Neoplasms

All Conditions

Symptoms and General Pathology

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Carboplatin

Cetuximab

Cisplatin

Immunoglobulins

Antineoplastic Agents, Immunological

All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin) in Period 1 - Initial phase of the trial.

Participants deriving clinical benefit enter Period 2 - Extension phase, during which they continue to receive patritumab with cetuximab, but not platinum-based therapy.

Patritumab initial loading dose is 18 mg/kg IV over 60 minutes, followed in Cycle 2 and beyond with a maintenance dose of 9 mg/kg IV over 60 minutes (+/- 10 minutes) every 3 weeks. Infusion time can be extended to a maximum of 120 minutes for participants unable to tolerate the 60-minute infusion.

Patritumab

Cetuximab initial dose at 400 mg/m2 IV as a 2-hour infusion, followed by 250 mg/m2 IV over 60 minutes weekly.

Cisplatin is given as an IV infusion, over 1 hour, 1 hour after the cetuximab infusion, every 3 weeks up to a maximum of 6 cycles (with standard pre- or post-treatment therapies at the investigator's discretion).

Carboplatin is given as an IV-bolus, over 30-60 minutes, every 3 weeks, for a maximum of 6 cycles (with standard pre- or post-treatment therapies at the investigator's discretion).

Global Team Leader

The purpose of this study is to test a study drug called patritumab. Patritumab may work when combined with other medications that are approved in the UK for treating Squamous Cell Carcinoma of the Head and Neck (SCCHN), called cetuximab, cisplatin or carboplatin. It is hoped that patritumab may have some benefit in treating patients with cancer. This study will help identify how much patritumab can be given in combination with cetuximab, and cisplatin or carboplatin. This study will show how safe and how well tolerated patritumab is when these medications are given together.

The trial will be performed in two "phases" (Periods):

Period 1: Initial phase in which the recommended phase 2 dose (RP2D) is determined

Period 2: Extension phase in which participants who are deriving benefit (stable disease or better) will have the opportunity to continue treatment at the discretion of the Investigator

Patritumab With Cetuximab and a Platinum Containing Therapy for Patients With Head and Neck Cancer

An Open Label, Phase 1B Safety Evaluation of Patritumab (U31287) in Combination With Cetuximab Plus Platinum Containing Therapy In Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

DLTs are used to determine the maximum tolerated dose.

A titer is a way of expressing concentration. Titer testing employs serial dilution to obtain approximate quantitative information from an analytical procedure that inherently only evaluates as positive or negative. The titer corresponds to the highest dilution factor that still yields a positive reading.

Daiichi Sankyo

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Lung Diseases

Respiratory Tract Diseases

Thoracic Neoplasms

Respiratory Tract Neoplasms

Bronchial Neoplasms

Carcinoma, Bronchogenic

Amino Acids

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Placebo infusion every 3 weeks and oral erlotinib 150 mg/day

Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks) and oral erlotinib 150 mg/day

Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks)

Erlotinib

Placebo

Global Clinical Leader

1. Part A: Subjects will receive Patritumab or placebo with erlotinib. Progression-free survival will be the primary outcome. Subjects will need to have Epidermal Growth Factor Receptor (EGFR) wild-type, locally advance or metastatic NSCLC and have their cancer progressed after at least one prior systemic anti-cancer therapy, available recent or archival tumor specimen and may not have had previous EGFR-targeted regimen, anti-HER2 (Human Epidermal Growth Factor Receptor 2), anti-HER3, or anti-HER4 therapy. Subjects may have high heregulin or low heregulin.
2. Part B: Subjects will receive Patritumab or placebo with erlotinib. Overall survival will be the primary outcome. Subjects will need to have EGFR wild-type, locally advance or metastatic NSCLC and have their cancer progressed after at least one prior systemic anti-cancer therapy, available recent or archival tumor specimen and may not have had previous EGFR-targeted regimen, anti-HER2, anti-HER3, or anti-HER4 therapy. Only subjects with high heregulin will be enrolled.

Study of Patritumab in Combination With Erlotinib in Subjects With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC). (HER3-Lung)

Phase 3, Randomized, Placebo-Controlled, Double-Blind, Multi-Center, Two-Part Study of Patritumab (U3-1287) In Combination With Erlotinib in EGFR Wild-type Subjects With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) Who Have Progressed on at Least One Prior Systemic Therapy

PFS is defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression (as per RECIST Version 1.1 per investigator assessment) or death resulting from any cause.

Kaplan-Meier Estimate. Confidence interval (CI) for median was computed using the Brookmeyer-Crowley method. 80% confidence interval is included in the data table.

Percentage of participants still alive at the end of Part B

Key secondary efficacy endpoint: Percentage of participants who survived for the length of the trial

PFS is defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression (TTD, as per RECIST Version 1.1 per investigator assessment) or death resulting from any cause.

Key secondary efficacy endpoint: Objective response is defined as percentage of participants achieving complete response (CR) or partial response (PR)

Denominator for percentages is the number of subjects with measurable disease in the full analysis set. The best overall response is the best response \[in the order of CR, PR, stable disease (SD), and progressive disease (PD)\] among all overall responses recorded from the start of treatment until the subject withdraws from the study. If there is no post-baseline tumor assessment or all post-baseline tumor assessments with overall response being Inevaluable captured in the CRF, the best overall response is classified as Inevaluable.

Key secondary efficacy endpoint: Objective response is defined as percentage of participants achieving complete response or partial response

Denominator for percentages is the number of subjects with measurable disease in the full analysis set. The best overall response is the best response (in the order of CR, PR, SD, and PD) among all overall responses recorded from the start of treatment until the subject withdraws from the study. If there is no post-baseline tumor assessment or all post-baseline tumor assessments with overall response being Inevaluable captured in the CRF, the best overall response is classified as Inevaluable.

Parexel

Treatment emergent (TE) adverse events (AEs) are reported for patritumab only. If relatedness is missing, the AE is counted as related to patritumab.

Placebo + Erlotinib

Patritumab + Erlotinib

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Histology subtype

Histology subtype (for randomization)

Eastern Cooperative Oncology Group (ECOG) Score

Heregulin (HRG) expression from Interactive Web/Voice Response System (IXRS)

Part A: Progression Free Survival (PFS) in Heregulin-high Participants

Part A: Progression Free Survival (PFS) in Heregulin-low Participants

No participants were analyzed for Part B endpoints because the trial was terminated at the end of Part A.

Part B: Overall Survival

Part A: Overall Survival in HRG High Participants

Part A: Key Secondary Efficacy Endpoint: Overall Survival in HRG Low Participants

Part B: Key Secondary Efficacy Endpoint: PFS, TTD

Evaluable participants in the full analysis set

Part A: Objective Response Rate (ORR) in HRG High Participants

Part A: Objective Response Rate (ORR) in HRG Low Participants

Overall Study

All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin)

All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin)

Patritumab initial loading dose is 18 mg/kg IV over 60 minutes followed by a maintenance dose of 9 mg/kg IV over 60 minutes (± 10 minutes) every three weeks

Cetuximab 400 mg/mg/m\^2 IV loading dose, followed by 250 mg/m\^2 weekly

Cisplatin at 100 mg/m\^2 IV infused over 1 hour, every three weeks up to a maximum of 6 cycles

Carboplatin IV over 30 to 60 minutes, every 3 weeks for a maximum of 6 cycles

Kevin Harrington, Prof, MD

This study will test an investigational study drug called patritumab. It is a 'randomized study' which means participants have an equal chance of being assigned to receive the experimental medication (patritumab) or a substance that looks like the experimental product, but is not (placebo). Patritumab may work when combined with other medications that are approved for the treatment of head and neck cancer. They are called cetuximab, cisplatin or carboplatin. All participants will receive the other medications approved for treatment of head and neck cancer, even if they do not receive the experimental product.

Main objective of the trial:

The main objective of the trial is to evaluate progression-free survival (PFS) in the heregulin (HRG) high expression population from subjects treated with patritumab + cetuximab + platinum-based therapy compared to placebo + cetuximab + platinum-based therapy.

Patritumab With Cetuximab and a Platinum Agent for Squamous Cell Carcinoma (Cancer) of the Head and Neck (SCCHN )

Randomized, Placebo-controlled, Double-blind Phase 2 Study of Patritumab (U3-1287) in Combination With Cetuximab Plus Platinum-based Therapy in First Line Setting in Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at http://www.clinicalstudydatarequest.com. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://www.clinicalstudydatarequest.com/Study-Sponsors-DS-Details.aspx

PFS is defined as the time from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever comes first.

Median PFS is from Kaplan-Meier analysis. Confidence interval (CI) for median was computed using Brookmeyer-Crowley method.

Overall survival (OS) is defined as the time from the date of randomization to death due to any cause

Best overall response rate (ORR) is defined as the percentage of participants with Complete Response (CR) or Partial Response (PR)

18-64 Years

65-84 Years

Age, Customized

White

Asian

Other, Not Specified

Race/Ethnicity, Customized

Romania

Belgium

Hungary

Poland

United Kingdom

France

Germany

Region of Enrollment

0=Fully active

1=Restricted in Physically Strenuous Activity

2=Ambulatory and Capable of All Self-Care

Eastern Cooperative Oncology Group (ECOG) Performance Status

Heregulin-high population - Patritumab vs Placebo

Participants in the heregulin-high expression population

Progression Free Survival (PFS) in the Heregulin (HRG)-High Expression Population

The trial terminated before sufficient data were collected for this analysis (at approximately 12 months which is prior to the time point for this analysis).

Median Overall Survival

Percentage of Participants With Best Overall Response

Process 2 patritumab 18 mg/kg (loading dose) on Day 1 of Cycle 1 followed by Process 2 patritumab 9 mg/kg (maintenance dose) once every 21 days starting on Day 1 of Cycle 2 through Cycle 5.

patritumab

The purpose of this study is to assess the PK, safety, and tolerability of patritumab produced by a new manufacturing process (denoted as "Process 2 patritumab"). The data from this study will allow Process 2 patritumab to be compared to Process 1 patritumab to allow for any dose adjustments, if needed, and to bridge data from studies previously conducted with Process 1 patritumab to studies to be conducted with Process 2 patritumab. The hypothesis for this study is that the pharmacokinetics of Process 2 patritumab will be comparable to those of Process 1 patritumab.

Process 2 patritumab will be administered intravenously as a single, loading dose of 18 mg/kg over approximately 60 minutes at Cycle 1 Day 1 followed by 9 mg/kg administered every 21 days as a maintenance dose starting at Cycle 2 Day 1. This study will be conducted in 2 phases: a main study and an extension phase. The PK profile of Process 2 patritumab will be compared to historical data for Process 1 patritumab. Specifically, the PK parameters (AUC0-21d and Cmax as primary endpoints) for Process 2 patritumab 18 mg/kg (loading dose) will be compared to the PK parameters of Process 1 patritumab 18 mg/kg. Process 2 patritumab serum concentrations will be compared to Process 1 patritumab serum concentrations collected in the Phase 1 and Phase 2 studies by population PK methods and will be reported separately.

Study to Assess Pharmacokinetics, Immunogenicity and Safety/Tolerability of Patritumab (U3-1287)

Phase 1, Open-label Study Assessing the Pharmacokinetics, Immunogenicity and Safety/Tolerability of Process 2 Patritumab in Patients With Advanced, Refractory Solid Tumors

AUC (0-21 day) of patritumab obtained after a single infusion of Process 2 patritumab 18 mg/kg (loading dose)

Cmax of patritumab obtained after a single infusion of Process 2 patritumab 18 mg/kg (loading dose)

To assess the secondary PK parameters volume of distribution \[Vz\]

To assess the safety and tolerability of Process 2 patritumab (electrocardiograms \[ECG)

To characterize the formation of antibodies to patritumab human antihuman antibodies (HAHA) after infusion of Process 2 patritumab

To assess the secondary PK parameter concentration of patritumab at 504h \[C504\]

To assess the secondary PK parameters AUC to infinity \[AUC0-inf\]

To assess the secondary PK parameters time to Cmax (Tmax)

To assess the secondary PK parameters concentration at the end of infusion (Ceoi)

To assess the secondary PK parameters terminal elimination half-life (t 1/2)

To assess the secondary PK parameters clearance (CL)

To assess the secondary PK parameters trough concentration (Ctrough)

To assess the safety and tolerability of Process 2 patritumab echocardiograms/multi-gated acquisition \[MUGA\] scans

To assess the safety and tolerability of Process 2 patritumab adverse events \[AEs\] of Process 2 patritumab

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Patritumab With Cetuximab and a Platinum Containing Therapy for Patients With Head and Neck Cancer	NCT02350712	Squamous Cell C...	Patritumab Cetuximab Cisplatin Carboplatin	18 Years -	Daiichi Sankyo
Study of Patritumab in Combination With Erlotinib in Subjects With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC). (HER3-Lung)	NCT02134015	Lung Cancer Non-small Cell ...	Patritumab Erlotinib Placebo	20 Years -	Daiichi Sankyo
Patritumab With Cetuximab and a Platinum Agent for Squamous Cell Carcinoma (Cancer) of the Head and Neck (SCCHN )	NCT02633800	Head and Neck N...	Patritumab Cetuximab Cisplatin Carboplatin Placebo	18 Years -	Daiichi Sankyo
Study to Assess Pharmacokinetics, Immunogenicity and Safety/Tolerability of Patritumab (U3-1287)	NCT01957280	Solid Tumors	patritumab	18 Years -	Daiichi Sankyo

Spots Global Cancer Trial Database for patritumab

Every month we try and update this database with for patritumab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for patritumab

Every month we try and update this database with for patritumab cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for patritumab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.