Recurrent Non-small Cell Lung CancerPhase 1NCT01911507
INC280 and Erlotinib Hydrochloride in Treating Patients With Non-small Cell Lung Cancer
A Phase 1 study testing INC280 and erlotinib hydrochloride in people with Recurrent Non-small Cell Lung Cancer, run by University of California, Davis at 2 sites in United States.
Trial summary
This phase I trial studies the side effects and best dose of c-Met inhibitor INCB028060 and erlotinib hydrochloride when given together in treating patients with previously treated non-small cell lung cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Non-small Cell Lung Cancer
- What is being tested?
- INC280 and erlotinib hydrochloride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 2 sitesUnited States
- Study dates
- 27 Aug 2013to 26 Aug 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 must provide written informed consent prior to any screening procedures
- Willing and able to comply with scheduled visits, treatment plan and laboratory tests
- Patient is able to swallow and retain oral medication
- Histologically or cytologically documented diagnosis of NSCLC
- Must have evidence of MET expression by fluorescence in situ hybridization (FISH), MET immunohistochemistry (IHC) score of 2-3+, reverse-transcriptase polymerase chain reaction (RT-PCR) or a mutation
- Tumor tissue for correlative studies is mandatory
Show all 24Show fewer
- Patients in expansion cohort A will have a biopsy (which is standard of care) at the time of progression that shows evidence of MET positivity and meets the criteria for acquired resistance per the Jackman criteria
- Previously received treatment with a single-agent erlotinib
- A tumor that harbors an EGFR mutation known to be associated with drug sensitivity (i.e. G719X, exon 19 deletion, L858R, L861Q)
- Systemic progression of disease (Response Evaluation Criteria in Solid Tumors [RECIST] or World Health Organization [WHO]) while on continuous treatment with gefitinib or erlotinib
- Patients must have measurable disease; disease in previously irradiated sites is considered measurable if there is clear disease progression following radiation therapy
- Failed 1-2 prior chemotherapies for advanced disease; prior erlotinib is allowed in the dose finding phase and expansion cohort A (Patients in expansion cohort B must be erlotinib naïve and have v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog [KRAS] wild type tumor)
- Patients must be willing to be off therapy for a minimum of two weeks (In expansion cohort A patients on erlotinib do not have to discontinue treatment)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Life expectancy greater than 3 months
- Hemoglobin > 9 g/dL (International System [SI] units: 90 g/L) without transfusion support or growth factors within 10 days of starting INC280
- Platelet count >= 75 x 10^9/L
- Absolute neutrophil count (ANC) >= 1.2 x 10^9/L without growth factor support
- Total bilirubin =< 2 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 2.5 x upper limit of normal (ULN)
- Serum creatinine =< 2 x ULN
- Serum amylase =< ULN
- Serum lipase =< ULN
- Fasting serum triglyceride level =< 500 mg/dL
Who cannot join
- Patients who have had major surgery within 4 weeks of initiation of study medication, excluding the placement of vascular access
- Patients with concurrent uncontrolled medical conditions that may interfere with their participation in the study or potentially affect the interpretation of the study data
- Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia
- Severely impaired lung function
- Active (acute or chronic) or uncontrolled infection
- Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
Show all 27Show fewer
- Liver disease (i.e. cirrhosis, chronic active hepatitis, chronic persistent hepatitis)
- Symptomatic central nervous system (CNS) metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease
- Note: Patients with controlled CNS metastases are allowed; radiotherapy or surgery for CNS metastases must have been completed > 2 weeks prior to study entry; patients must be neurologically stable, having no new neurologic deficits on clinical examination, and no new findings on CNS imaging; steroid use for management of CNS metastases must be at a stable dose for two weeks preceding study entry
- Receiving drugs known to be strong inducers of cytochrome P450 3A4 (CYP3A4) or inhibiting drugs known to interact with erlotinib including, but not limited to: enzyme-inducing anticonvulsants, rifampicin, rifabutin, St John wort and ketoconazole
- Treatment with proton pump inhibitors within 3 days prior to study entry
- Currently receiving any prohibited medications including vitamins and herbal supplements
- Any other condition that would, in the investigator's judgment, contraindicate participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL)
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months after stopping study drug; highly effective contraception methods include:
- Total abstinence or
- Male or female sterilization or
- Combination of any two of the following (a+b or a+c or b+c):
- (a) Use of oral, injected or implanted hormonal methods of contraception
- (b) Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- (c) Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
- Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
- Sexually active males must use a condom during intercourse while taking the drug and for 3 months after stopping study drug and should not father a child in this period; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
- Patients unwilling or unable to comply with the protocol
- Prior treatment with a MET inhibitor or hepatocyte growth factor (HGF) targeting agent
- No history of another active cancer
- Human immunodeficiency virus (HIV) seropositivity
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of California, Davis
Sacramento, California, 95817
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
About this study
Official title: Phase I Study of INC280 Plus Erlotinib in Patients With C-Met Expressing Non-Small Cell Lung Cancer
This phase I trial studies the side effects and best dose of c-Met inhibitor INCB028060 and erlotinib hydrochloride when given together in treating patients with previously treated non-small cell lung cancer. C-Met inhibitor INCB028060 and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose of INC280 (c-Met inhibitor INCB028060) plus erlotinib (erlotinib hydrochloride) in patients with met proto-oncogene (MET) expressing non-small cell lung cancer (NSCLC).
SECONDARY OBJECTIVES:
- To describe the toxicity profile of INC280 plus erlotinib. II. To determine the preliminary efficacy of INC280 plus erlotinib. III. To characterize the pharmacokinetic behavior of this combination.
TERTIARY OBJECTIVES:
- To collect blood and tumor samples for exploratory analysis of the MET and epidermal growth factor receptor (EGFR) signaling pathways.
OUTLINE: This is a dose-escalation study.
Patients receive c-Met inhibitor INCB028060 orally (PO) twice daily (BID) and erlotinib hydrochloride PO once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
- Conditions
- Recurrent Non-small Cell Lung Cancer
- Being tested
- INC280, erlotinib hydrochloride
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INC280Drug
Also called INCB028060
Given PO
erlotinib hydrochlorideDrug
Also called CP-358,774, erlotinib, OSI-774
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment ( INCB028, erlotinib) | Experimental | Patients receive INC280 PO BID and erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: INC280; Drug: erlotinib hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of c-Met inhibitor INCB028060 and erlotinib, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V4
The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize toxicities and side effects by dose and by course. Baseline information (e.g. the extent of prior therapy) and demographic information will be presented.
Measured: Up to 28 days after a full course of therapy
Secondary outcomes (6)
Toxicities as measured by NCI CTCAE V4
The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course. Baseline information (e.g. the extent of prior therapy) and demographic information will be presented.
Measured: Up to 30 days
Overall response rate among patients with measurable disease, measured by RECIST 1.1
Response rate among patients with measurable disease will be summarized by exact binomial confidence intervals.
Measured: Up to 30 days
Disease control rate, measured by RECIST 1.1
Measured: Up to 30 days
Progression-free survival
Summarized with Kaplan-Meier plots. Median time to progression will be estimated using standard life table methods.
Measured: Duration of time from start of treatment to time of progression or death, assessed up to 30 days
Overall survival
Summarized with Kaplan-Meier plots. Median time to progression will be estimated using standard life table methods.
Measured: Duration of time from the start of treatment to death from any cause, assessed up to 30 days
Concentrations of c-Met inhibitor INCB028060 in plasma, measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay
Measured: Days 15-16 of course 1, days 1 and 15 of course 2, and day 1 of courses 3-4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2013 (estimated)
- Study start27 Aug 2013
- Primary completion26 Aug 2020
- Study completion26 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals, National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Karen Kelly, University of California, Davis
- Investigators
- Karen Kelly, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01911507
- Sponsor's protocol ID
- 435021
- Other IDs
- UCDCC#238, P30CA093373, CINC280XUS02T
- Status last verified
- Sep 2021
- First submitted
- 23 Jul 2013
- Last updated
- 13 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of INC280 Plus Erlotinib in Patients With C-Met Expressing Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT01911507
- Acronym / sponsor ID
- 435021
- Conditions
- Recurrent Non-small Cell Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals, National Cancer Institute (NCI)
- Study start
- 27 Aug 2013 (actual)
- Primary completion
- 26 Aug 2020 (actual)
- Study completion
- 26 Aug 2020 (actual)
- First posted
- 30 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies the side effects and best dose of c-Met inhibitor INCB028060 and erlotinib hydrochloride when given together in treating patients with previously treated non-small cell lung cancer. C-Met inhibitor INCB028060 and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose of INC280 (c-Met inhibitor INCB028060) plus erlotinib (erlotinib hydrochloride) in patients with met proto-oncogene (MET) expressing non-small cell lung cancer (NSCLC).
SECONDARY OBJECTIVES:
- To describe the toxicity profile of INC280 plus erlotinib. II. To determine the preliminary efficacy of INC280 plus erlotinib. III. To characterize the pharmacokinetic behavior of this combination.
TERTIARY OBJECTIVES:
- To collect blood and tumor samples for exploratory analysis of the MET and epidermal growth factor receptor (EGFR) signaling pathways.
OUTLINE: This is a dose-escalation study.
Patients receive c-Met inhibitor INCB028060 orally (PO) twice daily (BID) and erlotinib hydrochloride PO once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment ( INCB028, erlotinib) | Experimental | Drug: INC280, Drug: erlotinib hydrochloridePatients receive INC280 PO BID and erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Patients must provide written informed consent prior to any screening procedures
- Willing and able to comply with scheduled visits, treatment plan and laboratory tests
- Patient is able to swallow and retain oral medication
- Histologically or cytologically documented diagnosis of NSCLC
- Must have evidence of MET expression by fluorescence in situ hybridization (FISH), MET immunohistochemistry (IHC) score of 2-3+, reverse-transcriptase polymerase chain reaction (RT-PCR) or a mutation
Key exclusion criteria (27 listed)
- Patients who have had major surgery within 4 weeks of initiation of study medication, excluding the placement of vascular access
- Patients with concurrent uncontrolled medical conditions that may interfere with their participation in the study or potentially affect the interpretation of the study data
- Symptomatic central nervous system (CNS) metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease
- Receiving drugs known to be strong inducers of cytochrome P450 3A4 (CYP3A4) or inhibiting drugs known to interact with erlotinib including, but not limited to: enzyme-inducing anticonvulsants, rifampicin, rifabutin, St John wort and ketoconazole
- Treatment with proton pump inhibitors within 3 days prior to study entry
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 |
|---|---|---|
| INC280Also: INCB028060Given PO | Drug | Treatment ( INCB028, erlotinib) |
| erlotinib hydrochlorideAlso: CP-358,774, erlotinib, OSI-774Given PO | Drug | Treatment ( INCB028, erlotinib) |
Primary outcome
Maximum tolerated dose (MTD) of c-Met inhibitor INCB028060 and erlotinib, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V4
Time frame: Up to 28 days after a full course of therapy
The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize toxicities and side effects by dose and by course. Baseline information (e.g. the extent of prior therapy) and demographic information will be presented.
6 secondary outcomes
Toxicities as measured by NCI CTCAE V4
Time frame: Up to 30 days
Overall response rate among patients with measurable disease, measured by RECIST 1.1
Time frame: Up to 30 days
Disease control rate, measured by RECIST 1.1
Time frame: Up to 30 days
Progression-free survival
Time frame: Duration of time from start of treatment to time of progression or death, assessed up to 30 days
Overall survival
Time frame: Duration of time from the start of treatment to death from any cause, assessed up to 30 days
Concentrations of c-Met inhibitor INCB028060 in plasma, measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay
Time frame: Days 15-16 of course 1, days 1 and 15 of course 2, and day 1 of courses 3-4
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2021.
Related trials for Recurrent 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
RecruitingObservational study
Patient-Specific MRD Liquid Biopsy in Resected NSCLC: Plasma and Bronchial Washing ctDNA
Non-Small Cell Lung Cancer, Minimal Residual Disease
RecruitingPhase 3
Testing the Impact of an Anti-Cancer Drug, Atezolizumab, After Surgery to Prevent Early Stage Non-small Cell Lung Cancer From Returning, AASI-NSCLC Trial
Lung Non-Small Cell Carcinoma
RecruitingPhase 3
Osimertinib With or Without Bevacizumab as Initial Treatment for Patients With EGFR-Mutant Lung Cancer
Advanced Lung Non-Squamous Non-Small Cell Carcinoma, Metastatic Lung Non-Squamous Non-Small Cell Carcinoma
RecruitingPhase 1
A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors
Metastatic Solid Tumor, Recurrent Solid Tumor
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.
Karen Kelly principal investigator
University of California, Davis
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing INC280 and erlotinib hydrochloride in people with Recurrent Non-small Cell Lung Cancer, run by University of California, Davis at 2 sites 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 24 inclusion and 27 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 13 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum tolerated dose (MTD) of c-Met inhibitor INCB028060 and erlotinib, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V4 (time frame: Up to 28 days after a full course of therapy). 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 13 Oct 2021.