Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This phase II Pediatric MATCH trial studies how well olaparib works in treating patients with
solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with defects in deoxyribonucleic
acid (DNA) damage repair genes that have spread to other places in the body (advanced) and
have come back (relapsed) or do not respond to treatment (refractory). Olaparib is an
inhibitor of PARP, an enzyme that helps repair DNA when it becomes damaged. Blocking PARP may
help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors
are a type of targeted therapy.
Phase
Phase 2
Funding Agency/Sponsor
National Cooperative Group
Disease
Pediatric Cancer
Enrollment Eligibility
Inclusion Criteria:
- Patient must have enrolled onto APEC1621SC (NCT03155620) and must have been given a
treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621H
based on the presence of an actionable mutation
- Patients must be >= than 12 months and =< 21 years of age at the time of study
enrollment
- Patients must have a body surface area >= 0.65 m^2 at enrollment
- Patients must have radiographically measurable disease at the time of study
enrollment; patients with neuroblastoma who do not have measurable disease but have
iobenguane (MIBG) positive (+) evaluable disease are eligible; measurable disease in
patients with CNS involvement is defined as tumor that is measurable in two
perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than
one slice
- Note: The following do not qualify as measurable disease:
- Malignant fluid collections (e.g., ascites, pleural effusions)
- Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
- Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
- Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
- Previously radiated lesions that have not demonstrated clear progression
post radiation
- Leptomeningeal lesions that do not meet the measurement requirements for
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16
years of age
- Note: Neurologic deficits in patients with CNS tumors must have been relatively
stable for at least 7 days prior to study enrollment; patients who are unable to
walk because of paralysis, but who are up in a wheelchair, will be considered
ambulatory for the purpose of assessing the performance score
- Patients must have fully recovered from the acute toxic effects of all prior
anti-cancer therapy and must meet the following minimum duration from prior
anti-cancer directed therapy prior to enrollment; if after the required timeframe, the
numerical eligibility criteria are met, e.g. blood count criteria, the patient is
considered to have recovered adequately
- Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
- >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy
(42 days if prior nitrosourea)
- Anti-cancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the
last dose of agent
- Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody,
and toxicity related to prior antibody therapy must be recovered to grade =< 1
- Corticosteroids: If used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
- Hematopoietic growth factors: >= 14 days after the last dose of a long-acting
growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for
growth factors that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which adverse
events are known to occur; the duration of this interval must be discussed with
the study chair and the study-assigned research coordinator
- Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
- Stem cell infusions (with or without total body irradiation [TBI]):
- Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem
cell infusion including donor lymphocyte infusion (DLI) or boost infusion:
>= 84 days after infusion and no evidence of graft versus host disease
(GVHD)
- Autologous stem cell infusion including boost infusion: >= 42 days
- Cellular therapy: >= 42 days after the completion of any type of cellular therapy
(e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
- Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >=
50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
- Note: Radiation may not be delivered to "measurable disease" tumor site(s)
being used to follow response to subprotocol treatment
- Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131iodine [I]-MIBG): >=
42 days after systemically administered radiopharmaceutical therapy
- Patients must not have received prior exposure to olaparib, veliparib, niraparib,
rucaparib, talazoparib or other poly adenosine diphosphate ribose polymerase
inhibitors (PARPi)
- For patients with solid tumors without known bone marrow involvement: peripheral
absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to enrollment)
- For patients with solid tumors without known bone marrow involvement: platelet count
>= 100,000/mm^3 (within 7 days prior to enrollment) (transfusion independent, defined
as not receiving platelet transfusions for at least 7 days prior to enrollment)
- Patients with known bone marrow metastatic disease will be eligible for study provided
they meet the blood counts (may receive platelet or packed red blood cells [pRBC]
transfusions provided they are not known to be refractory to red cell or platelet
transfusions); these patients will not be evaluable for hematologic toxicity
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
ml/min/1.73 m^2 (within 7 days prior to enrollment) or
- A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
- Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for
female
- Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for
female
- Age 6 to < 10 years: maximum serum creatinine 1 mg/dL for male and 1 mg/dL for
female
- Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL for male and 1.2 mg/dL
for female
- Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL for male and 1.4 mg/dL
for female
- Age >= 16 years: maximum serum creatinine 1.7 mg/dL for male and 1.4 mg/dL for
female
- Patients with solid tumors: bilirubin (sum of conjugated + unconjugated) =< 1.5 x
upper limit of normal (ULN) for age (within 7 days prior to enrollment)
- Patients with solid tumors: serum glutamic pyruvic transaminase (SGPT) (alanine
aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment); (for the
purpose of this study, the ULN for SGPT is 45 U/L)
- Patients with solid tumors: serum albumin >= 2 g/dL (within 7 days prior to
enrollment)
- Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (within 7 days prior to
enrollment)
- International normalized ratio (INR) =< 1.5 (within 7 days prior to enrollment)
- Patients must be able to swallow intact tablets
- All patients and/or their parents or legally authorized representatives must sign a
written informed consent; assent, when appropriate, will be obtained according to
institutional guidelines
Exclusion Criteria:
- Pregnant or breast-feeding women will not be entered on this study due to risks of
fetal and teratogenic adverse events as seen in animal/human studies; pregnancy tests
must be obtained in girls who are post-menarchal; women of child-bearing potential and
their partners should agree to use two (2) highly effective forms of contraception
throughout study participation and for at least one (1) month after the last dose of
olaparib; male study participants should avoid fathering a child or donating sperm
during the study and for three (3) months after the last dose of olaparib
- Concomitant medications
- Corticosteroids: patients receiving corticosteroids who have not been on a stable
or decreasing dose of corticosteroid for at least 7 days prior to enrollment are
not eligible; if used to modify immune adverse events related to prior therapy,
>= 14 days must have elapsed since last dose of corticosteroid
- Investigational drugs: patients who are currently receiving another
investigational drug are not eligible
- Anti-cancer agents: patients who are currently receiving other anti-cancer agents
are not eligible
- Anti-GVHD agents post-transplant: patients who are receiving cyclosporine,
tacrolimus or other agents to prevent graft-versus-host disease post bone marrow
transplant are not eligible for this trial
- CYP3A/CYP3A4 agents: patients who are currently receiving drugs that are strong
and moderate inducers or inhibitors of CYP3A or CYP3A4 are not eligible; strong
inducers or inhibitors of CYP3A4 should be avoided from 21 days prior to
enrollment to the end of the study
- Patients who have an uncontrolled infection are not eligible
- Patient who are known to be serologically positive for human immunodeficiency virus
(HIV)
- Patients with known active hepatitis (i.e. hepatitis B or C)
- Patients who have received a prior solid organ transplantation are not eligible
- Patients with symptomatic uncontrolled brain metastases; a scan to confirm the absence
of brain metastases is not required; the patient can receive a stable dose of
corticosteroids before and during the study as long as these were started at least 4
weeks prior to enrollment; patients with spinal cord compression unless considered to
have received definitive treatment for this and evidence of clinically stable disease
for 28 days
- Patients with known symptomatic Fanconi anemia (FA), ataxia-telangiectasia (A-T)
syndrome, Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are not eligible
(asymptomatic carriers are acceptable)
- Major surgery must not have occurred within 2 weeks prior to enrollment and patients
must have recovered from any effects of any major surgery
- Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study are not eligible