| Eligibility |
Inclusion Criteria:
- Patients with recurrent ovarian cancer. Ovarian cancer = fallopian tube cancer,
ovarian cancer, primary peritoneal cancer. The following histology types are eligible:
- High grade serous
- Endometrioid, grade 3
- Any histology with BRCA1 and/or BRCA2 deleterious mutation (germline or somatic)
- Histologic confirmation of the original primary tumor is required via the
pathology report (upload of report required)
- Confirmation of BRCA1 and BRCA2 germline status is required for all entered
patients (upload of report[s] required)
- Tumor/somatic genomic testing can be provided or entered as not done (upload
of report[s] required)
- Homologous recombination deficiency (HRD) testing can be provided or entered
as not done (upload of report[s] required)
- Genetic/genomic testing results and HRD testing results, initially entered
as not done, should be uploaded if they become available anytime during
conduct of the study
- Participants must have progressed by imaging while receiving PARP inhibitor therapy
(irrespective of whether PARP inhibitor therapy was given as maintenance therapy or as
primary recurrence therapy); rising CA125 only is not considered as evidence of
progression
- Platinum-resistant disease, defined as progression within < 6 months from completion
of platinum-based therapy, and inclusive of platinum refractory disease. The date
should be calculated from the last administered dose of platinum therapy
- Unlimited lines of cytotoxic therapy allowed in the platinum-sensitive setting; =< 2
lines of cytotoxic therapy allowed in the platinum-resistant setting
- Hormonal therapy (e.g., tamoxifen, aromatase inhibitors) will not count as a
previous line of therapy
- Prior use of bevacizumab in the upfront or recurrent setting is required
- Participants must have evaluable disease - defined as RECIST 1.1 measurable disease OR
non-measurable disease (defined as solid and/or cystic abnormalities on radiographic
imaging that do not meet RECIST 1.1 definitions for target lesions OR ascites and/or
pleural effusion that has been pathologically demonstrated to be disease-related in
the setting of a CA125 > 2 x upper limit of normal [ULN])
- Age >= 18
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or 2
- Absolute neutrophil count (ANC) >= 1,500/mcl (within 14 days prior to registration)
- Hemoglobin >= 10 g/dL (within 14 days prior to registration)
- Platelets >= 100,000/mcL (within 14 days prior to registration)
- Creatinine clearance (CrCL) >= 51 mL/min (estimated using Cockcroft-Gault equation)
(within 14 days prior to registration)
- Total serum bilirubin level =< 1.5 x ULN (patients with known Gilbert's disease who
have bilirubin level =< 3 x ULN may be enrolled) (within 14 days prior to
registration)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (within
14 days prior to registration)
- Lipase =< 1.5 x ULN within 14 days of registration
- International normalized ratio (INR) =< 1.5 x ULN (or an in-range INR, usually between
2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial
thromboplastin time (PTT) =< 1.5 times the upper limit of normal within 14 days of
registration
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional classification. To be
eligible for this trial, patients should be class 2B or better
- Patients who are therapeutically treated with an agent such as warfarin or heparin
will be allowed to participate provided that their medication dose and INR/PTT is
stable. Oral anticoagulants are allowed provided there are no interactions
- The effects of copanlisib and olaparib on the developing human fetus are unknown. For
this reason and because maternal toxicity, developmental toxicity and teratogenic
effects have been observed in nonclinical studies and PI3K inhibitors agents as well
as other therapeutic agents used in this trial are known to be teratogenic, women of
child-bearing potential must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence) prior to study entry and for the duration of
study participation, and for 1 month after the last dose of copanlisib and/or
olaparib. Should a woman become pregnant or suspect she is pregnant while she is
participating in this study, she should inform her treating physician immediately
- Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months of registration are eligible for
this trial
- Patients with evidence of chronic hepatitis B virus (HBV) infection must have an
undetectable HBV viral load on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
- Patients with treated brain metastases are eligible if follow-up brain imaging after
central nervous system (CNS)-directed therapy shows no evidence of progression and
must be off steroids and stable at least one month
- The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry and, for patients treated in the United States
(U.S.), authorization permitting release of personal health information
Exclusion Criteria:
- Prior therapy:
- No chemotherapy or radiotherapy within 4 weeks of registration
- No hormonal therapy within 2 weeks of registration. Patients receiving raloxifene
for bone health as per Food and Drug Administration (FDA) indication may remain
on raloxifene absent other drug interactions
- No investigational agents within 4 weeks of registration
- No prior PI3K-AKT-mTOR pathway inhibitor therapy
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to olaparib, copanlisib, or other agents used in this study
- Copanlisib and olaparib are primarily metabolized by CYP3A4. Therefore, the
concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole,
clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and strong inducers
of CYP3A4 (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort)
are not permitted from 14 days prior to registration until the end of the study
- Systemic corticosteroid therapy at a daily dose higher than 15 mg prednisone or
equivalent is not permitted while on study. Patients may be using topical or inhaled
corticosteroids
- Use of concomitant herbal medications/preparations (except for vitamins),
alternative/complimentary medications, immunosuppressive therapy, or other prohibited
medications
- Patients with uncontrolled type I or II diabetes mellitus; uncontrolled diabetes is
defined as glycosylated hemoglobin (HbAlc) > 8.5%
- Patients with arterial or venous thrombotic or embolic events such as cerebrovascular
accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary
embolism within 3 months before registration
- Gastrointestinal conditions that would preclude consumption (swallowing), retention,
and/or absorption of oral medications
- Patients with drainage gastrostomy tube are not allowed
- Patients with dependency on IV hydration or total parenteral nutrition (TPN) are not
allowed
- Patients with uncontrolled intercurrent illness, including but not limited to:
- Persistent grade >= 2 adverse events due to prior anti-cancer therapy with the
exception of alopecia, hypothyroidism requiring medication, vitiligo, and the
laboratory values defined in the inclusion criteria.
- Known psychiatric illness/social situations that would limit compliance with
study requirements.
- History of or current autoimmune disease
- Non-healing wound, ulcer, or bone fracture
- Active, clinically serious infections > grade 2 (CTCAE v5.0)
- Women who are pregnant or unwilling to discontinue nursing
- Patients who have a history of non-infectious pneumonitis/interstitial lung disease
(ILD) that required steroids, or current non-infectious pneumonitis/ILD
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