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Lung CancerPhase 1/2NCT00826449

Dasatinib and Erlotinib in Non-Small Cell Lung Cancer (NSCLC)

A Phase 1/2 study testing Dasatinib and Erlotinib in people with Lung Cancer and Non-Small Cell Lung Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The goal of the Phase I portion of this study is to find the highest tolerable dose of the combination of dasatinib and erlotinib hydrochloride that can be given to patients with advanced solid tumors. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Lung Cancer, Non-Small Cell Lung Cancer
What is being tested?
Dasatinib and Erlotinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
1 siteUnited States
Study dates
Feb 2009to Jun 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 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Advanced malignancy that is appropriate for systemic therapy without curative intent.
  • Patients must provide verbal and written informed consent indicating they are aware of the investigational nature of the study. Parental consent and patient assent is required for those aged 16-17.
  • Patients must be at least 16 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  • Adequate hematologic, hepatic, and renal function as follows: creatinine < 1.5 x the institutional upper limit of normal (ULN), total bilirubin < 2.0 x ULN, AST and ALT < 2.5 x ULN, absolute granulocytes >/= 1500/mm^3; platelets >/= 75,000 mm^3; hemoglobin >/= 10 g/dL.
  • Serum potassium, magnesium, and phosphate within the institutional limits of normal. Patients with low potassium, phosphate, or magnesium levels may be repleted to allow for protocol entry.
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  • Serum calcium >/= the institutional limits of normal. Patients with low calcium levels may be repleted to allow for protocol entry.
  • Ability to take oral medication (dasatinib and erlotinib must be swallowed whole)
  • Patients-both males \& females-w/reproductive potential must agree to use an adequate method of contraception to include hormonal contraceptives (birth control pills, injections, implants), intrauterine device (IUD), barrier contraceptive with spermicide, and/or abstinence throughout the study \& for at least 4 wks after the study drugs are stopped. Females w/ reproductive or childbearing potential include any female who has experienced menarche \& who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal
  • -Continued from Inclusion #9 - [defined as amenorrhea >/=12 consecutive mths;or women on hormone replacement therapy (HRT) w/ documented serum follicle stimulating hormone (FSH) level > 35 milli-International unit (mIU)/mL]. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
  • Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 72 hours prior to the start of study drug administration.
  • Asymptomatic brain metastases with prior cranial irradiation or resection are acceptable if there is no bleeding, no midline shift, and no need for steroids or anti-convulsants. Asymptomatic brain metastasis without prior treatment are acceptable if the largest lesion is less than 7 mm in diameter, there is no bleeding, midline shift, nor need for steroids or anti-convulsants.
  • Patient agrees to discontinue St. Johns Wort at least 5 days before starting dasatinib or erlotinib.
  • Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia.
  • The patient's O^2 saturation must be >92% on room air.
  • (Phase II only) - Patient has never received prior therapy with dasatinib, or erlotinib, or another epidermal growth factor receptor (EGFR) or Src family kinase (SFK) inhibitor.
  • (Phase I only) - Histological or unequivocal cytological proof of solid tumor malignancy.
  • (Phase I only) - At least one prior systemic chemotherapy or biological therapy for recurrent or metastatic solid tumor (i.e., this protocol therapy must be administered as second line or greater), ), except if there is no standard or experimental systemic therapy available. If no effective systemic agent is available for first line therapy, then patients may be enrolled on the phase I as first line therapy.
  • (Phase I only) - Prior radiotherapy is permitted (see exclusion criterion 4 for details on unallowable radiotherapy).
  • (Phase II only) - Histological or unequivocal cytological proof of NSCLC.
  • (Phase II only) - NSCLC that is appropriate for systemic therapy without curative intent: Stage IV, Stage IIIB with pleural effusion, or incurable recurrent disease after surgery or radiotherapy.
  • (Phase II only) - Zero to one line of prior systemic therapy for recurrent or metastatic NSCLC. Prior adjuvant chemotherapy or adjuvant biologic therapy for NSCLC is not included as a line of prior therapy if it was completed greater than 3 months prior to recurrence, provided that the patient has never received any EGFR or SFK inhibitors.
  • (Phase II only) - Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
  • (Phase II only) - Availability of tumor tissue that is at least adequate for EGFR mutational analysis. This can come from pre-existing paraffin blocks (from diagnostic biopsy or surgical resection) or patient may undergo a biopsy for research purposes.
  • (Phase II only) - Prior radiotherapy is permitted as long as there is measurable disease outside of the radiotherapy port OR clearly recurrent and growing within the radiotherapy port (see exclusion criterion 2 for details on unallowable radiotherapy).

Who cannot join

  • Women who are pregnant, breastfeeding, or have child-bearing potential and are unwilling/unable to use an acceptable method of contraception for the entire study period and for at least 4 weeks after cessation of the study drugs. All women of child-bearing potential must have a negative pregnancy test prior to first receiving protocol therapy. If the pregnancy test is positive, the patient must not receive dasatinib or erlotinib, and must not be enrolled on the study
  • Radiotherapy to ribs, sternum, pelvis, vertebrae or skull within 4 weeks prior to entering the study. (If none of these axial skeletal areas are included in the radiotherapy field, patients may have received palliative radiotherapy to long bones provided that it has ended at least 2 weeks prior to initiation of dasatinib-erlotinib therapy.)
  • Patients with any of the following cardiac problems should be excluded: (a) Uncontrolled angina, congestive heart failure, or myocardial infarction within the previous 6 months; (b) Diagnosed congenital long QT syndrome; (c) Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); (d) Prolonged [1] corrected QT interval (QTc) interval on pre-entry electrocardiogram (> 450 msec in women or >440 msec in men). If the automated reading is prolonged, the ECG should be manually over read.
  • Continued from Exclusion #4: (e) Any history of second or third degree heart block unless they currently have a pacemaker; (f) Heart rate < 50 / minute on pre-entry electrocardiogram;(g) Uncontrolled hypertension defined as systolic blood pressure > 150 or diastolic >100;(h) Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration.
  • Patients with pericardial effusion > grade 1 (by Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0).
  • Patients with pleural effusion > grade 2 (by CTCAE v3.0). A grade 3 pleural effusion that is managed by a thoracentesis or an indwelling catheter is allowable as long as supplemental oxygen is not required.
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  • Patients with any condition that impairs their ability to swallow, retain, or absorb dasatinib or erlotinib tablets are excluded. This includes any condition resulting in an inability to take oral medication, a requirement for IV alimentation, prior surgical procedures that have resulted in chronic malabsorption, or active peptic ulcer disease.
  • Patients with > grade 2 neuropathy
  • Patients with a history of pulmonary fibrosis (other than in a radiated field).
  • Patients with inflammatory bowel disease or uncontrolled chronic diarrhea.
  • Patients with a history of significant bleeding disorder unrelated to cancer, including: (a) Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease); (b) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies); (c) Ongoing or recent (</= 3 months) significant gastrointestinal bleeding, defined as clinically evident hematemesis or hematochezia requiring therapeutic intervention.
  • Known HIV-positive patients are ineligible because of the potential for pharmacokinetic interactions between dasatinib and antiretroviral therapy. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
  • Pts currently receiving any of the following medications will be excluded: (a) Any concurrent systemic anticancer therapy; (b) Any concurrent investigational agents (c) Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Pts must discontinue such drugs 7 days or more prior to starting dasatinib):i. quinidine, procainamide, disopyramide;ii. amiodarone, sotalol, ibutilide, dofetilide;iii. erythromycin, clarithromycin;iv. chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
  • Continued from Exclusion#14:v.cisapride,bepridil,droperidol,methadone,arsenic, chloroquine,domperidone,halofantrine,levomethadyl,pentamidine,sparfloxacin, lidoflazine;(d)The concomitant use of H2 blockers or proton pump inhibitors w/ dasatinib is not recommended.The use of antacids should be considered in place of H2 blockers or proton pump inhibitors in pts receiving dasatinib therapy.If antacid therapy is needed,the antacid dose should be administered at least 2 hours prior to or 2 hours after the dose of dasatinib.
  • Continued from Exclusion #15: (e)Pt may not be receiving any prohibited CYP3A4 inhibitors Potent inhibitors of CYP3A4 are prohibited during study; for such medications, a wash-out period of 7 days is required prior to starting dasatinib. Potent CYP3A4 inhibitors include: · itraconazole, ketoconazole, miconazole, voriconazole; amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir; ciprofloxacin, clarithromycin, diclofenac, doxycycline, enoxacin, imatinib, isoniazid, ketamine nefazodone, nicardipine, propofol, quinidine, telithromycin. (f) St.Johns Wort
  • The patient has received prior investigational therapy, chemotherapy, radiotherapy, or major surgery within 3 weeks of initiating study drug.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I-II Study of Dasatinib and Erlotinib in Non-Small Cell Lung Cancer

The goal of the Phase I portion of this study is to find the highest tolerable dose of the combination of dasatinib and erlotinib hydrochloride that can be given to patients with advanced solid tumors.

The goal of the Phase II portion of this study is to learn if this combination is effective when given to patients with non-small cell lung cancer.

The safety of this combination will be studied in both phases.

Read the detailed description

The Study Drugs:

Dasatinib is designed to decrease the activity of one or more proteins that are responsible for the uncontrolled growth of tumor cells. This may cause the tumor cells to die.

Erlotinib hydrochloride is designed to block the activity of a protein found on the surface of many tumor cells. Blocking the protein may control tumor growth and survival. This may stop tumors from growing.

Study Groups:

If you are found to be eligible to participate in this study, you will be assigned to a study group based on when you joined this study. Up to 6 groups of 3-6 participants each will be enrolled in the Phase I portion of the study, and up to 35 participants will be enrolled in Phase II.

If you are enrolled in the Phase I portion, the dose of dasatinib you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of dasatinib. Each new group will receive a higher dose of dasatinib than the group before it, if no intolerable side effects were seen. If intolerable side effects are seen, the next group of participants may receive the same dose level or a lower dose level. This will continue until the highest tolerable dose of dasatinib is found.

If you are enrolled in the Phase II portion, you will receive highest tolerated dose level of dasatinib that was found in the Phase I portion.

All participants will receive the same dose level of erlotinib hydrochloride. If the doctor thinks it is needed, the dose level may be lowered.

Study Drug Administration:

If you are in Phase I, on Day -3 of Cycle 1 (3 days before your first dose of study drugs), you will take erlotinib hydrochloride by mouth. On Days 1-19 of Cycle 1, you will be take dasatinib and erlotinib hydrochloride by mouth once a day. On Days 20 and 21 of Cycle 1, you will only take dasatinib by mouth once a day. Every day of Cycles 2 and beyond, you will take dasatinib and erlotinib hydrochloride by mouth once a day.

If you are in Phase II, every day you will take dasatinib and erlotinib hydrochloride by mouth once a day.

Each cycle is 21 days.

Erlotinib hydrochloride and dasatinib should be taken together at the same time every day. The tablets must be swallowed whole and may not be broken. The tablets should be taken with 1 cup (about 8 ounces) of water. Dasatinib and erlotinib hydrochloride should be taken 1 hour before or 2 hours after meals or any other drugs, and should not be taken with grapefruit juice. The entire dose must be taken at 1 time. If you vomit within 30 minutes of swallowing the tablets, the dose may be replaced if the tablets can be seen and counted. If you are currently taking St. John's Wort, you should stopping taking if for at least 5 days before taking dasatinib.

Study Visits:

At Week 1 of Cycle 1, your vital signs and weight will be measured.

At the end of Week 3 of every cycle, the following tests and procedures will be performed:

  • You will have a physical exam, including measurement of your vital signs and weight.
  • You will have a performance status evaluation.
  • Blood (about 1 tablespoon) will be drawn for routine tests
  • The amount of oxygen in your blood will be measured by a pulse oximeter.
  • You will have a chest x-ray to check the status of the disease.
  • You will be asked if you have experienced any side effects and to list any drugs you may be taking.
  • Women who are able to become pregnant must have a negative blood (about 1-2 teaspoons) or urine pregnancy test.

At the end of Week 3 of Cycles 1 and 3, you will also have an ECG.

At the end of Week 3 of every other cycle (Cycles 2, 4, 6, and so on), you will also have a chest CT scan or a whole body PET/CT (if necessary) to check the status of the disease.

Phase I PK Testing:

If you are in Phase I, you will have blood (about 2 teaspoons each time) drawn for PK testing.

  • On Day -3 of Cycle 1, blood will be drawn 5 different times.
  • On Days -2, -1, and 1 of Cycle 1, blood will be drawn 1 time.
  • On Day 19 of Cycle 1, blood will be drawn 5 times.
  • On Days 20, 21, and 22 of Cycle 1, blood will be drawn 1 time.

Length of Study:

You may stay on study for as long as you are benefitting. You will be taken off study if you experience intolerable side effects or the disease gets worse.

End-of-Study Visit:

At the end of your study participation, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

  • You will have a physical exam, including measurement of your vital signs and weight.
  • You will have a performance status evaluation.
  • Blood (about 1 tablespoon) will be drawn for routine tests.
  • The amount of oxygen in your blood will be measured.
  • You will have a chest x-ray to check the status of the disease.
  • You will have an ECG.

If you are taken off study due to unacceptable side effects, you will be called and asked about any side effects until the side effect gets better or becomes stable.

Long-Term Follow-Up:

After the end-of-study visit, you will be contacted every 3-4 months for 1 year to collect information about how you are doing. You (or your family members or designees) may be contacted by telephone or during clinic visits. If you are called, this will take about 5 minutes.

This is an investigational study. Dasatinib is FDA approved and commercially available for the treatment of acute lymphoid and chronic myeloid leukemia. Erlotinib hydrochloride is FDA approved and commercially available for the treatment of non-small cell lung cancer. The use of this combination in this study is investigational.

Up to 59 patients will take part in this study. All will be enrolled at MD Anderson.

Being tested
Dasatinib, Erlotinib
Keywords
Advanced Solid Tumors, Advanced Cancer, Non-Small Cell Lung Cancer, NSCLC, Solid Tumor Malignancy, Dasatinib, BMS-354825, Sprycel®, Erlotinib, Erlotinib hydrochloride, Tarceva, OSI-774
Medical subject headings
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DasatinibDrug

    Also called BMS-354825, Sprycel®

    Starting dose of 70 mg by mouth daily for 21 day cycle.

  • ErlotinibDrug

    Also called Erlotinib hydrochloride, Tarceva, OSI-774

    150 mg by mouth daily every 21 day cycle.

Study groups in NCT00826449
Study groupRoleWhat they receive
Phase IExperimentalDasatinib + Erlotinib
Receives: Drug: Dasatinib; Drug: Erlotinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I: Maximum Tolerable Dose (MTD) of Dasatinib Given With Erlotinib Hydrochloride

    MTD defined as the highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). Dose-limiting toxicity (DLT) defined using NCI Common Terminology Common Terminology Criteria for Adverse Events (CTCAE) version 3 as: grade 3 or higher non-hematologic toxicity (excluding initial nausea and vomiting), grade 4 neutropenia, febrile neutropenia, or grade 4 thrombocytopenia. Grade 3-4 nausea and vomiting that cannot be controlled within 2 weeks with anti-emetics considered a DLT.

    Measured: Baseline and at Day 21

Secondary outcomes (2)

  1. Phase II: Number of Participant With Response According to Response Evaluation Criteria in Solid Tumors (RECIST)

    Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria. Patients who have a partial or complete response or stable disease are defined as progression free. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least 30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD; Progressive Disease (PD): At least 20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase.

    Measured: 12 Weeks

  2. Phase II: Progression-Free Survival (PFS) Rate

    A modified Thall, Simon, and Estey (1995) design used in the phase II study to monitor the proportion of patients with NSCLC who are alive and progression free (PFS) at twelve weeks after commencing treatment with dasatinib and erlotinib.

    Measured: 12 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jan 2009 (estimated)
  2. Study startFeb 2009
  3. Primary completionJun 2014
  4. Study completionJun 2014

Resources

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
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00826449
Sponsor's protocol ID
2008-0353
Other IDs
NCI-2012-01653
Status last verified
May 2016
First submitted
20 Jan 2009
Last updated
28 Jun 2016
Data monitoring committee
No

Publications

  • Gold KA, Lee JJ, Harun N, Tang X, Price J, Kawedia JD, Tran HT, Erasmus JJ, Blumenschein GR, William WN, Wistuba II, Johnson FM. A phase I/II study combining erlotinib and dasatinib for non-small cell lung cancer. Oncologist. 2014 Oct;19(10):1040-1. doi: 10.1634/theoncologist.2014-0228. Epub 2014 Aug 28.

    PubMed 25170013

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Dasatinib and Erlotinib in people with Lung Cancer and Non-Small Cell Lung Cancer, run by M.D. Anderson Cancer Center 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 25 inclusion and 16 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 28 Jun 2016. 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 21 Oct 2015). 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?

Phase I: Maximum Tolerable Dose (MTD) of Dasatinib Given With Erlotinib Hydrochloride (time frame: Baseline and at Day 21). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00826449, which also lists 1 linked publication.

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 28 Jun 2016.

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