Carcinoma, Non-Small-Cell LungPhase 1/2NCT01233687
AMG 102 and Erlotinib for Advanced Non-Small Cell Lung Cancer
A Phase 1/2 study testing AMG 102 and erlotinib in people with Carcinoma, Non-Small-Cell Lung, run by Ahmad Tarhini at 1 site in United States.
Trial summary
This is a phase I/II study of erlotinib and AMG 102 in previously treated subjects with advanced NSCLC. Subjects will be enrolled with recurrent or progressive advanced stage NSCLC that has been treated with at least one and a maximum of two prior chemotherapy regimens. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- AMG 102 and erlotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2011to Nov 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with recurrent or progressive advanced stage Non-small cell lung cancer (NSCLC,no SCLC component) who have been treated with at least one and a maximum of two prior chemotherapy regimens for advanced NSCLC. Chemotherapy as part of initial potentially curative therapy (given as part of adjuvant or concomitant chemoradiotherapy) that was completed <1 year counts as 1 prior regimen. Prior erlotinib, other epidermal growth factor receptor (EGFR) TKIs or monoclonal antibodies targeting EGFR are not allowed.
- NOTE: Chemotherapy as part of initial potentially curative therapy (given as part of adjuvant or concomitant chemoradiotherapy) that was completed one or more years prior to screening for this study does not count as a prior regimen.
- If the tumor is refractory (progressed) after a prior chemotherapy regimen, then that regimen would count. If a prior chemotherapy regimen has been changed due to other reasons than disease progression (e.g. poor tolerance, allergic reaction), then it would not count as a separate prior regimen. A chemotherapy drug added for "maintenance" following disease stabilization or response to a chemotherapy regimen (in the absence of prior disease progression) does not count as a separate prior regimen.
- NOTE: Pathology reports documenting the diagnosis of NSCLC are required to be reviewed by the screening physician investigator.
- Measurable disease (RECIST version 1.1) (for phase II part only).
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 and life expectancy of ≥ 3 months.
Show all 16Show fewer
- NOTE: For the phase I part of the study, patients with ECOG Performance Status 2 will be excluded.
- Age ≥ 18 years old and ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed.
- Patients must meet the following laboratory criteria (within 14 days prior to study registration):
- oHematology: Absolute neutrophil count (ANC) ≥ 1500/mm³ Platelets ≥ 100,000/mm³ Hemoglobin ≥ 9 g/dL International normalized ratio (INR) ≤ 1.5 or prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits (WNL) of the institution oBiochemistry: Total Bilirubin within normal institutional limits. AST/SGOT and ALT/SGPT ≤ 2.5 x upper limit of normal (ULN), except if there is known hepatic metastasis, wherein transaminases may be ≤ 5 x institutional ULN.
- Creatinine clearance 45 ml/min or higher calculated using the Cockcroft-Gault formula. Multiply the number by 0.85 if the patient is female.
- Patients must have fully recovered from the effects of any prior surgery, chemotherapy or radiation therapy. In the case of residual effects, these must be clinically stable, grade 1 or less in severity and do not meet other protocol exclusion criteria. A minimum time period of 3 weeks should elapse between the completion of radiation therapy for recurrent/metastatic disease and enrollment in the study. A minimum of 4 weeks should elapse between the completion of chemotherapy or any experimental therapy and enrollment in the study. A minimum of 4 weeks should elapse between prior major surgery (such as open biopsy or significant traumatic injury) and enrollment in the study. A minimum of 2 weeks should elapse between prior minor surgical procedures (such as chemotherapy infusion port placement or core visceral organ biopsy) and enrollment in the study.
- If patient has history of brain metastases, brain lesions should have been treated with surgery and/or radiation and be stable on repeat imaging and patients should be neurologically stable on a stable or tapering dose of corticosteroids.
- No history of prior malignancy, with the exception of curatively treated squamous cell or basal carcinoma of the skin or in situ cervical cancer, unless there is a 3-year disease-free interval.
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days of the first administration of study treatment and must be willing to use two methods of contraception one of them being a barrier method or abstain from sexual activity during the study and for 6 months after last study drug administration. Sexually active males and their female partners must agree to use two methods of accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the study.
- All patients must have given signed, informed consent prior to registration on study.
Who cannot join
- Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required. This is due to the unknown effects of AMG102.
- Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent.
- Patients who have mixed tumors with small-cell elements are ineligible.
- Pregnancy or lactation. All females of child-bearing potential must have negative serum or urine pregnancy tests within 7 days prior to starting study treatment.
- Prior treatment of NSCLC with EGFR TKIs or monoclonal antibodies targeting EGFR.
- A serious active infection (>grade 2) within 7 days of enrollment.
Show all 12Show fewer
- A serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
- Untreated brain metastases.
- A major surgical procedure or significant traumatic injury within 28 days of beginning treatment, or anticipation of the need for major surgery during the course of the study per inclusion criterion 3.1. In addition, if a patient has not yet recovered from prior minor surgery (such as central venous access device or fine needle aspiration biopsy).
- Thrombosis or vascular ischemic events within the last twelve months, such as deep venous thrombosis, pulmonary embolism, transient ischemic attack, cerebral infarction, or myocardial infarction
- Concurrent or prior (within 7 days of enrollment) anticoagulation therapy, except for the use of low dose coumarin-type anticoagulants or low molecular weight heparin for prophylaxis against central venous catheter thrombosis
- Presence of peripheral edema > Grade 2 (CTCAE version 4).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232
About this study
Official title: A Phase I/II Trial of AMG 102 and Erlotinib in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer
This is a phase I/II study of erlotinib and AMG 102 in previously treated subjects with advanced NSCLC. Subjects will be enrolled with recurrent or progressive advanced stage NSCLC that has been treated with at least one and a maximum of two prior chemotherapy regimens. The Phase I part of the study will enroll 8-16 subjects with the Phase II part enrolling 21-45 subjects.
The Phase I part of the study is designed to determine how safest the combination of AMG 102 and erlotinib is and the recommended dose for the Phase II part. The Phase II part is to determine whether the combination of AMG102 and erlotinib works enough to warrant further interest in this combination.
Read the detailed description
While modest improvements have been made in survival and quality of life in patients with advanced NSCLC there is a need to explore new agents and combinations with novel mechanisms of action in an effort to improve clinical outcomes in this patient population. The HGF/c-MET pathway inhibition is a promising novel target in NSCLC. Preclinical evidence support the combined targeting of EGFR and HGF/c-MET pathways in NSCLC as a strategy that may result in enhanced antitumor activity. Inhibition of both HGF/c-Met and EGFR pathways can be accomplished by utilizing the combination of AMG 102 and erlotinib in patients with advanced NSCLC. Therefore, we propose a safety and efficacy, phase I/II clinical trial of the combination in patients with previously treated, advanced NSCLC.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- AMG 102 and erlotinib
- Keywords
- Recurrent, progressive, advanced
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 102 and erlotinibDrug
Also called Rilotumumab
Dose Level -2 Dose level -1 Dose Level 0 AMG 102 5 mg/kg 7.5 mg/kg 15 mg/kg Erlotinib 150 mg 150 mg 150 mg
The first cohort of patients in the phase I portion will start at dose level 0 of AMG102.
| Study group | Role | What they receive |
|---|---|---|
| AMG 102 and erlotinib | Experimental | Combination of AMG 102 and erlotinib Receives: Drug: AMG 102 and erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants That Experienced a Dose Limiting Toxicity
Determination of the safety and recommended phase II dose of AMG 102 when combined with erlotinib for the treatment of patients with advanced, previously-treated NSCLC.
Measured: During first cycle of treatment (3 weeks)
Disease Control Rate (DCR)
Using RECIST v1.1 criteria, DCR was determined by following equation: the number of complete response (CR) participants + the number of partial response (PR) participants + the number of stable disease (SD) participants / the number of complete response (CR) participants + the number of partial response (PR) participants + the number of stable disease (SD) participants + the number of progressive disease (PD) participants.
Measured: Six weeks from initiation of treatment with AMG 102 + Erlotinib
Secondary outcomes (3)
Objective Response Rate (ORR/Clinical Response)
Using RECIST v1.1 criteria, ORR was determined by following equation: the number of partial response (PR) participants / the number of partial response (PR) participants + the number of stable disease (SD) participants + the number of progressive disease (PD) participants.
Measured: Up to 6 months
Progression-free Survival (PFS)
Progression-free survival is defined as the time from the start of treatment until first evidence of disease progression, death, or date of last contact. The (median) length of time that subjects with previously-treated advanced NSCLC, who were treated with the combination of AMG 102 and erlotinib, are both alive and free of disease progression as estimated by the Kaplan-Meier method. For participants not known to have died as of the data cut-off date and who did not have PD, the PFS date was censored at the last contact date (contacts considered in the determination of last progression free disease assessment).
Measured: Up to 24 months (after the first patient is accrued)
Overall Survival (OS)
Overall Survival was computed for all participants and is defined as the time between start of treatment and death. The (median) length of time in months that subjects with previously-treated advanced NSCLC, treated with the combination of AMG 102 and erlotinib, remain alive estimated by the Kaplan-Meier method.
Measured: Up to 24 months (after the first evaluable patient is accrued)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2010 (estimated)
- Study startAug 2011
- Primary completionNov 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ahmad Tarhini
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor-investigator, Ahmad Tarhini, University of Pittsburgh
- Investigators
- Ahmad Tarhini, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01233687
- Sponsor's protocol ID
- 10-058
- Status last verified
- May 2017
- First submitted
- 2 Nov 2010
- Last updated
- 22 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of AMG 102 and Erlotinib in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT01233687
- Acronym / sponsor ID
- 10-058
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Keywords
- Recurrent, progressive, advanced
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Ahmad TarhiniUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- Aug 2011
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 3 Nov 2010 (estimated)
- Results
- Posted 1 Sep 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase I/II study of erlotinib and AMG 102 in previously treated subjects with advanced NSCLC. Subjects will be enrolled with recurrent or progressive advanced stage NSCLC that has been treated with at least one and a maximum of two prior chemotherapy regimens. The Phase I part of the study will enroll 8-16 subjects with the Phase II part enrolling 21-45 subjects.
The Phase I part of the study is designed to determine how safest the combination of AMG 102 and erlotinib is and the recommended dose for the Phase II part. The Phase II part is to determine whether the combination of AMG102 and erlotinib works enough to warrant further interest in this combination.
Detailed description
While modest improvements have been made in survival and quality of life in patients with advanced NSCLC there is a need to explore new agents and combinations with novel mechanisms of action in an effort to improve clinical outcomes in this patient population. The HGF/c-MET pathway inhibition is a promising novel target in NSCLC. Preclinical evidence support the combined targeting of EGFR and HGF/c-MET pathways in NSCLC as a strategy that may result in enhanced antitumor activity. Inhibition of both HGF/c-Met and EGFR pathways can be accomplished by utilizing the combination of AMG 102 and erlotinib in patients with advanced NSCLC. Therefore, we propose a safety and efficacy, phase I/II clinical trial of the combination in patients with previously treated, advanced NSCLC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AMG 102 and erlotinib | Experimental | Drug: AMG 102 and erlotinibCombination of AMG 102 and erlotinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients with recurrent or progressive advanced stage Non-small cell lung cancer (NSCLC,no SCLC component) who have been treated with at least one and a maximum of two prior chemotherapy regimens for advanced NSCLC. Chemotherapy as part of initial potentially curative therapy (given as part of adjuvant or concomitant chemoradiotherapy) that was completed <1 year counts as 1 prior regimen. Prior erlotinib, other epidermal growth factor receptor (EGFR) TKIs or monoclonal antibodies targeting EGFR are not allowed.
- NOTE: Chemotherapy as part of initial potentially curative therapy (given as part of adjuvant or concomitant chemoradiotherapy) that was completed one or more years prior to screening for this study does not count as a prior regimen.
- If the tumor is refractory (progressed) after a prior chemotherapy regimen, then that regimen would count. If a prior chemotherapy regimen has been changed due to other reasons than disease progression (e.g. poor tolerance, allergic reaction), then it would not count as a separate prior regimen. A chemotherapy drug added for "maintenance" following disease stabilization or response to a chemotherapy regimen (in the absence of prior disease progression) does not count as a separate prior regimen.
- NOTE: Pathology reports documenting the diagnosis of NSCLC are required to be reviewed by the screening physician investigator.
- Measurable disease (RECIST version 1.1) (for phase II part only).
Key exclusion criteria (12 listed)
- Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required. This is due to the unknown effects of AMG102.
- Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent.
- Patients who have mixed tumors with small-cell elements are ineligible.
- Pregnancy or lactation. All females of child-bearing potential must have negative serum or urine pregnancy tests within 7 days prior to starting study treatment.
- Prior treatment of NSCLC with EGFR TKIs or monoclonal antibodies targeting EGFR.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMG 102 and erlotinibAlso: RilotumumabDose Level -2 Dose level -1 Dose Level 0 AMG 102 5 mg/kg 7.5 mg/kg 15 mg/kg Erlotinib 150 mg 150 mg 150 mg The first cohort of patients in the phase I portion will start at dose level 0 of AMG102. | Drug | AMG 102 and erlotinib |
Primary outcome
Percentage of Participants That Experienced a Dose Limiting Toxicity
Time frame: During first cycle of treatment (3 weeks)
Determination of the safety and recommended phase II dose of AMG 102 when combined with erlotinib for the treatment of patients with advanced, previously-treated NSCLC.
Disease Control Rate (DCR)
Time frame: Six weeks from initiation of treatment with AMG 102 + Erlotinib
Using RECIST v1.1 criteria, DCR was determined by following equation: the number of complete response (CR) participants + the number of partial response (PR) participants + the number of stable disease (SD) participants / the number of complete response (CR) participants + the number of partial response (PR) participants + the number of stable disease (SD) participants + the number of progressive disease (PD) participants.
3 secondary outcomes
Objective Response Rate (ORR/Clinical Response)
Time frame: Up to 6 months
Progression-free Survival (PFS)
Time frame: Up to 24 months (after the first patient is accrued)
Overall Survival (OS)
Time frame: Up to 24 months (after the first evaluable patient is accrued)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Carcinoma, Non-Small-Cell Lung
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ahmad Tarhini, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AMG 102 and erlotinib in people with Carcinoma, Non-Small-Cell Lung, run by Ahmad Tarhini at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Sep 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants That Experienced a Dose Limiting Toxicity (time frame: During first cycle of treatment (3 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2017.