Lung CancerPhase 1NCT01999985
Phase I Trial of Afatinib (BIBW 2992) and Dasatinib in Non-small Cell Lung Cancer (NSCLC)
A Phase 1 study testing Dasatinib - 1A, Afatinib - 1A and Dasatinib - 1B in people with Lung Cancer and Non-small Cell Lung Cancer (NSCLC), run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The purpose of this study is to: Find out if the study drugs Afatinib and Dasatinib can be safely given together to patients with lung cancer Learn how these two drugs work in cancer cells when they are combined Learn more about the side effects of these two drugs when combined Find the highest doses of the study… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer, Non-small Cell Lung Cancer (NSCLC)
- What is being tested?
- Dasatinib - 1A, Afatinib - 1A and Dasatinib - 1B
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Dec 2013to 30 May 2019
- Phase
- Phase 1
- 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
- Pathologically or cytologically documented Stage IIIB/IV non-small cell lung cancer, or unresectable recurrent disease following locoregional treatment.
- For Phase 1B Extension Only:
- Either or both of the following: A tumor which harbors an activating Epidermal Growth Factor Receptor (EGFR) - mutation; History of objective response, or stable disease for at least 6 months, after treatment with erlotinib, afatinib, or gefitinib.
- Either or both of the following: Progression or recurrence of disease after receiving prior continuous gefitinib, afatinib, or erlotinib; A tumor known to harbor a de novo T790M mutation, which is known to confer EGFR TKI resistance.
- Participants are allowed to have received systemic chemotherapy or investigational therapy in the intervening period prior to trial enrollment
- Capable of giving written informed consent.
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- Evaluable disease, as follows: For Phase 1A Dose Escalation: Have the presence of any evaluable disease, including bone metastases, effusion, or cystic metastases. For Phase 1B Extension Only: Have progressive and measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST v 1.1).
- Reproductive potential must be either terminated (by surgery, radiation, or menopause) or attenuated by the use of an approved contraceptive method during and for 3 to 6 months following the study.
- Participant agrees that IV bisphosphonates will be withheld during the first 8 weeks of dasatinib therapy due to risk of hypocalcemia.
- Have recovered from prior drug-related toxicity to Grade ≤ 1 Common Terminology Criteria for Adverse Events (CTCAE) v4, within 21 days of initiation of on-study treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at initial enrollment, as assessed by clinician or investigator.
Who cannot join
- Have previously completed or withdrawn from this study or any other study investigating dasatinib. Prior treatment with other tyrosine kinases, including afatinib, is acceptable.
- Prior recent systemic or investigational therapy within 21 days of initiation of study treatment. An exception is that epidermal growth factor receptor (EGFR) inhibitor may be continued up until 3 days of initiation of study treatment.
- Women who are pregnant or breastfeeding. Women of childbearing potential must have a negative pregnancy test (β-HCG test in urine or serum) prior to commencing study treatment.
- Patients with documented central nervous system or leptomeningeal metastasis (brain metastasis) at the time of study entry. Patients with prior brain metastasis may be considered if they have completed their treatment for brain metastasis and no longer require corticosteroids.
- Patients with disease progression in the central nervous system (CNS) only.
- Serious concomitant disorder, including active bacterial, fungal, or viral infection, incompatible with the study (at the discretion of the principal investigator).
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- Uncorrected severe electrolyte disorder, including severe potassium (<3.0 mEq/L) or magnesium ( < 1.0 mEq/L) deficiency.
- Any gastrointestinal disorder with diarrhea as a major symptom, such as Crohn's, or pre-existing chronic diarrhea Common Toxicity Criteria (CTC) Grade ≥ 2 of any etiology. Included are malabsorption disorders that in the opinion of the study physician may affect absorption of either afatinib or dasatinib.
- Prior major surgery or radiation therapy within 14 days of initiation of treatment.
- Electrocardiogram (ECG) abnormalities indicative of arrhythmia (at the discretion of the investigator).
- History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to enrollment.
- Baseline (< 1 month before treatment) cardiac left ventricular function with resting ejection fraction of less than 50% measured by multigated blood pool imaging of the heart (MUGA scan) or echocardiogram.
- Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, congenital long QT syndrome, or Torsades de pointes).
- Prolonged QTc interval on pre-entry electrocardiogram (> 470 msec for men and >480 msec for women per American College of Cardiology/American Heart Association [AHA/ACC] 2011 scientific statement).
- History of significant bleeding disorder unrelated to cancer, including diagnosed congenital bleeding disorders (e.g., von Willebrand's disease).
- Patients currently taking drugs that are generally accepted to have a high risk of causing Torsades de Pointes.
- Patients with pre-existing interstitial lung disease (ILD), or pericardial / pleural effusion of grade 2 or higher. Trace pericardial or pleural effusion is acceptable.
- Patients who require chronic oxygen therapy for chronic obstructive pulmonary disease or pleural effusions (malignant or benign).
- Patients requiring comedication with potent P-gp inhibitors (including cyclosporin, azithromycin, erythromycin, ketoconazole, itraconazole, quinidine, phenobarbital salt with quinidine, ritonavir, valspodar, verapamil) or inducers (including rifampicin).
- Known active hepatitis B infection, known active hepatitis C infection, or known HIV carrier.
- Known or suspected active drug or alcohol abuse.
- Known hypersensitivity to afatinib, dasatinib, or the excipients of any of the trial drugs.
- Laboratory exclusion criteria: Absolute neutrophil count (ANC) < 1000 / mm^3, Platelet count < 100,000 / mm^3, Serum creatinine ≥1.5 times the upper normal limit or calculated/measured creatinine Clearance ≤60 mL/min., Total bilirubin ≥1.5 mg/dL (>26 mol/L, SI unit equivalent), Aspartate amino transferase (AST) or Alanine amino transferase (ALT) ≥ 2.5 times the upper limit of normal (if related to liver metastases ≥ five times the upper limit of normal).
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: Phase I Trial Evaluating Safety and Tolerability of the Irreversible Epidermal Growth Factor Receptor Inhibitor Afatinib (BIBW 2992) in Combination With the SRC Kinase Inhibitor Dasatinib for Patients With Non-small Cell Lung Cancer (NSCLC)
The purpose of this study is to:
- Find out if the study drugs Afatinib and Dasatinib can be safely given together to patients with lung cancer
- Learn how these two drugs work in cancer cells when they are combined
- Learn more about the side effects of these two drugs when combined
- Find the highest doses of the study drugs Afatinib and Dasatinib that can be given safely without causing serious side effects
- Conditions
- Lung Cancer, Non-small Cell Lung Cancer (NSCLC)
- Being tested
- Dasatinib - 1A, Afatinib - 1A, Dasatinib - 1B, Afatinib - 1B
- Keywords
- Epidermal Growth Factor Receptor (EGFR), Tyrosine kinase inhibitors, Neoplasms, Lung Diseases, Respiratory Tract Diseases, Pleural Diseases, Pleural Neoplasms, Lung Neoplasms, Pleural Effusion, Pleural Effusion, Malignant, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, EGFR mutation, Afatinib, Dasatinib, Carcinoma, Bronchogenic, Gene Mutation, T790M mutation., Non-small cell lung cancer
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Neoplasms, Lung Diseases, Respiratory Tract Diseases, Pleural Diseases, Pleural Neoplasms, Pleural Effusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dasatinib - 1ADrug
Also called SPRYCEL®, BMS-354825, tyrosine kinase inhibitor, SRC Kinase Inhibitor
1A: Begins Day 8. Level 1 - 100 mg, Level 2 - 100 mg, Level 3 - 140 mg.
Afatinib - 1ADrug
Also called BIBW 2992, EGFR Inhibitor
1A: Begins Day 1. Level 1 - 30 mg, Level 2 - 40 mg, Level 3 - 40 mg.
Dasatinib - 1BDrug
In Phase 1B, a mutationally selected 20 participants (total) will be treated at the recommended dose to confirm tolerability and evaluate for early response signal.
Afatinib - 1BDrug
In Phase 1B, a mutationally selected 20 participants (total) will be treated at the recommended dose to confirm tolerability and evaluate for early response signal.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation and Dose Expansion | Experimental | Dose escalation followed by dose expansion. Escalation cohort: Afatinib and Dasatinib. This study is divided into two parts. The first 8 - 18 people will be entered in the first part, called Phase 1A. Then this part will end.
Expansion cohort:: Afatinib and Dasatinib. The next 20 people will enter into the second part, called Phase 1B. Receives: Drug: Dasatinib - 1A; Drug: Afatinib - 1A; Drug: Dasatinib - 1B; Drug: Afatinib - 1B |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Afatinib (BIBW 2992) in Combination With Dasatinib
The MTD for this combined treatment will be defined as either:
- The highest dosage cohort in which six patients had been treated and there were less than two dose limiting toxicities (DLTs) or,
- Afatinib at the highest tolerated dose investigated (40 mg by mouth [PO] daily) plus dasatinib at the highest tolerated dose investigated (cohort 3, 140 mg PO daily).
Measured: Up to 6 Months
Secondary outcomes (2)
Number of Participants With Objective Response
Estimates objective response rate (complete response [CR] and partial response [PR]) in participants with acquired EGFR resistance
Measured: Up to 6 Months
Median Progression Free Survival
Estimate the 6-month progression free survival (PFS) rate in participants with acquired EGFR resistance. Response Criteria for Phase 1B will follow RECIST v.1.1: Progressive Disease (PD) is defined as at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Measured: Up to 6 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2013 (estimated)
- Study start31 Dec 2013
- Primary completion21 Mar 2017
- Study completion30 May 2019
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 Lung CancerStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim, Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Ben Creelan, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01999985
- Sponsor's protocol ID
- MCC-17176
- Other IDs
- BI 1200.166, BMS CA180-379
- Status last verified
- Nov 2020
- First submitted
- 26 Nov 2013
- Last updated
- 27 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial Evaluating Safety and Tolerability of the Irreversible Epidermal Growth Factor Receptor Inhibitor Afatinib (BIBW 2992) in Combination With the SRC Kinase Inhibitor Dasatinib for Patients With Non-small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT01999985
- Acronym / sponsor ID
- MCC-17176
- Conditions
- Lung Cancer, Non-small Cell Lung Cancer (NSCLC)
- Keywords
- Epidermal Growth Factor Receptor (EGFR), Tyrosine kinase inhibitors, Neoplasms, Lung Diseases, Respiratory Tract Diseases, Pleural Diseases, Pleural Neoplasms, Lung Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim, Bristol-Myers Squibb
- Study start
- 31 Dec 2013 (actual)
- Primary completion
- 21 Mar 2017 (actual)
- Study completion
- 30 May 2019 (actual)
- First posted
- 3 Dec 2013 (estimated)
- Results
- Posted 14 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to:
- Find out if the study drugs Afatinib and Dasatinib can be safely given together to patients with lung cancer
- Learn how these two drugs work in cancer cells when they are combined
- Learn more about the side effects of these two drugs when combined
- Find the highest doses of the study drugs Afatinib and Dasatinib that can be given safely without causing serious side effects
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation and Dose Expansion | Experimental | Drug: Dasatinib - 1A, Drug: Afatinib - 1A, Drug: Dasatinib - 1B, Drug: Afatinib - 1BDose escalation followed by dose expansion. Escalation cohort: Afatinib and Dasatinib. This study is divided into two parts. The first 8 - 18 people will be entered in the first part, called Phase 1A. Then this part will end. Expansion cohort:: Afatinib and Dasatinib. The next 20 people will enter into the second part, called Phase 1B. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Pathologically or cytologically documented Stage IIIB/IV non-small cell lung cancer, or unresectable recurrent disease following locoregional treatment.
- For Phase 1B Extension Only:
- Capable of giving written informed consent.
- Evaluable disease, as follows: For Phase 1A Dose Escalation: Have the presence of any evaluable disease, including bone metastases, effusion, or cystic metastases. For Phase 1B Extension Only: Have progressive and measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST v 1.1).
- Reproductive potential must be either terminated (by surgery, radiation, or menopause) or attenuated by the use of an approved contraceptive method during and for 3 to 6 months following the study.
Key exclusion criteria (23 listed)
- Have previously completed or withdrawn from this study or any other study investigating dasatinib. Prior treatment with other tyrosine kinases, including afatinib, is acceptable.
- Prior recent systemic or investigational therapy within 21 days of initiation of study treatment. An exception is that epidermal growth factor receptor (EGFR) inhibitor may be continued up until 3 days of initiation of study treatment.
- Women who are pregnant or breastfeeding. Women of childbearing potential must have a negative pregnancy test (β-HCG test in urine or serum) prior to commencing study treatment.
- Patients with documented central nervous system or leptomeningeal metastasis (brain metastasis) at the time of study entry. Patients with prior brain metastasis may be considered if they have completed their treatment for brain metastasis and no longer require corticosteroids.
- Patients with disease progression in the central nervous system (CNS) only.
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 |
|---|---|---|
| Dasatinib - 1AAlso: SPRYCEL®, BMS-354825, tyrosine kinase inhibitor, SRC Kinase Inhibitor1A: Begins Day 8. Level 1 - 100 mg, Level 2 - 100 mg, Level 3 - 140 mg. | Drug | Dose Escalation and Dose Expansion |
| Afatinib - 1AAlso: BIBW 2992, EGFR Inhibitor1A: Begins Day 1. Level 1 - 30 mg, Level 2 - 40 mg, Level 3 - 40 mg. | Drug | Dose Escalation and Dose Expansion |
| Dasatinib - 1BIn Phase 1B, a mutationally selected 20 participants (total) will be treated at the recommended dose to confirm tolerability and evaluate for early response signal. | Drug | Dose Escalation and Dose Expansion |
| Afatinib - 1BIn Phase 1B, a mutationally selected 20 participants (total) will be treated at the recommended dose to confirm tolerability and evaluate for early response signal. | Drug | Dose Escalation and Dose Expansion |
Primary outcome
Maximum Tolerated Dose (MTD) of Afatinib (BIBW 2992) in Combination With Dasatinib
Time frame: Up to 6 Months
The MTD for this combined treatment will be defined as either: 1. The highest dosage cohort in which six patients had been treated and there were less than two dose limiting toxicities (DLTs) or, 2. Afatinib at the highest tolerated dose investigated (40 mg by mouth [PO] daily) plus dasatinib at the highest tolerated dose investigated (cohort 3, 140 mg PO daily).
2 secondary outcomes
Number of Participants With Objective Response
Time frame: Up to 6 Months
Median Progression Free Survival
Time frame: Up to 6 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- DOI: 10.1158/1538-7445.AM2016-CT060 Published 15 July 2016Link provided by the sponsor.
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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.
Ben Creelan, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dasatinib - 1A, Afatinib - 1A and Dasatinib - 1B in people with Lung Cancer and Non-small Cell Lung Cancer (NSCLC), run by H. Lee Moffitt Cancer Center and Research Institute 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 11 inclusion and 23 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 27 Nov 2020. 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 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?
Yes. Results are posted in the registry (first posted 14 Jun 2019). 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?
Maximum Tolerated Dose (MTD) of Afatinib (BIBW 2992) in Combination With Dasatinib (time frame: Up to 6 Months). 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 27 Nov 2020.