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Malignant Ovarian Epithelial TumorPhase 2NCT04055649

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

A Phase 2 study testing Akt/ERK Inhibitor ONC201, Paclitaxel and Questionnaire Administration in people with Malignant Ovarian Epithelial Tumor and Platinum-Resistant Fallopian Tube Carcinoma, run by Ira Winer at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Akt/ERK Inhibitor ONC201, Paclitaxel and Questionnaire Administration
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
2 sitesUnited States
Study dates
21 Jan 2020to 28 May 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Ira Winer, M.D. contact

(313) 576-9435

iwiner@med.wayne.edu

United States2 sites, 2 recruiting

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

    Clinical Trials Office, (800) 527-6266

    Robert Morris, M.D.

    Recruiting

  • Karmanos Cancer Institute at McLaren Flint

    Flint, Michigan, 48532

    John J Wallbillich, M.D., jwallbil@med.wayne.edu

    Recruiting

Other trials in United States

About this study

Official title: Phase II Study of ONC201 Plus Weekly Paclitaxel in Patients With Platinum-Resistant Refractory or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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:

  1. 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.

Being tested
Akt/ERK Inhibitor ONC201, Paclitaxel, Questionnaire Administration
Medical subject headings
Fallopian Tube Neoplasms, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Akt/ERK Inhibitor ONC201Drug

    Also called ONC201, TIC10

    Given orally (PO)

  • PaclitaxelDrug

    Also called Ester, Anzatax, Asotax, Bristaxol

    Given IV

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT04055649
Study groupRoleWhat they receive
Treatment - ONC201 & PaclitaxelExperimentalPatients 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.
Receives: Drug: Akt/ERK Inhibitor ONC201; Drug: Paclitaxel; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 28 days

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

    Graded according to NCI CTCAE v5.0.

    Measured: Up to 28 days

  3. 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.

    Measured: Up to 1 year

  4. 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.

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

Secondary outcomes (9)

  1. Duration of response (DOR)

    The distributions of additional time-to-event endpoints will be summarized using KM curves and their median and CI's will be further estimated using KM estimates.

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

  2. Incidence of treatment related AEs

    Treatment emergent AEs and serious adverse events (SAEs) will be summarized by count and percentage per CTCAE v5.0.

    Measured: Up to 1 year

  3. Incidence of patient reported symptoms

    Will be summarized by count and percentage from the Functional Assessment of Cancer Therapy (FACT)-Taxane questionnaire. Repeated measured analysis of variance (ANOVA) will be conducted to assess for any changes in these symptoms by time. If a significant association with time is identified, pairwise comparisons between various time-points will be assessed using paired t-tests with a Tukey adjustment for multiple comparisons.

    Measured: Up to 1 year

  4. Disease clinical response (DCR)

    Defined as the proportion of patients achieving a complete response (CR), partial response (PR), or stable disease (SD) according to RECIST v1.1 criteria.

    Measured: At 6 months

  5. CA-125 response rate

    Defined as the proportion of patients achieving a 50% reduction in CA-125 levels from baseline, if baseline level is >= 2 x the upper limit of normal (ULN) within 2 weeks prior to starting treatment. Differences in these markers by response will be assessed by Fisher's exact tests, and difference in these markers over time will be assessed using McNemar's tests.

    Measured: Up to 1 year

  6. HE-4 response rate

    Defined as proportion of patients achieving a 50% reduction in HE-4 levels from baseline over time, if baseline level is >= 2 x ULN within 2 weeks prior to starting treatment, respectively. Differences in these markers by response will be assessed by Fisher's exact tests, and difference in these markers over time will be assessed using McNemar's tests.

    Measured: Up to 1 year

  7. Plasma concentrations of ONC201

    Examined to assess drug interactions with paclitaxel and characterize the pharmacokinetics (PK). PK parameters will be estimated using non-compartment or compartment models and summarized in mean and CIs under the assumption of log-normal distribution.

    Measured: Up to 1 year

  8. Pharmacodynamic studies

    As a biomarker of apoptosis, the serum cCK18 (M30 assay) and CK18 (M65 assay) will be used to quantify serum caspase-cleaved and total cytokeratin 18 levels. Prolactin levels will be assayed from the collected serum specimens. Repeated measured ANOVA will be conducted to assess for any changes in apoptosis and prolactin by time. If a significant association with time is identified, pairwise comparisons between various time-points will be assessed using paired t-tests with a Tukey adjustment for multiple comparisons. Tissue based biomarkers will be evaluated based on archival (pretreatment) and on-study biopsy tissue and compared via pre/post treatment H-score both within each individual patient and among the group of patients. Wilcoxon signed rank test will be used for pre/post comparisons.

    Measured: Up to 1 year

  9. Overall survival

    The distributions of additional time-to-event endpoints will be summarized using KM curves and their median and CI's will be further estimated using KM estimates.

    Measured: From study treatment initiation to death, assessed up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2019
  2. Study start21 Jan 2020
  3. Primary completion28 May 2027 (estimated)
  4. Study completion28 May 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
62 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04055649
Sponsor's protocol ID
2018-126
Status last verified
Jun 2026
First submitted
12 Aug 2019
Last updated
17 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Akt/ERK Inhibitor ONC201, Paclitaxel and Questionnaire Administration in people with Malignant Ovarian Epithelial Tumor and Platinum-Resistant Fallopian Tube Carcinoma, run by Ira Winer at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ira Winer, M.D. ((313) 576-9435, iwiner@med.wayne.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of treatment related adverse events (AEs) (Part 1) (time frame: Up to 28 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04055649.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2026.

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