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

ConditionsMalignant Ovarian Epithelial TumorPlatinum-Resistant Fallopian Tube CarcinomaPlatinum-Resistant Ovarian CarcinomaPlatinum-Resistant Primary Peritoneal CarcinomaRecurrent Fallopian Tube CarcinomaRecurrent Ovarian CarcinomaRecurrent Primary Peritoneal CarcinomaRefractory Fallopian Tube CarcinomaRefractory Ovarian CarcinomaRefractory Primary Peritoneal Carcinoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18+
SponsorIra Winer

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

  • Akt/ERK Inhibitor ONC201

    Drug

    Given orally (PO)

  • Paclitaxel

    Drug

    Given IV

  • Questionnaire Administration

    Other intervention

    Ancillary studies

Treatment groups

62 Participants
are divided into 1 treatment group
Group A: Treatment - ONC201 & PaclitaxelExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

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.

Time frame
Up to 28 days
2

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

Graded according to NCI CTCAE v5.0.

Time frame
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.

Time frame
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.

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

Secondary outcomes

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.

Time frame
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.

Time frame
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.

Time frame
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.

Time frame
At 6 months

Other outcomes

1

NK cell evaluation

NK cell evaluation by immunohistochemistry (IHC) will be performed. Wilcoxon signed ranks test will be used to compare individuals and groups pre/post treatment. Percentage of NK cells as a component of total lymphocytes over time will be evaluated using repeated measures ANOVA. Additionally, percentage of Granzyme+ and TRAIL+ NK cells will be evaluated comparing day 0 (pre-treatment) and day 4 via paired two sided t-test analysis.

Time frame
Up to 1 year
2

Cytokine profile

Repeated measured ANOVA will be conducted to assess for any changes in each of these molecules/cytokines over 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.

Time frame
Up to 1 year

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Ira Winer

Lead sponsor

Barbara Ann Karmanos Cancer Institute

Sponsor institution

Source ClinicalTrials.gov
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