| Eligibility |
Inclusion Criteria:
1. Written informed consent and HIPAA authorization for release of personal health
information prior to registration. NOTE: HIPAA authorization may be included in the
informed consent.
2. Age = 18 years at the time of consent.
3. Histologically or cytologically confirmed non-squamous, non-small cell lung cancer
4. Locally advanced or metastatic disease.
5. Patients must have one of the following:
- NSCLC which harbours EGFR Exon 19 deletion.
- NSCLC which harbours EGFR L858R mutation. EGFR deletion/mutation must be
documented by a Clinical Laboratory Improvement Amendments (CLIA) certified test
(either from tissue or ctDNA from blood is allowed)
6. The patient must have received a third-generation EGFR TKI treatment, regardless of
the T790M status. The patient must have progressed on osimertinib, or an equivalent
third-generation EGFR TKI with regulatory approval.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix A)
8. At least one lesion, not previously irradiated and not chosen for biopsy during the
study screening period, that can be accurately measured at baseline at equal or
greater than 10mm in the longest dimension by RECIST 1.1.
9. Ability to take pills or capsules by mouth
10. Prior treatment with cytotoxic chemotherapy or immunotherapy is allowed. Up to 3 lines
of prior therapy is allowed.
11. Patients must have adequate hematologic, coagulation, hepatic, and renal function. All
laboratory tests must be obtained less than 4 weeks from study entry. This includes:
- ANC >/= 1,500/mm3
- platelet count >/=100,000/mm3
- HgB = 9 g/dL
- Creatinine = 1.5x ULN or creatinine clearance (measured via 24-hour urine
collection) =40 mL/minute (that is, if serum creatinine is >1.5 times the ULN, a
24-hour urine collection to calculate creatinine clearance must be performed).
- Total Serum Bilirubin = 1.5 x ULN (Patients with known Gilbert Syndrome, a total
bilirubin = 3.0 x ULN, with direct bilirubin = 1.5 x ULN)
- SGOT, SGPT = 3 X ULN if no liver metastasis present
- SGOT, SGPT = 5 X ULN if liver metastasis present
12. Females of childbearing potential must not be breast feeding and must have a negative
serum or urine pregnancy test within 7 days of starting of treatment. The patient must
agree to use adequate contraception for a minimum of two weeks prior to receiving
study medication until 3 months after discontinuation of the study medication.
Acceptable methods of contraception include total and true sexual abstinence, hormonal
contraceptives that are not prone to drug-drug interactions (IUS Levonorgestrel Intra
Uterine System (Mirena), Medroxyprogesterone injections (Depo-Provera)), copper-banded
intra-uterine devices, and vasectomized partner. All hormonal methods of contraception
should be used in combination with the use of a condom by their sexual male partner.
Females of childbearing potential are defined as those who are not surgically sterile
(i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or
postmenopausal (defined as 12 months with no menses without an alternative medical
cause). Women will be considered post-menopausal if they have been amenorrheic for the
past 12 months without an alternative medical cause. The following age-specific
requirements must also apply: Women < 50 years old: they would be considered
post-menopausal if they have been amenorrheic for the past 12 months or more following
cessation of exogenous hormonal treatments. The levels of Luteinizing Hormone (LH) and
Follicle-Stimulating Hormone (FSH) must also be in the post-menopausal range (as per
the institution). Women = 50 years old: they would be considered post-menopausal if
they have been amenorrheic for the past 12 months or more following cessation of all
exogenous hormonal treatments, or have had radiation-induced oophorectomy with the
last menses > 1 year ago, or have had chemotherapy-induced menopause with >1 year
interval since last menses, or have had surgical sterilization by either bilateral
oophorectomy or hysterectomy.
13. Non-sterilized males who are sexually active with a female partner of childbearing
potential must use adequate contraception for the duration of the study and 3 months
after the last dose of study medication. Adequate contraception methods include: birth
control pills (e.g. combined oral contraceptive pill), barrier protection (e.g. condom
plus spermicide, cervical/vault cap or intrauterine device), and abstinence. Patients
should not father a child for 6 months after completion of the study medication.
Patients should refrain from donating sperm from the start of dosing until 6 months
after discontinuing the study medication. If male patients wish to father children
they should be advised to arrange for freezing of sperm samples prior to the start of
the study medication.
14. Participants of childbearing potential who are sexually active and their partners must
agree to abstain from heterosexual activity or to use 2 forms of effective methods of
contraception. Non-sterilized males who are sexually active with a female partner of
childbearing potential must use adequate contraception for the duration of the study
and for 3 months after the last dose of study treatment. Patients should not father a
child during the study or for 6 months after completion of study treatment. Patients
should refrain from donating sperm from the start of dosing until 6 months after
discontinuing the study treatment. Two contraception methods can be comprised of two
barrier methods, or a barrier method plus a hormonal method. See below for options:
Acceptable non-hormonal birth control methods:
- Total sexual abstinence ie, refrain from any form of sexual intercourse in line with
the patients' usual and/or preferred lifestyle. Abstinence must be for the total
duration as described above. Periodic abstinence (eg, calendar ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of
contraception.
- Vasectomised sexual partner PLUS male condom. With participant assurance that partner
received post-vasectomy confirmation of azoospermia.
- Tubal occlusion PLUS male condom
- Intrauterine Device PLUS male condom. Provided coils are copper-banded.
Acceptable hormonal methods:
- Etonogestrel implants (eg, Implanon®, Norplant®) PLUS male condom
- Normal and low dose combined oral pills PLUS male condom
- Hormonal shot or injection (eg, Depo-Provera) PLUS male condom
- Intrauterine system device (eg, levonorgestrel-releasing intrauterine system -
Mirena®) PLUS male condom
Exclusion Criteria:
1. Previous treatment with other aurora kinase inhibitors.
2. Spinal cord compression or brain metastases unless asymptomatic or stable for at least
2 weeks prior to start of study treatment.
3. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 (with the
exception of alopecia grade 2) at the time of starting study treatment.
4. Any evidence of severe or uncontrolled systemic diseases. Screening for chronic
conditions is not required.
5. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to
swallow the formulated product or previous significant bowel resection that would
preclude adequate absorption of osimertinib.
6. Males and females of reproductive potential who are not using and effective method of
birth control and females who are pregnant or breastfeeding or have a positive (urine
or serum) pregnancy test prior to study entry.
7. Judgment by the investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions and requirement.
8. Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc using Fridericia's formula) > 470 msec,
except in patients with existing bundle block, which artificially prolongs QTc.
- Any clinically important abnormalities in rhythm, conduction or morphology of
resting ECG e.g., complete left bundle branch block, third degree heart block,
second degree heart block, PR interval >250msec
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic
events such as heart failure, hypokalemia, congenital long QT syndrome, family
history of long QT syndrome or unexplained sudden death under 40 years of age in
first degree relatives or any concomitant medication known to prolong the QT
interval.
- The patient has experienced any arterial thromboembolic events, including but not
limited to myocardial infarction, transient ischemic attack, cerebrovascular
accident, or unstable angina, within 6 months prior to first dose of protocol
therapy.
- The patient has uncontrolled or poorly-controlled hypertension (>160 mmHg
systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical
management.
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