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

  • STATUS
    Recruiting
  • End date
    Jan 31, 2022
  • participants needed
    62
  • sponsor
    Ira Winer
Updated on 11 July 2021
Investigator
Ira Winer
Primary Contact
Barbara Ann Karmanos Cancer Institute (2.6 mi away) Contact

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.

Description

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of the combination of Akt/ERK inhibitor ONC 201 (ONC201) and paclitaxel in patients with platinum refractory or resistant epithelial ovarian, fallopian tube or primary peritoneal cancer. (Part 1) II. To evaluate the objective response rate (ORR) of ONC201 in combination with paclitaxel in patients with platinum refractory or resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. (Part 2) III. To evaluate progression free survival (PFS) of ONC201 in combination with weekly paclitaxel in patients with platinum refractory or resistant epithelial ovarian, fallopian tube or primary peritoneal cancer. (Part 2)

SECONDARY OBJECTIVES:

I. To evaluate the durability/duration of response (DOR) of ONC201 in combination with paclitaxel.

II. To evaluate the safety and patient reported tolerability of ONC201 in combination with paclitaxel. (Part 2) III. To evaluate the disease control rate (DCR) of ONC201 in combination with paclitaxel.

IV. To evaluate the cancer antigen-125 (CA-125) and/or human epididymis factor 4 (HE-4) response of ONC201 in combination with paclitaxel in those patients with one or both of these tumor markers upregulated.

V. To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of ONC201 in combination with paclitaxel.

VI. To obtain preliminary estimates of overall survival (OS) of ONC201 in combination with weekly paclitaxel.

EXPLORATORY OBJECTIVES:

I. To evaluate the immune response (specifically natural killer [NK] cell and cytokine profile) of ONC201 in combination with paclitaxel in patients with platinum refractory or resistant epithelial ovarian, fallopian tube or primary peritoneal cancer.

OUTLINE

Patients receive ONC201 orally (PO) on days 1, 8, and 15, and paclitaxel intravenously (IV) over 1 hour on days 2, 9, and 16. Cycles repeat every 28 days in the absence disease progression or unacceptable toxicity. If paclitaxel must be stopped for any reason, patients may continue on ONC201 alone.

After completion of study treatment, patients are followed up for 1 year.

Details
Condition Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma, Recurrent Ovarian Cancer, Refractory Fallopian Tube Carcinoma, Refractory Ovarian Carcinoma, Refractory Primary Peritoneal Carcinoma, Malignant Ovarian Epithelial Tumor, Platinum-Resistant Fallopian Tube Carcinoma, Platinum-Resistant Ovarian Carcinoma, Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Resistant Fallopian Tube Carcinoma, Platinum-Resistant Ovarian Carcinoma, Platinum-Resistant Primary Peritoneal Carcinoma
Treatment questionnaire administration, Paclitaxel, Akt/ERK Inhibitor ONC201
Clinical Study IdentifierNCT04055649
SponsorIra Winer
Last Modified on11 July 2021

Eligibility

Yes No Not Sure

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)
Bone marrow function: Absolute neutrophil count (ANC) 1,500/L. Platelets
000/L and hemoglobin > 8.0 gm/dL, transfusion allowed up to 1 week prior
to maintain Hgb >8\
\. Renal function: Calculated creatinine clearance (CrCl) 35 mL/min/1.73 mm2
\. 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
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