This phase II trial tests whether pegylated SN-38 conjugate PLX038 (PLX038) works to shrink tumors in patients with ovarian, primary peritoneal, and fallopian tube cancers that has spread from where it first started (primary site) to other places in the body (metastatic). PLX038 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Age >= 18 years NOTE: Because no dosing or adverse event data are currently available on the use of PLX038 in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
Histological confirmed high grade serous ovarian cancer consistent with ovarian, fallopian tube, or primary peritoneal carcinoma (NOTE: Any of these diseases are referred to in this protocol as "ovarian cancer")
Recurrent high grade serous ovarian cancer that was initially platinum sensitive (i.e., had at least one platinum-free interval of at least 6 months before progression) is now platinum resistant
No more than one prior line of therapy for platinum resistant disease. NOTE: Prior poly adenosine diphosphate-ribose polymerase (PARP) inhibitor therapy is allowed
Pregnant persons
Nursing persons
Persons of childbearing potential who are unwilling to employ adequate contraception
Histology other than high grade serous carcinoma
Single group
Biopsy
Procedure/SurgeryUndergo biopsy
Pegylated SN-38 Conjugate PLX038
DrugGiven IV
Computed Tomography
Procedure/SurgeryUndergo CT
Biospecimen Collection
Procedure/SurgeryUndergo blood and stool sample collection
Proportion of confirmed tumor responses
A confirmed tumor response is defined to be either a complete response or partial response noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. Confirmed tumor response will be evaluated using the first 6 cycles of treatment. All patients meeting the eligibility criteria who have signed a consent form, have begun treatment, and who have had at least one post-baseline tumor assessment will be evaluable for response. Patients not having met the criteria of having one post-baseline tumor assessment will be considered evaluable if they have discontinued the study due to disease progression.
Progression-free survival (PFS)
PFS will be estimated using the Kaplan-Meier method.
Overall survival (OS)
OS will be estimated using the Kaplan-Meier method.
Incidence of adverse event rates
The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The frequency and percentage of Grade 3+ adverse events will be reported.
TOP1-deoxyribonucleic acid covalent complexes (TOP1cc)
TOP1cc will be assessed on archival tissue and from pre-treatment and day 8 biopsies. The primary analysis is the relationship between induction of TOP1cc and individual responses. TOP1cc will be summarized for each sample as the percent of tumor cells with \> 8 nucleoplasmic TOP1ccs. The change in TOP1cc from pre-treatment and day 8 samples (DTOP1cc) will be compared between responders and non-responders via two-sample t-tests. TOP1cc will be assessed in circulating tumor cells (CTC) from samples drawn pretreatment, cycle 1 day 2 and cycle 1 day 8. Presence of TOPcc in CTC will be examined graphically in an exploratory fashion. If feasible, comparisons of quantification between TOPcc in tissue versus CTC will be performed using Spearman correlation and scatter plots and association between TOPcc in CTC and response will be assessed as in tissue samples.
Homologous recombination (HR) status
(HR) status (deficient versus proficient) will be assessed via staining for RAD51 foci on pretreatment and day 8 tumor biopsies. HR status will be compared to tumor response via chi-squared tests.
Protein expression
Protein expression of ABCG2 will be measured via immunohistochemistry (IHC) on archival and pretreatment biopsies. H-scores will be used to score IHC staining, and H-scores will be compared between responders and non-responders using two-sample t-tests as indicated for TOP1cc.
Correlative analyses
Exploratory analyses examining the association between correlative endpoints and other clinical endpoints (PFS and OS) may also be performed using Cox proportional hazards models and Kaplan Meier curves.
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Mayo Clinic
Lead sponsor
National Cancer Institute (NCI)
Collaborator
