Overview

ONC201 Plus Weekly Paclitaxel in Patients With Platinum Refractory or Resistant Ovarian Cancer

Status:
Recruiting
Trial end date:
2022-01-31
Target enrollment:
0
Participant gender:
Female
Summary
This phase II trial studies the side effects of ONC201 and paclitaxel and how well they work in treating patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer that has come back (recurrent), or that does not respond to treatment (refractory). ONC201 is the first in its class of drugs that antagonize some specific cell receptors on cancer cells, leading to their destruction. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ONC201 and paclitaxel may work better in treating patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer compared to paclitaxel alone.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Ira Winer
Treatments:
Albumin-Bound Paclitaxel
Paclitaxel
TIC10 compound
Criteria
Inclusion Criteria:

- Histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal
cancer.

- Progressed within 6 months of completing at least 1 cycle of last platinum containing
regimen. Patients with refractory disease (progression during platinum-containing
therapy) are eligible. This includes both adjuvant therapy and in the recurrent
setting.

- No more than 4 prior treatment regimens defined as investigational, chemotherapy,
hormonal, biologic, or targeted therapy in the platinum resistant setting and total of
7 prior regimens in all settings will be allowed. Prior maintenance therapy with
biologic or targeted agent does NOT count as a treatment regimen (e.g. Maintenance
bevacizumab, Parpi, or immunotherapy).

- At least one measurable lesion according to RECIST v1.1.

- For the eight patients enrolled for PK/PD. Availability of tissue from carcinoma. For
most patients this will be archival tissue. If there is no archival tissue available,
biopsy of lesion MUST be performed prior to initiation of therapy. Lesions must be
available for biopsy as well in these patients.

- Any prior palliative radiation therapy must be completed at least 7 days prior to
start of study treatment and patients must have recovered from any acute adverse
effects prior to start of study treatment.

- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-1.

- Female patients who are not of childbearing potential and fertile female patients of
childbearing potential who agree to use adequate contraceptive measures from 2 weeks
prior to the study and until 1 month after study treatment discontinuation, who are
not breastfeeding, and who have a negative serum or urine pregnancy test within 3 days
prior to start of study treatment.

- Patients must have adequate (at baseline):

1. Bone marrow function: Absolute neutrophil count (ANC) ≥1,500/µL. Platelets

≥100,000/µL and hemoglobin > 8.0 gm/dL, transfusion allowed up to 1 week prior to
maintain Hgb >8.

2. Renal function: Calculated creatinine clearance (CrCl) ≥35 mL/min/1.73 mm2

3. Hepatic function: Bilirubin less than or equal to 1.5 x ULN; alkaline phosphatase
(AP), aspartate transaminase (AST) and alanine transaminase (ALT) less than or
equal to 3 x ULN. AP, AST and ALT less than or equal to 5 x ULN is acceptable if
patient has known hepatic metastasis

Exclusion Criteria:

- Use of a study drug (approved or investigational drug therapy) ≤21 days or 5
half-lives (whichever is shorter) prior to the first dose of study treatment. For
study drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between
termination of the study drug and administration of current study treatment is
required.

- Major surgical procedures ≤21 days of beginning study treatment, or minor surgical
procedures ≤7 days. No waiting required following port-a-cath placement, ureteral
stent placement, percutaneous nephrostomy tube placement.

- No other (chemotherapy, immunotherapy, hormonal anti-cancer therapy, radiotherapy
[except for palliative local radiotherapy]), biological therapy or other novel agent
is to be permitted while the patient is receiving study medications

- Grade >1 toxicity from prior therapy (except alopecia or anorexia or above hematologic
criteria) unless controlled by medications.

- Inability to swallow oral medication. Note: Patient may not have a percutaneous
endoscopic gastrostomy (PEG) tube or be receiving total parenteral nutrition (TPN) on
this trial.

- Known malignant central nervous system disease other than neurologically stable,
treated brain metastases - defined as metastasis having no evidence of progression
after treatment for at least 4 weeks (including brain radiotherapy). Must be off any
systemic corticosteroids for the treatment of brain metastases for at least 14 days
prior to enrollment.

- Patient has had prescription or non-prescription drugs or other products (i.e.
grapefruit juice) known to be moderate to strong inhibitors or inducers of CYP3A4,
which cannot be discontinued 1 week prior to Day 1 of dosing and withheld throughout
the study until 1 weeks after the last dose of study drug.

- Any known hypersensitivity or contraindication to the components of study treatment

- Pregnant or lactating

- Serious active infection at the time of enrollment, or another serious underlying
medical condition at discretion of the enrolling physician that would impair the
ability of the patient to receive study treatment. HIV or other immunodeficiency
disease that is well controlled and that does not impact baseline lab values (i.e.
outside of above noted parameters for inclusion) are NOT considered exclusion
criteria.

- Presence of other active cancers other than ovarian cancer except those that do not
require active therapy (i.e. on surveillance) and known non-invasive cancers and in
situ cancers (e.g. non-melanoma skin cancers).

- Psychological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol.