SHIP (Selinexor in Hormone Insensitive Prostate Cancer)
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Selinexor
Intervention description: Comparison of different dosages and dosing schedules of drug.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: castrate-resistant prostate cancer; prostate cancer; Karyopharm; KPT-330; selinexor

Summary:

      This is an open-label, Phase 2 clinical study of the oral Selective Inhibitor of Nuclear
      Export (SINE) selinexor (KPT-330) in patients with metastatic castration-resistant prostate
      cancer (mCRPC).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically proven adenocarcinoma of the prostate with evidence for skeletal
             metastases on bone scan and/or CT scan.

          -  Must have received at least one agent known to impact survival (abiraterone,
             enzalutamide, etc.).

          -  Eastern Cooperative Oncology Group (ECOG) less than or equal to (≤ 2) or a Karnofsky
             Performance Status (KPS) ≥ 60%.

          -  Serum testosterone levels less than (<) 50 ng/ml.

          -  Ongoing gonadal androgen deprivation therapy with luteinising hormone-releasing
             hormone (LHRH) analogues or orchiectomy. Participants, who have not had an
             orchiectomy, must be maintained on standard dosing of LHRH analogue therapy at
             appropriate frequency for the duration of the study.

          -  Progression of disease despite androgen ablation shown by objective, documented
             evidence of disease progression (excluding prostate-specific antigen [PSA]), defined
             as one or both of the following:

               1. Soft tissue disease progression defined by Response Evaluation Criteria in Solid
                  Tumors (RECIST) version 1.1

               2. Bone disease progression defined by modified Prostate Cancer Clinical Trials
                  Working Group 2 (PCWG2) with two or more new lesions or bone scan

          -  Discontinuation of all glucocorticoids prescribed to specifically treat prostate
             cancer (e.g., as a secondary hormonal manipulation) greater than (>) 4 weeks prior to
             receiving first dose of study drug. Glucocorticoids prescribed for a chronic
             non-cancer-related illness (e.g., asthma or chronic obstructive pulmonary disease
             [COPD]) that is well controlled with medical management are permissible to an
             equivalent of ≤ 10 milligrams (mg) prednisone daily.

          -  Laboratory requirements:

               1. White blood cell (WBC) count > 3,000/microliter (μL)

               2. Absolute neutrophil count (ANC) > 1,500/μL

               3. Hemoglobin ≥8.0 gram per deciliter (g/dL)

               4. Platelet count ≥150,000/μL

               5. Serum albumin ≥3.0 g/dL

               6. Calculated or measured creatinine clearance > 30 milliliter per minute (mL/min)

          -  A biopsy documenting prostate cancer in a target lesion (e.g., lymph node, bone
             lesion, or soft tissue lesion) within 3 months prior to study entry.

          -  No evidence of chronic or acute disseminated intravascular coagulation or bleeding
             tendency.

          -  Participant must be willing and able to comply with protocol requirements. All
             participants must sign an informed consent indicating that they are aware of the
             investigational nature of this study.

          -  Participant must be willing and able to sign an authorization for the release of their
             protected health information for study purposes.

        Exclusion Criteria:

          -  Histologic variants other than adenocarcinoma in the primary tumor.

          -  Participants who require or may be expected to require urgent treatment with docetaxel
             during the study (e.g., participants with visceral metastases).

          -  Abnormal hepatic function:

               1. Bilirubin > 2 times the upper limit of normal (2 x ULN) (except participants with
                  Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must not have a
                  total bilirubin of > 3 x ULN)

               2. Aspartate transaminase (AST) and alanine transaminase (ALT) > 2.5 x ULN (except
                  participants with known liver involvement of their mCRPC who must not have an AST
                  and ALT > 5 x ULN)

          -  Therapy with other hormonal therapy, including any herbal product known to decrease
             PSA levels (e.g., Saw Palmetto and PC-SPES) within 4 weeks prior to receiving first
             dose of study drug.

          -  Therapy with samarium-153, strontium-89, or radium-223 within 8 weeks prior to first
             dose of study drug.

          -  Uncontrolled infection or concomitant illness that is not controlled with medical
             management.

          -  Prior external beam radiation therapy completed < 3 weeks or single fraction of
             palliative radiotherapy within 14 days prior to first dose of study drug.

          -  Any "currently active" second malignancy, other than non-melanoma skin cancer.
             Participants 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 3 months.

          -  Active psychiatric illnesses/social situations that would limit compliance with
             protocol requirements.

          -  Active or uncontrolled autoimmune disease that may require corticosteroid therapy
             during study.

          -  Severely compromised immunological state, including known human immunodeficiency virus
             (HIV).

          -  Known acute or chronic hepatitis B or C.

          -  Chemotherapy and other investigational therapies (targeted or immunotherapy) will
             require a 3-week washout period before treatment initiation.

          -  Initiation of bisphosphonate therapy within 4 weeks prior to first dose of study
             treatment. Participants receiving ongoing bisphosphonate or denosumab therapy must
             have been on stable doses for at least 4 weeks prior to receiving first dose of study
             treatment. Participants on stable doses of bisphosphonates who show subsequent tumor
             progression may continue on this medication.

          -  Impaired cardiac function or clinically significant cardiac diseases, including any of
             the following:

               1. History or presence of serious uncontrolled ventricular arrhythmias or presence
                  of uncontrolled atrial fibrillation.

               2. Clinically significant resting bradycardia (< 50 beats per minute).

               3. Any of the following within 3 months prior to study entry: myocardial infarction
                  severe/unstable angina, Coronary Artery Bypass Graft, Grade 3 or 4 Congestive
                  Heart Failure, Cerebrovascular Accident, Transient Ischemic Attack, or Pulmonary
                  Embolism.

               4. Uncontrolled hypertension, as defined by a systolic blood pressure > 160 mm Hg
                  and/or a diastolic blood pressure > 90 mm Hg with or without anti-hypertensive
                  medication.

               5. Previous pericarditis; clinically significant pleural effusion in the previous 12
                  months or current ascites requiring 2 or more interventions per month.

               6. Angina at rest.

          -  Any acute toxicities due to prior chemotherapy and/or radiotherapy that have not
             resolved to a National Cancer Institute (NCI) common terminology criteria for adverse
             events (CTCAE), version 4.03 Grade of ≤ 1. Chemotherapy induced alopecia or Grade 2
             neuropathy is allowed.

          -  Any condition or situation, which in the Investigator's opinion, may put the
             participant at significant risk, confound the study results, or interfere
             significantly with the participant's participation in the study.

          -  Men with a female partner of child-bearing potential, (defined as a sexually mature
             woman who has not undergone a hysterectomy or who has not been naturally
             postmenopausal for at least 12 consecutive months), who as a couple are unable or
             unwilling to employ two forms of highly effective contraception (e.g., male condom
             with spermicide, diaphragm with spermicide, intra-uterine device). Two methods of
             contraception must be used by participants and their partners through the study and
             for 3 months after the end of study treatment.

          -  Body mass index (BMI) < 1.2 m^2, in order to prevent a participant from receiving a
             dose of selinexor > 70 mg/m^2.