| Eligibility |
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 0-1 within 14 days prior to registration.
4. Locally advanced esophageal adenocarcinoma or proximal gastric adenocarcinoma or
metastatic adenocarcinoma originating from esophagus, GE junction, or proximal stomach
who progress/recur beyond 2 months of receiving a platinum- containing regimen
NOTE: Patients can be pre-screened for study at any time including after surgical
resection for locally advanced esophageal cancer, at presentation with metastatic
disease and potentially during chemotherapy and radiation prior to surgery.
5. A subject with symptomatic brain metastasis may be considered if they have completed
their treatment for brain metastasis at least 4 weeks prior to study registration,
have been off of corticosteroids for = 2 weeks, and are asymptomatic. Patients with
asymptomatic brain mets that are untreated will be allowed.
6. Must not have received more than 1 prior line of chemotherapy in the metastatic
setting (could have received immunotherapy, VEGF directed therapy, and/or trastuzumab
which does not count as chemotherapy).
7. One of the following genetic results is required for eligibility:
- High LOH in tissue OR
- HR mutation in tissue OR
- Germline mutation (blood)
NOTE: Mutations, deletions or loss by fusions are the acceptable alterations in HR
genes as long as they are deleterious. Patients are eligible if they have a mutation
in pre-specified HR genes BRCA1/2, PALB2, ATM, BARD1, BRIP1, CDK12, CHEK2, FANCA,
RAD51, RAD51B, RAD51C, RAD51D, RAD54L, NBN, ARID1A and GEN1. Deleterious mutations in
HR genes are defined as those that have been previously characterized to be
loss-of-function/pathogenic/or likely pathogenic as specified per the following
databases: Clinvar, OncoKB, or BRCAExchange. Mutations or small insertions or
deletions that results in truncation, frameshift, stop codon loss, or stop codon gain
will also be considered deleterious irrespective of their presence in the
aforementioned databases unless previously characterized to be benign. Copy number
losses or disruption by fusion will also be considered deleterious irrespective of
their presence in the aforementioned databases. Gene amplifications or variants of
unknown significance will not be eligible for inclusion.
NOTE: Genetic testing results from a CLIA certified lab that confirm one of the
following: high LOH in tissue, HR mutation in tissue or germline mutation in blood are
required and can be used to meet eligibility. Even if subject has met eligibility with
one of the criteria above, results from the other analysis is required if available.
If prior genetic results are not available, subject must have archival tissue or fresh
tissue (by new biopsy) for testing. Both primary tumor tissue and metastatic site
sample biopsies are allowed. Blood will also be required for germline mutation
analyses. Central confirmation of all results will be performed but are not mandated
for eligibility. If a subject has met eligibility with prior genetic results but does
not have sufficient archival tissue for central confirmation, a biopsy is not
required.
8. Presence of measurable disease by RECIST v1.1, defined as:
- Tumor lesions that must be accurately measured in at least one dimension (longest
diameter in the plane of measurement is to be recorded) with a minimum size of:
- 10 mm by CT scan (CT scan slice thickness no greater than 5 mm)
- 10 mm caliper measurement by clinical exam (lesions which cannot be
accurately measured with calipers should be recorded as non-measurable)
- 20 mm by chest X-ray
- Malignant lymph nodes: To be considered pathologically enlarged and measurable, a
lymph node must be = 15 mm in short axis when assessed by CT scan (CT scan slice
thickness recommended to be no greater than 5 mm). At baseline and in follow-up,
only the short axis will be measured and followed.
9. Prior cancer treatment must be completed at least 14 days prior to registration and
the subject must have recovered from all reversible acute toxic effects of the regimen
(other than alopecia) to = Grade 1 or baseline.
10. Demonstrate adequate organ function as defined in the table below; all screening labs
to be obtained within 14 days prior to registration.
- Absolute Neutrophil Count (ANC) = 1.5 K/mm3
- Hemoglobin (Hgb) = 9 g/dL
- Platelet Count (Plt) = 100 K/ mm3
- Creatinine = 1.5 X upper limit of normal (ULN)
- Bilirubin = 1.5× ULN ((=2.0 in patients with known Gilberts syndrome))
- Aspartate aminotransferase (AST) = 2.5× ULN*
- Alanine aminotransferase (ALT) = 2.5 × ULN*
11. Females of childbearing potential must have a negative pregnancy test within 7 days
prior to study treatment. Urine or serum ßhCG if clinically appropriate. If a urine
test is done and it is positive or cannot be confirmed as negative, a serum pregnancy
test will be required. NOTE: Females are considered of child bearing potential unless
they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation,
or bilateral oophorectomy) or they are naturally postmenopausal for at least 12
consecutive months.
12. Females of childbearing potential must be willing to abstain from heterosexual
intercourse or use adequate contraception as described in the protocol. Males must be
willing to abstain from heterosexual intercourse or use adequate contraception as
described in the protocol.
13. Participants must agree to not breastfeed during the study or for 30 days after the
last dose of study treatment.
14. As determined by the enrolling physician or protocol designee, ability of the subject
to understand and comply with study procedures for the entire length of the study.
15. Participant must agree to not donate blood during the study or for 90 days after the
last dose of study treatment.
Exclusion Criteria:
1. Prior therapy with a PARP inhibitor
2. Disease progression during first 2 months of standard dose platinum-based chemotherapy
(platinum refractory). This excludes low dose platinum based therapy that is given in
a chemotherapy-radiation regimen for locally advanced esophageal cancer.
3. Participant must not be simultaneously enrolled in any other interventional clinical
trial.
4. Participant must not have had major surgery = 3 weeks prior to initiating protocol
therapy and participant must have recovered from any surgical effects.
5. Participant must not have received investigational therapy = 4 weeks, or within a time
interval less than at least 5 half-lives of the investigational agent, whichever is
shorter, prior initiating protocol therapy.
6. Participant has had radiation therapy encompassing >20% of the bone marrow within 2
weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
7. Participant must not have a known hypersensitivity to niraparib components or
excipients including tartrazine.
8. Participant must not have received a transfusion (platelets or red blood cells) = 4
weeks prior to initiating protocol therapy.
9. Participant must not have received colony stimulating factors (e.g., granulocyte
colony-stimulating factor, granulocyte macrophage colony stimulating factor, or
recombinant erythropoietin) within 4 weeks prior initiating protocol therapy.
10. Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due
to prior chemotherapy that persisted > 4 weeks and was related to the most recent
treatment.
11. Participant must not have any known history of myelodysplastic syndrome (MDS) or acute
myeloid leukemia (AML).
12. Participant must not have a serious, uncontrolled medical disorder, nonmalignant
systemic disease, or active, uncontrolled infection. Examples include, but are not
limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial
infarction, uncontrolled major seizure disorder, unstable spinal cord compression,
superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining
informed consent.
13. No active secondary cancer
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