| Eligibility |
Inclusion Criteria (Eligibility for TIL Evaluation):
1. Platinum resistant high grade serous ovarian, fallopian tube, or primary peritoneal
cancer.
2. Tumor is suitable for harvest (i.e., lesion to be harvested for TIL evaluation has a
total volume of =1cm3) or patient has previously undergone tumor harvest under other
REB approved studies involving clinical evaluation of TILs.
3. If tumor harvest is required, subject must be a suitable surgical candidate in the
opinion of the operating surgeon.
4. Patient age: = 18 years.
5. Clinical performance status of ECOG 0 or 1.
6. Life expectancy > 5 months from the date of consent for TIL evaluation.
7. Ability to understand and has signed the Pre-Screening Consent Form.
8. Patients are willing to be tested for transmissible diseases (active Hepatitis B (HBV)
or Hepatitis C (HCV), human immunodeficiency virus (HIV), Human T-Cell Lymphotropic
Virus (HTLV), Herpes Simplex Virus (HSV), Cytomegalovirus (CMV), Syphilis (with West
Nile Virus only tested between May 1st and November 30th)
9. Confirmation that the Translational Immunotherapy Lab is able to process the specimen
10. If there is a history of allergy to penicillin, gentamycin, streptomycin, or
anti-fungals, the ability to generate TILs should first be confirmed with the cell
manufacturing lab (i.e., Translational Immunotherapy Laboratory).
Inclusion Criteria (Eligibility for Treatment):
1. Prior to the performance of any study-specific procedure, the subject has signed and
dated the informed consent form, approved by a Research Ethics Board (REB), after the
nature of the study has been explained and the subject has had the opportunity to ask
questions.
2. Recurrent platinum resistant high grade serous ovarian, fallopian tube, or primary
peritoneal cancer, with evidence of disease progression from previous line of
treatment.
3. Measurable disease by RECIST 1.1.
4. Subjects should have no brain metastases. Note if brain metastases are present, these
lesions must undergo definitive treatment with surgery and/or radiation at least 30
days prior to the first dose of lymphodepleting chemotherapy. If in the opinion of the
PI or his designee the lesion(s) no longer represents active disease, the subject will
be considered eligible.
5. Clinical performance status of ECOG 0 or 1.
6. Life expectancy > 3 months from the date of consent for TIL treatment.
7. Laboratory analyses of tumor-infiltrating lymphocytes (TILs) from the subject must
demonstrate that the TILs are suitable for use in protocol treatment (performed by the
Translational Immunotherapy Laboratory, Princess Margaret Cancer Centre)
8. More than 30 days has elapsed since any prior systemic therapy at the time of the cell
infusion. All subjects' toxicities must have recovered to a CTCAE grade 1 or less;
however, patients with residual CTCAE grade 2 neuropathy from previous
carboplatin/taxol treatment will not be excluded. Subjects may have undergone minor
surgical procedures within the past 3 weeks, as long as all toxicities have recovered
to CTCAE grade 1 or less or as specified in the inclusion criteria listed above.
9. Adequate organ function as defined by the following criteria:
1. Serum ALT = 2.5 x upper limit of normal (ULN) (for patients with liver
metastases, serum ALT = 3 x ULN;
2. Serum AST = 2.5 x upper limit of normal (ULN) (for patients with liver
metastases, serum AST = 3 x ULN;
3. Total serum bilirubin = 2xULN (patients with Gilbert's Syndrome - direct serum
bilirubin = 2 x ULN);
4. Absolute neutrophil count (ANC) = 1.5x109/L;
5. Platelets =100x109/L;
6. Hemoglobin = 90 g/L for female;
7. Alkaline phosphatase = 2 x ULN;
8. Serum creatinine within normal institutional limits OR serum creatinine clearance
= 60 mL/min/1.73m2 for patients with creatinine levels above institutional
normal;
9. Serum lipase= 1.5 x ULN;
10. Serum amylase = 1.5 x ULN
10. Women of child-bearing potential must have a negative pregnancy test. Acceptable birth
control failure rate of less than or equal to 1% when used consistently and correctly
such as implants, injectables, combined oral contraceptives, double barrier, some
intrauterine devices (IUDs), sexual abstinence or vasectomized partner. Subjects are
considered to be not of child bearing potential if they are considered to be
post-menopausal or surgically sterilized (e.g. tubal occlusion, hysterectomy,
bilateral salpingectomy. Women who have been amenorrheic for 12 or more months are
still considered to be of childbearing potential if the amenorrhea is possibly due to
prior chemotherapy, anti-estrogens, ovarian suppression or any other reversible
reason.
Exclusion Criteria:
1. Subjects with ongoing or prior use systemic steroid therapy within 4 weeks before the
TILs infusion will be excluded. Use of topical, intranasal and inhaled
corticosteroids, or systemic corticosteroids at physiologic doses are allowed. Oral
steroid use as premedication to prevent allergic reactions to radiologic contrast is
allowed.
2. Subjects cannot be HIV positive.
3. Subjects cannot have active hepatitis B or hepatitis C, syphilis, or Human T-Cell
Lymphotropic Virus (HTLV).
4. The number of prior lines of chemotherapy is not limited. However, if the subject has
had =3 lines of prior chemotherapy for platinum refractory or platinum resistant
disease, documentation of a response to one of these lines is required. Response can
be defined by RECIST 1.1 or CA125 as defined by the modified GCIG criteria (See
Section 11).
5. The subject cannot have any active systemic infections, coagulation disorders or other
active major medical illnesses of the cardiovascular, respiratory or immune system,
uncontrolled psychiatric disorders, or other conditions that may affect compliance
with the trial.
6. The subject must have no active underlying cardiac illnesses defined by positive
stress test, LVEF<40% or ongoing life-threatening arrhythmias (i.e., for patients
older than 60 years of age or otherwise clinically indicated).
7. Subjects who have a prolonged history of cigarette smoking or symptoms of respiratory
dysfunction will be excluded if they have an abnormal pulmonary function test as
evidenced by a FEV1 < 60% predicted.
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