

TrR TEAEs → DC of All Treatment, Non-Serious

Sunitinib-Related (SR) TEAEs, All

SR TEAEs, Grade ≥ 3

SR TEAEs, Grade ≥ 4

SR TEAEs, Fatal AEs

SR TEAEs, SAEs

SR TEAEs → DC of Trebananib

SR TEAEs → DC of Trebananib, Serious

SR TEAEs → DC of Trebananib, Non-Serious

SR TEAEs → DC Sunitinib

SR TEAEs → DC of Sunitinib, Serious

SR TEAEs → DC of Sunitinib, Non-Serious

SR TEAEs → DC of All Treatment

SR TEAEs → DC of All Treatment, Serious

SR TEAEs → DC of All Treatment, Non-Serious

Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs)

Trebananib Dose Delays

Sunitinib Dose Delays

Safety Analysis Set: participants who received at least 1 dose of trebananib and 1 dose of sunitinib.

Number of Participants With Dose Delays Due to Adverse Events

Any Dose Modification (DM)

DM Due to Adverse Event

DM Due to Laboratory Toxicity

DM Due to Laboratory Toxicity and Adverse Event

Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose

Alanine Aminotransferase, Above Normal (AN)

Albumin, Below Normal (BN)

Alkaline Phosphatase, AN

Amylase, AN

Aspartate Aminotransferase, AN

Glucose, AN

Glucose, BN

Lipase, AN

Magnesium, BN

Phosphorus, BN

Potassium, BN

Sodium, BN

Total Bilirubin, AN

Absolute Neutrophil Count, BN

Hemoglobin, BN

Lymphocytes, BN

Partial Thromboplastin Time, AN

Platelets, BN

Total Neutrophils, BN

Safety Aanalysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib.

Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values

Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. Participants with baseline measureable disease.

Objective Response Rate (ORR)

Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. Participants with an objective response.

Kaplan-Meier Estimate: Duration of Response (DOR)

Disease Control Rate (DCR)

Kaplan-Meier Estimate: Progression Free Survival (PFS)

Kaplan-Meier Estimate: Overall Survival (OS)

Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. Participants with baseline measureable disease and non-missing baseline and post-baseline data.

Maximum Percent Reduction From Baseline in the Sum of the Longest Diameters (SLD) of Target Lesions From Baseline to Post-Baseline Nadir

Week 1

Week 4

Week 7

Week 10

Week 13

Week 22

Week 34

Week 46

Week 58

Week 70

Week 82

Week 94

Week 106

Safety Follow-Up

Pharmacokinetics Analysis Set: participants with evaluable concentration data at given time point.

Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time

Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time

Week 16

Pharmacokinetics Analysis Set: participants with evaluable concentration data at given time point. Per protocol, this outcome measure evaluated a sub-group of participants at selected sites outside of Europe.

Pharmacokinetic Parameter: Cmin for Sunitinib Over Time

Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time

Binding Antibody Positive Post-Baseline (PBL)

Binding Antibody Positive PBL, Transient

Neutralizing Antibody Positive PBL

Neutralizing Antibody Positive PBL, Transient

Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. Participants with a post-baseline result and a negative result or no result at baseline.

Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline

Overall Study

Spots Global Cancer Trial Database for AMG 386 Phase 2 Open-Label Renal Cell Carcinoma (RCC) Study 1st Line or After Cytokine Failure in Combination With Sunitinib

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial