Study of Patritumab in Combination With Erlotinib in Subjects With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC). (HER3-Lung) (HER3-Lung)
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| ClinicalTrials.gov Identifier: NCT02134015 |
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Recruitment Status :
Terminated
(Pre-defined criteria for continuation were not reached)
First Posted : May 8, 2014
Results First Posted : January 23, 2018
Last Update Posted : January 23, 2018
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- 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.
- 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Lung Cancer Non-small Cell Lung Cancer | Drug: Patritumab Drug: Erlotinib Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 145 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Study Start Date : | March 2014 |
| Actual Primary Completion Date : | November 11, 2016 |
| Actual Study Completion Date : | November 11, 2016 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Placebo + erlotinib
Placebo infusion every 3 weeks and oral erlotinib 150 mg/day
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Drug: Erlotinib
Oral erlotinib 150 mg/day Drug: Placebo Placebo infusion every 3 weeks
Other Name: Matching Placebo |
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Experimental: Patritumab + erlotinib
Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks) and oral erlotinib 150 mg/day
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Drug: Patritumab
Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks)
Other Name: U3-1287 Drug: Erlotinib Oral erlotinib 150 mg/day |
- Part A: Progression Free Survival (PFS) in Heregulin-high Participants [ Time Frame: by trial termination (at 20 months) ]
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.
- Part A: Progression Free Survival (PFS) in Heregulin-low Participants [ Time Frame: by trial termination (at 20 months) ]
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.
- Part B: Overall Survival [ Time Frame: 4 years ]Percentage of participants still alive at the end of Part B
- Part A: Overall Survival in HRG High Participants [ Time Frame: by trial termination (at 20 months) ]Key secondary efficacy endpoint: Percentage of participants who survived for the length of the trial
- Part A: Key Secondary Efficacy Endpoint: Overall Survival in HRG Low Participants [ Time Frame: by trial termination (at 20 months) ]Key secondary efficacy endpoint: Percentage of participants who survived for the length of the trial
- Part B: Key Secondary Efficacy Endpoint: PFS, TTD [ Time Frame: 4 years ]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.
- Part A: Objective Response Rate (ORR) in HRG High Participants [ Time Frame: by trial termination (at 20 months) ]
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.
- Part A: Objective Response Rate (ORR) in HRG Low Participants [ Time Frame: by trial termination (at 20 months) ]
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.
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| Ages Eligible for Study: | 20 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Must be greater or equal to 20 years of age
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Must have cytologically or histologically confirmed NSCLC with either:
- Metastatic disease (Stage IV) OR
- Stage IIIB disease not amenable to surgery or curative intent.
Note: It is permissible to use either AJCC Version 6.0 or the AJCC Version 7.0 staging system. For sites that use AJCC Version 7.0, T4M0 patients with other ipsilateral nodules and N0-N2 are still eligible.
- If tumor histology is adenocarcinoma, must have wild-type EGFR genotype as assessed by a validated assay that includes exon 19 deletion and exon 21 (L858R) substitution.
- Must have received one or two prior lines of systemic chemotherapy for advanced or metastatic disease, one of which must be a platinum-doublet therapy.
- Must have disease progression or recurrence documented by radiographic assessment following treatment after last chemotherapy or chemoradiation regimen (completed within the previous 12 months).
- Must have available recent (before treatment start) or archival tumor specimen.
- Must have measurable disease for Part A, measurable disease or non-measurable disease for Part B
- Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Must have adequate hematological function
- Must have adequate renal function
- Must have adequate hepatic function
- Agreement to use effective contraception while on treatment and for at least 6 months after end of treatment
- Must have provided informed consent for study participation.
Exclusion Criteria:
- Lung adenocarcinoma with an Anaplastic Lymphoma Kinase (ALK) gene rearrangement
- Left ventricular ejection fraction (LVEF) less than 45%
- Prior EGFR-targeted regimen, anti-HER2, anti-HER3, or anti-HER4 therapy
- History of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for greater or equal to 5 years
- History of corneal disease
- History of interstitial lung disease (ILD)
- Clinically active brain metastases
- Uncontrolled hypertension
- Clinically significant ECG changes
- Clinically significant (in the opinion of the Investigator) ascites or pleural effusion requiring chronic medical intervention
- Myocardial infarction within 1 year before enrollment, symptomatic congestive heart failure, unstable angina, or unstable cardiac arrhythmia requiring medication
- Treatment with anticancer therapy, antibody-based therapy, retinoid therapy, or hormonal therapy within 4 weeks before study drug treatment
- Therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment; or palliative radiation within 2 weeks before study drug treatment
- Participation in clinical drug trials within 4 weeks
- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
- History of hypersensitivity to any of the study drugs or to any excipients.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02134015
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| Study Director: | Global Clinical Leader | Daiichi Sankyo, Inc. |
| Responsible Party: | Daiichi Sankyo, Inc. |
| ClinicalTrials.gov Identifier: | NCT02134015 |
| Other Study ID Numbers: |
U31287-A-U301 2013-004371-12 ( EudraCT Number ) |
| First Posted: | May 8, 2014 Key Record Dates |
| Results First Posted: | January 23, 2018 |
| Last Update Posted: | January 23, 2018 |
| Last Verified: | December 2017 |
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Carcinoma Non-Small-Cell Lung Lung Neoplasms Bronchogenic Bronchial Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site |
Neoplasms Lung Diseases Respiratory Tract Diseases Erlotinib Therapeutic Uses Pharmacologic Actions Molecular Mechanisms of Pharmacological Action |
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Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases |
Carcinoma, Bronchogenic Bronchial Neoplasms Erlotinib Hydrochloride Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |