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

NCT ID: NCT04055649

Last Updated: 2025-06-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-21
• Study Completion Date: 2027-05-28

Brief 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.

Detailed 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.

Conditions

Malignant Ovarian Epithelial Tumor; Platinum-Resistant Fallopian Tube Carcinoma; Platinum-Resistant Ovarian Carcinoma; Platinum-Resistant Primary Peritoneal Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Refractory Fallopian Tube Carcinoma; Refractory Ovarian Carcinoma; Refractory Primary Peritoneal Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment - ONC201 & Paclitaxel

Patients receive ONC201 PO on days 1, 8, 15, and 22 and paclitaxel 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.

Group Type: EXPERIMENTAL

Akt/ERK Inhibitor ONC201

Intervention Type: DRUG

Given orally (PO)

Paclitaxel

Intervention Type: DRUG

Given IV

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Interventions

Akt/ERK Inhibitor ONC201

Given orally (PO)

Intervention Type: DRUG

Paclitaxel

Given IV

Intervention Type: DRUG

Questionnaire Administration

Ancillary studies

Intervention Type: OTHER

Other Intervention Names

ONC201; TIC10; Ester; Anzatax; Asotax; Bristaxol; Praxel; Taxol; Taxol Konzentrat; Alpha; Beta

Eligibility 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
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Ira Winer

OTHER

Sponsor Role: lead

Responsible Party

Ira Winer

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ira Winer, M.D.

Role: PRINCIPAL_INVESTIGATOR

Barbara Ann Karmanos Institute

Locations

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status: RECRUITING

Karmanos Cancer Institute at McLaren Flint

Flint, Michigan, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ira Winer, M.D.

Role: CONTACT

iwiner@med.wayne.edu

(313) 576-9435

Facility Contacts

Clinical Trials Office

Role: primary

(800) 527-6266

John J Wallbillich, M.D.

Role: primary

jwallbil@med.wayne.edu

Other Identifiers

2018-126

Identifier Type: -

Identifier Source: org_study_id