Selinexor in Treating Patients With Abiraterone Acetate and/or Enzalutamide Refractory Metastatic Castration-Resistant Prostate Cancer

NCT02215161 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: 14552NCI-2014-0193614-13390
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies selinexor in treating patients with prostate cancer that has spread to other parts of the body (metastatic), keeps growing even when the amount of testosterone in the body is reduced to very low levels (castration-resistant), and did not respond to treatment (refractory) with abiraterone acetate and/or enzalutamide. Selinexor may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Castration Levels of Testosterone; Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma in the Soft Tissue; Prostate Carcinoma Metastatic in the Bone; PSA Progression; Stage IV Prostate Adenocarcinoma AJCC v7

Outcome Measures

Primary Outcomes (1)

• Radiographic Progression Free Survival (rPFS)

  Defined as the time from study start until one of the following events occurs: \>= 2 new bone lesions on technetium bone scan; Response Evaluation Criteria in Solid Tumors (RECIST)-defined tumor progression; clinical deterioration requiring a change in prostate cancer therapy, or at clinician discretion; surgery or radiation to treat a prostate cancer related indication; or death from any cause.

  From study start up to 3 years

Secondary Outcomes (9)

• Abiraterone Resistance Status (Primary Versus Acquired)

  At baseline

• Time to PSA Progression

  Time between the first evaluation at which the response criteria are met and the first documentation of PSA progression or death or up to 3 years

• Incidence of Non-serious Adverse Events

  Up to 3 years after treatment start

• Comparison of Leukocyte Exportin 1 (XPO-1) and Macrophage Inhibitory Cytokine-1 (MIC-1) Gene Expression Levels Pre- and Post-Selinexor Treatment

  On days 1 and 15 of course 1 and on day 1 of courses 2 and 3

• PSA Decline of ≥50% at 12 Weeks Post Therapy Initiation

  At 12 weeks post therapy initiation

Study Arms (1)

Treatment (selinexor)

EXPERIMENTAL

Patients receive selinexor PO on days 1 and 3 of weeks 1-3. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Selinexor

Interventions

Selinexor DRUG

Given PO

Also known as: CRM1 Nuclear Export Inhibitor KPT-330, KPT-330, Selective Inhibitor of Nuclear Export KPT-330, SINE KPT-330

Treatment (selinexor)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed adenocarcinoma of the prostate
• Patients must have castrate levels of testosterone (\< 50 ng/dL) on gonadotropin-releasing hormone (GnRH) analogues or have had prior orchiectomy; GnRH analogues must be continued while on study
• Tumor tissue submitted for molecular and genetic analysis through the companion Stand-up 2 Cancer (SU2C) radiologically guided biopsy of abiraterone and/or enzalutamide refractory mCRPC protocol
• Patients who consent to participate in the companion biopsy protocol and are subsequently determined to be ineligible for biopsy are eligible to participate in the current protocol
• Progressive disease as demonstrated by a rising PSA (at least two determinations) prior to study entry, and/or radiographic evidence of tumor progression in soft tissue according to modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria or identification of new lesions by bone scan (i.e., \>= 2 new lesions)
• Primary resistance or acquired resistance (i.e., acquired resistance will be defined as disease progression following a period of response defined as \>= 50% decline in PSA within 12 weeks of starting therapy and not otherwise meeting criteria for primary resistance) to any of the following agents/combinations of therapy:
• Abiraterone acetate; primary resistance to abiraterone will be defined as:
• No PSA decline
• PSA decline less than 50% after 12 weeks of abiraterone therapy
• PSA progression within 12 weeks of abiraterone acetate (AA) treatment (by Prostate Cancer Working Group-2 \[PCWG2\] criteria), after initial response to therapy
• Objective progression, by RECIST criteria for soft tissue lesions and by modified PCWG2 criteria for bone lesions within 12 weeks of starting abiraterone treatment
• Unequivocal clinical progression (per the treating provider's discretion) within 12 weeks of starting abiraterone treatment
• Enzalutamide; primary resistance to enzalutamide will be defined as:
• No PSA decline
• PSA decline less than 50% after 12 weeks of enzalutamide therapy

You may not qualify if:

• Untreated brain metastases; brain metastases =\< 1 cm and not associated with any focal neurologic deficits are allowed
• Prior docetaxel or other chemotherapy for mCRPC; patients who have received docetaxel for metastatic hormone-sensitive prostate cancer are eligible
• Active or symptomatic viral hepatitis or chronic liver disease
• Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) class II-IV heart disease or known cardiac ejection fraction measurement of \< 50 % at baseline
• Patients with significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea or other gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents
• Pure small cell carcinoma of the prostate or any mixed histology cancer of the prostate (eg: neuroendocrine) that contains \< 50% adenocarcinoma, as observed on biopsy obtained at the time of diagnosis or on any subsequent biopsies
• Any ?currently active? second malignancy, other than non-melanoma skin cancer; patients are not considered to have a "currently active? malignancy, if they have completed therapy and are considered by their physician to be at least less than 30% risk of relapse over next year
• Any condition, which in the opinion of the investigator, would preclude participation in this trial
• Active psychiatric illnesses/social situations that would limit compliance with protocol requirements
• Patients in whom urgent treatment with docetaxel is indicated, per clinician discretion; this includes, but is not limited to patients with symptomatic visceral metastatic disease
• Uncontrolled infection or concomitant medical illness that is not adequately controlled with current medical management, as determined per clinician discretion
• Active bleeding disorders or evidence of evidence of chronic or acute disseminated intravascular coagulation (DIC)
• Severely compromised immunological state, including known human immunodeficiency virus (HIV)
• Any acute toxicities due to prior anti-cancer treatments and/or radiotherapy that have not resolved to a National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade of =\< 1 (except alopecia)
• Prior radiation therapy completed \< 3 weeks or single fraction of palliative radiotherapy \< 14 days prior to first dose of KPT-330 (selinexor)

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94115, United States

Location

Related Publications (1)

• Wei XX, Siegel AP, Aggarwal R, Lin AM, Friedlander TW, Fong L, Kim W, Louttit M, Chang E, Zhang L, Ryan CJ. A Phase II Trial of Selinexor, an Oral Selective Inhibitor of Nuclear Export Compound, in Abiraterone- and/or Enzalutamide-Refractory Metastatic Castration-Resistant Prostate Cancer. Oncologist. 2018 Jun;23(6):656-e64. doi: 10.1634/theoncologist.2017-0624. Epub 2018 Feb 27.

  PMID: 29487219 DERIVED

MeSH Terms

Interventions

selinexor

Limitations and Caveats

The study was terminated due to unacceptable toxicity.

Results Point of Contact

• Title: Charles Ryan, MD
• Organization: University of California, San Francisco

clinicaltrials@ucsf.edu

877-827-3222

Study Officials

• Charles Ryan, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: July 30, 2014
• First Posted: August 13, 2014
• Study Start: September 2, 2014
• Primary Completion: February 15, 2017
• Study Completion: April 2, 2018
• Last Updated: June 26, 2018
• Results First Posted: June 26, 2018

Record last verified: 2018-05

Locations

US (1)