Inclusion Criteria:
1. Written informed consent and HIPAA authorization for release of personal health
information. NOTE: HIPAA authorization may be included in the informed consent or
obtained separately.
2. Age ≥ 18 years at the time of consent. 3. ECOG Performance Status of ≤ 1. 4. Subjects with histologically or cytologically confirmed advanced solid tumors which
have progressed after standard therapy(ies), intolerant to standard therapy, refused
standard therapy or for which no standard therapy(ies) exist. Furthermore, the tumor
targeted for injections should be:
1. A non-visceral tumor, a metastatic lymph node, a metastasis from a visceral solid
tumor provided the lesion is extravisceral, or a cutaneous tumor. Visceral tumors
will not be treated.
2. The tumor must be measurable as per RECIST criteria.
3. The tumor should be directly accessible for injection or accessible with the use
of ultrasound/CT guidance.
4. The tumor identified for injection should be selected so local control could
potentially provide benefit to the patient.
5. 80% of the tumor must be accessible for injection with X-PACT (assessed by the
treating physician)
6. The tumor must be superficial and not exceed a depth of 5 cm.
7. Eye or brain tumors will not be treated.
5. A patient with prior brain metastasis may be considered if they have completed their
treatment for brain metastasis at least 4 weeks prior to day 1 of treatment, have been
off of corticosteroids for ≥ 2 weeks, and brain metastases are asymptomatic.
6. The study site Radiation Oncologist Investigator/sub-investigator has determined
additiional radiation delivered via X-PACT is appropriate given patient's prior
radiation exposure. The treating Radiation Oncologist will review all prior radiation
received to the proposed site of X-PACT treatment and assess the potential for
unacceptable toxicity to the site or local organ(s) using QUANTEC.
7. All toxicities from prior therapy should be ≤Grade 1 before start of study treatment.
All radiation associated toxicities must have completely resolved to be considered for
inclusion into the study.
8. Demonstrate adequate organ function as defined in the table below:
Hematological:
White blood cell (WBC) ≥ 3 x 109/L Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
Platelet Count ≥ 100 x 109/L Hemoglobin (Hgb) ≥ 8 g/dL2. Renal:
Serum creatinine OR Creatinine clearance ≤ 1.5 x upper limit of normal (ULN) OR, in
patients with a serum creatinine 1.5 x ULN, ≥ 60 mL/min as measured by a 24-hour urine
collection or estimated by the Cockcroft and Gault formula. Hepatic:
Total bilirubin ≤ 1.5 × ULN (in patients with known Gilbert Syndrome a total bilirubin
≤3.0× ULN with direct bilirubin ≤1.5 X ULN) Aspartate aminotransferase (AST) ≤ 2.5 ×
ULN (or ≤ 5 if liver metastases are present) Alanine aminotransferase (ALT) ≤ 2.5 ×
ULN (or ≤ 5 if liver metastases are present)
Coagulation:
International Normalized Ratio (INR) ≤ 1.5. 9. Females of childbearing potential (FCBP) must have a negative serum pregnancy test
within 3 days prior to day 1 of treatment. NOTE: Females are considered of
childbearing potential unless they are surgically sterile (have undergone a
hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are
postmenopausal (at least 12 consecutive months with no menses without an alternative
medical cause).
10. FCBP must be willing to use a highly effective contraceptive method (i.e., achieves a
failure rate of <1% per year when used consistently and correctly) from the time of
informed consent until 28 days after treatment discontinuation. Contraceptive methods
with low user dependency are preferable but not required (see table below, adapted
from:
http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2
014_09_HMA_CTFG_Contraception.pdf)
Highly Effective Birth Control Methods:
- - combined (estrogen and progestogen containing) hormonal contraception associated
with inhibition of ovulation.
- - progestogen-only hormonal contraception associated with inhibition of ovulation.
- - intrauterine device (IUD)
- intrauterine hormone-releasing system (IUS)
- vasectomised partner.
11. Male patients must be willing to use condoms from the time of informed consent until
28 days after treatment discontinuation. For a non-pregnant FCBP partner,
contraception recommendations should also be considered.
12. As determined by the enrolling physician, ability of the patient to understand and
comply with study procedures for the entire length of the study. 13. Patient is expected to have a life expectancy of at least 4 months. 14. If the proposed site of treatment with X-PACT had prior exposure to curative-intent
radiation, the patient may be entered into the trial with the following provisions
satisfied.
- - There is at least a 6 month wash out period from the last date radiation was
received to assess for radiation toxicity.
- - If there was previous radiation toxicity at the proposed site of X-PACT, the
toxicity resolved at least three months ago and the site did not involve a major
organ.
- - The site investigator in addition to the radiation oncologist (as a part of
criterion #6) has fully reviewed the subject's radiation history, has examined
the area for radiation toxicity and assessed the cumulative dose for either 5 or
7 X-PACT treatments and determined they will not pose additional risk for
radiation toxicity or re-activate any other previous toxicity.
Exclusion Criteria:
Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use
while the mother is being treated on study.)
2. Prior exposure to methoxsalen. 3. History of any of the following:
1. Idiosyncratic or hypersensitivity reactions to any psoralen compounds or any
of their excipients. 2. Light sensitive disease state. 3. Disease associated with photosensitivity including lupus erythematosus,
porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria,
xeroderma pigmentosum and albinism. 4. Aphakia. 4. History of idiosyncratic or hypersensitivity reactions to any of the phosphor
device components. 5. Known diagnosis of human immunodeficiency virus (HIV), hepatitis B or hepatitis C
infection (NOTE: testing not required)
6. Active infection requiring systemic therapy (NOTE: at discretion of investigator,
patients with uncomplicated urinary tract infections may be eligible.)
7. Has a known additional other primary malignancy that is active and/or progressive
requiring treatment; exceptions include basal cell skin cancer, in situ cervical
or bladder cancer, or other cancer for which the patient has been disease-free
for at least five years.
8. Systemic anti-cancer treatment within 28 days (or 5 half-lives, whichever is
shorter) prior to day 1 of treatment. 9. Treatment with any investigational drug within 5 half-lives or 28 days, whichever
is shorter (or if half-life is unknown, within 28 days) prior to day 1 of
treatment. 10. Impaired cardiac function or clinically significant cardiac diseases, including
any of the following:
1. Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial
fibrillation are not excluded)
2. Uncontrolled hypertension (systolic BP > 170 mmHg or diastolic BP > 105 mmHg
at screening) despite two concomitant antihypertensive therapies.
3. Acute myocardial infarction or unstable angina ≤ 6 months prior to day 1 of
treatment. 4. New York Heart Association Class III or IV congestive heart failure (
11. Other uncontrolled intercurrent illness including, but not limited to, ongoing or
active infection, or psychiatric illness/social situations that would limit
compliance with study requirements as determined by the investigator.
12. The tumor identified for treatment has a volume greater than 500 cc (Soft Tissue
Sarcoma only). All other tumor types may have a maximum volume of 300 cc. 13. Receiving or planned use of corticosteroids. Subjects will require a one-week
washout period from prior corticosteroid use. Inhaled or topical steroids are
permitted.
14. Subjects with active autoimmune disease requiring 10 mg or greater of prednisone
and/or biologic agents.
15. Subjects with a history of pancreatitis or elevated baseline serum lipase without
otherwise specified etiology.
