Lazanda in Cancer Patients Receiving Palliative Radiation

This is a Phase II, single-center, single-arm, Open-Label Study to Evaluate Lazanda in Cancer
Patients Receiving Palliative Radiation.

The primary objective of this study is to assess the change in patient reported positional
pain intensity (PI) as measured by an 11-point numerical rating scale (NRS-11) in cancer
patients with bone metastases assessed at a simulation visit and each subsequent daily
palliative radiation fraction. The primary objective will be measured using the pain
intensity difference (PID) of the NRS-11 from the time of laying down on the hard surface (0
minutes/ PI0) to the 15 minutes after laying down on the hard surface timepoint at baseline
(the simulation visit) and at each subsequent study visit (PID15= PI0- PI15).

Study participants will be recruited across all oncology disease teams. Potential
participants will be identified in weekly palliative care or disease team patient triage
meetings. In order to meet eligibility for participation, a patient must be greater than or
equal to 18 years old, have histologically-confirmed cancer with symptomatic bone metastases,
an Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 3, and
are planned to receive hypofractionated palliative radiation less than or equal to 10
fractions. Qualifying subjects must be opioid-tolerant, defined as greater than or equal to
60mg morphine or equivalent, and be on a stable dose of oral opioids for greater than or
equal to 1 week. Stable baseline opioid dosage is defined as a dosage that does not fluctuate
by more than 50% from the average dosage over one week prior to screening. Patients must also
be on a stable dose of adjuvant pain therapies for one week prior to screening. Patients will
be excluded if they are receiving or have received another investigational agent within 30
days or monoamine oxidase inhibitor within 14 days prior to Lazanda administration, have
known hypersensitivity to fentanyl or opioids, have known, planned interventional procedures
such as surgery that may affect study outcomes, are pregnant or nursing, have a disorder or
current medication use likely to adversely affect normal functioning of the nasal mucosa,
have uncontrolled or rapidly escalating background pain, or are medically unstable, require
immobilization with a thermoplastic mask for radiation treatment.

Upon confirmation of all eligibility criteria, the subject will be enrolled. Each enrolled
subject will undergo a baseline evaluation on a mock hard surface within 1 week prior to the
time of CT simulation, to establish baseline NRS pain scores.

Subject will receive Lazanda at their mock hard surface visit , radiation simulation visit
and again as pre-medication prior to each radiation treatment (fraction), for an estimated
treatment period of 10 days based on the patient's radiation treatment plan. Lazanda will be
self-administered intranasally by subjects participating in this study.

NRS pain scores will be collected at three time points at baseline : 15 minutes prior to
laying on the hard surface (T-15), at the time of laying on the hard surface (T0), and at 15
minutes after laying on the hard surface(T+15). Exact time of each pain score rating will
also be collected.

After the mock visit subject will then undergo radiation therapy simulation procedures
(within approximately 2 weeks of radiation therapy) followed by hypofractionated radiation
therapy, according to University of California, San Diego (UCSD) Radiation Oncology standard
procedure and treatment plan determined by the subject's radiation oncologist. During
radiation simulation and daily during each visit to the radiation center for
hypofractionation delivery, subjects will have vital signs and weight collected. An ECOG
performance status will also be assessed daily during radiation therapy. At the time of
radiation simulation and daily during radiation therapy, subjects will complete the BPI-sf ,
Medication Use Diary, Laxation Diary, and Nausea/Vomiting Diary. As with the mock hard
surface evaluation, NRS pain scores will also be collected at three time points during each
visit to the radiation center.

Subjects will receive study drug, Lazanda at 100mcg dose, 15 minutes prior to simulation
(T-15) at the radiation therapy simulation visit. Lazanda dose titration will follow the
guidelines as indicated in the product package insert from the radiation simulation visit
through the end of radiation therapy.

Subjects will undergo a post treatment follow-up period after completion of their radiation
therapy. During this follow-up period, subjects will complete the BPI-sf, Medication Use
Diary, Laxation Diary , and Nausea/Vomiting Diary daily for 2 days.

Inclusion Criteria:

1. Patient has the ability to understand and the willingness to sign a written informed
consent.

2. Pathologically-confirmed solid tumor or hematologic malignancy with symptomatic bone
metastases.

3. Patient is planned to receive hypofractionated palliative radiation ≤ 10 fractions.

4. Patient must be opioid-tolerant (greater than or equal to 60mg morphine or equivalent)
and on a stable dose of oral opioids for greater than or equal to 1 week. Stable
baseline opioid dosage defined as a dosage that does not fluctuate by more than 50%
from the average dosage over one week prior to screening.

5. Patient must be on a stable dose of adjuvant pain therapies for one week prior to
screening (i.e. steroids, NSAIDs, anticonvulsants, pharmaceutical cannabinoids,
tricyclic antidepressants).

6. Patient is ≥ 18 years of age.

7. Both men and women of all races and ethnic groups are eligible for this trial.

8. ECOG Performance Status ≤ 3

9. Women of child-bearing potential and men with partners of child-bearing potential must
agree to use adequate contraception (hormonal or barrier method of birth control;
abstinence) prior to study entry, for the duration of study participation, and for 28
days following completion of therapy. Should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately

- A woman of child-bearing potential is any female (regardless of sexual
orientation, having undergone a tubal ligation, or remaining celibate by choice)
who meets the following criteria:

- Has not undergone a hysterectomy or bilateral oophorectomy; or

10. Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has
had menses at any time in the preceding 12 consecutive months)Women of child-bearing
potential has negative pregnancy test prior to initiating study drug dosing.

Exclusion Criteria:

1. Patient is currently receiving or has received another investigational agent within 30
days or monoamine oxidase inhibitor within 14 days prior to Lazanda administration.

2. Patients who require immobilization with a thermoplastic mask for radiation treatment.

3. Patient is planned to receive interventional procedures (i.e. surgery) that may affect
study outcomes.

4. Patient has a history of hypersensitivity to fentanyl or opioids.

5. Patient is pregnant or nursing. There is a potential for congenital abnormalities and
for this regimen to harm nursing infants.

6. Patient is being treated with oxymetazoline for allergic rhinitis or has a disorder or
current medication use likely to adversely affect normal functioning of the nasal
mucosa.

7. Patient has uncontrolled or rapidly escalating background pain.

8. Patient has bradyarrhythmia.

9. Patient is considered medically unstable.

10. Patient is thought to be at risk for misuse, abuse, addiction or overdose for Schedule
II controlled substance, as evidenced by the following:

1. An Opioid Risk Tool (ORT) score of greater/less than or equal to 8.

2. A review of the California Prescription Control Monitoring Program (PDMP)
Controlled Substance Utilization Review and Evaluation System (CURES) report
demonstrates multiple prescribing providers and/or multiple pharmacies in the
last 30 days. The CURES report will also be used to verify opioid use, opioid
dose, and current prescribing providers.