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

NCT04055649 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2018-126
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (4)

• Incidence of treatment related adverse events (AEs) (Part 1)

  Graded according to National Cancer Institute (NCI) Common Terminology Criteria in Adverse Events (CTCAE) version (v)5.0.

  Up to 28 days

• Incidence of dose limiting toxicities (DLT's) (Part 1)

  Graded according to NCI CTCAE v5.0.

  Up to 28 days

• Objective response rate (ORR) (Part 2)

  Defined as the proportion of patients achieving a complete (CR) or partial tumor response (PR) by computed tomography (CT) evaluation according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Will be calculated as the proportion of patients achieving a complete or partial tumor response according to RECIST v1.1 criteria and its associated 1-sided 92% confidence interval (CI) will be also estimated using Pearson-Klopper's exact method.

  Up to 1 year

• Progression free survival (PFS) (Part 2)

  Will be summarized using Kaplan-Meier (KM) curves and their median and confidence intervals (CI's) will be further estimated.

  From study treatment initiation to objective tumor progression or death, assessed up to 1 year

Secondary Outcomes (9)

• Duration of response (DOR)

  From first documented tumor response until the date of documented progression or death from any cause, assessed up to 1 year

• Incidence of treatment related AEs

  Up to 1 year

• Incidence of patient reported symptoms

  Up to 1 year

• Disease clinical response (DCR)

  At 6 months

• CA-125 response rate

  Up to 1 year

Other Outcomes (2)

• NK cell evaluation

  Up to 1 year

• Cytokine profile

  Up to 1 year

Study Arms (1)

Treatment - ONC201 & Paclitaxel

EXPERIMENTAL

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.

Drug: Akt/ERK Inhibitor ONC201; Drug: Paclitaxel; Other: Questionnaire Administration

Interventions

Akt/ERK Inhibitor ONC201 DRUG

Given orally (PO)

Also known as: ONC201, TIC10

Treatment - ONC201 & Paclitaxel

Paclitaxel DRUG

Given IV

Also known as: Ester, Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat, Alpha, Beta

Treatment - ONC201 & Paclitaxel

Questionnaire Administration OTHER

Ancillary studies

Treatment - ONC201 & Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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/µL. Platelets
• ≥100,000/µL 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ira Winer: lead

Study Sites (2)

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Karmanos Cancer Institute at McLaren Flint

Flint, Michigan, 48532, United States

RECRUITING

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

TIC10 compound; Paclitaxel; Esters; Taxes

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Carboxylic Acids; Economics; Health Care Economics and Organizations

Study Officials

• Ira Winer, M.D.

  Barbara Ann Karmanos Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ira Winer, M.D.

CONTACT

(313) 576-9435; iwiner@med.wayne.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 12, 2019
• First Posted: August 14, 2019
• Study Start: January 21, 2020
• Primary Completion (Estimated): May 28, 2026
• Study Completion (Estimated): May 28, 2027
• Last Updated: June 18, 2025

Record last verified: 2025-06

Locations

US (2)