Clinical trial NCT02667873: A Trial of a Novel XPO1 Inhibitor in Participants With Advanced Solid Tumors
Official title: A Phase 1 Trial of SL-801, a Novel Inhibitor of XPO1 Nuclear Export, in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Stemline Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2016-01-29
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Study SL-801-0115 is a dose-escalation study evaluating multiple doses and schedules of orally administered SL-801 in participants with advanced solid tumors.

Detailed description: Study SL-801-0115 is a first-in-human, dose-escalation study in participants with advanced (that is, metastatic or locally advanced and unresectable) solid tumors that are resistant to or relapsed following available standard systemic therapy or for which there is no standard systemic therapy and additional radiation therapy, or other loco-regional therapies are not considered feasible. Eligible participants will be enrolled and receive treatment with SL-801. SL-801 will be administered orally, and the dose regimen will depend on the cohort in which the participant is enrolled.

The study plans to enroll approximately 70 adult participants at multiple study centers in the United States.

Eligibility criteria: Inclusion Criteria:

* The participant must have histologic or cytologic evidence of a malignant solid tumor and must have disease that is resistant to or relapsed following available standard systemic therapy, or for which there is no standard systemic therapy or reasonable therapy likely to result in clinical benefit.
* The participant must have advanced disease, defined as cancer that is either metastatic, or locally advanced and unresectable (and for which additional radiation therapy or other locoregional therapies are not considered feasible).
* The participant must have disease that is measurable by standard imaging techniques, per the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), or evaluable per RECIST 1.1. (For participants with prior radiation therapy, measurable lesions must be outside of any prior radiation field\[s\], unless disease progression has been documented at that disease site subsequent to radiation.)
* The participant is ≥18 years old.
* The participant has an Eastern Cooperative Oncology Group Performance Status of 0-2.
* The participant has adequate baseline organ function, as demonstrated by the following:

  * Serum creatinine ≤1.5 × institutional upper limit of normal (ULN) or calculated creatinine clearance \>30 milliliters (mL)/minute.
  * Serum albumin ≥2.5 grams/deciliter (g/dL).
  * Bilirubin ≤1.5 × institutional ULN.
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × institutional ULN (participants with hepatic metastases must have AST/ALT ≤5 times ULN).
  * International normalized ratio ≤1.5 or prothrombin time ≤1.5 × ULN; and either partial thromboplastin time or activated partial thromboplastin time (partial thromboplastin time or activated partial thromboplastin time) ≤1.5 × ULN.
* The participant has adequate baseline hematologic function, as demonstrated by the following:

  * Absolute neutrophil count ≥1.5×10\^9/liter (L)
  * Hemoglobin ≥8 g/dL, with no red blood cell transfusions within the prior 14 days.
  * Platelet count ≥100×10\^9/L, with no platelet transfusions within the prior 14 days.
* If the participant is a woman of childbearing potential, she has had a negative serum or urine pregnancy test within 1 week prior to treatment.
* The participant (male and female) agrees to use acceptable contraceptive methods for the duration of time on the study and continue to use acceptable contraceptive methods for 1 month after the last dose of SL-801.
* The participant has signed informed consent prior to initiation of any study-specific procedures or treatment.
* The participant is able to adhere to the study visit schedule and other protocol requirements, including follow-up for survival assessment.

Exclusion Criteria:

* The participant has persistent clinically significant ≥Grade 2 toxicities from previous anticancer therapy (excluding Grade 2 chemotherapy-related neuropathy which is permitted, and excluding Grade 2-3 laboratory abnormalities if they are not associated with symptoms, are not considered clinically significant by the Investigator, and can be managed with available medical therapies).
* The participant has received treatment with chemotherapy, external-beam radiation, or other systemic anticancer therapy within 28 days prior to study entry (Participants with advanced prostate cancer who are receiving luteinizing hormone releasing hormone \[LHRH\] agonists are permitted onto the study and should continue use of these agents during study treatment).
* The participant has received treatment with an investigational systemic anticancer agent within 28 days prior to C1D1.
* The participant has previously received treatment with SL-801 or another investigational agent that inhibits the XPO1/CRM1 pathway.
* The participant has an additional active malignancy that may confound the assessment of the study endpoints. Participants with a past cancer history (active malignancy within 2 years prior to study entry) with substantial potential for recurrence must be discussed with the Sponsor before study entry. Participants with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including transitional cell carcinoma, cervical intraepithelial neoplasia), organ-confined prostate cancer with no evidence of progressive disease.
* The participant has clinically significant cardiovascular disease (for example, uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
* The participant has uncontrolled, clinically significant pulmonary disease (for example, chronic obstructive pulmonary disease, pulmonary hypertension) that, in the Investigator's opinion, would put the participant at significant risk for pulmonary complications during the study.
* The participant has known active or suspected brain or leptomeningeal metastases. (Central nervous system \[CNS\] imaging is not required prior to study entry unless there is a clinical suspicion of CNS involvement). Participants with stable, treated brain metastases are eligible provided there is no evidence of CNS disease growth on imaging for at least 3 months following radiation therapy or other locoregional ablative therapy to the CNS.
* The participant is receiving immunosuppressive therapy for prophylaxis following a prior organ transplant (solid organ or allogeneic stem cell) or management of immune-mediated toxicities due to immunotherapy. Low-dose corticosteroid (defined as \< 10 mg/day of prednisone or equivalent) therapy is permitted.
* The participant has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness/social situations that would limit compliance with study requirements.
* The participant is pregnant or breast feeding.
* The participant has known positive status for human immunodeficiency virus active or chronic Hepatitis B or Hepatitis C.
* The participant is oxygen dependent.
* The participant has any medical condition which in the opinion of the Investigator places the patient at an unacceptably high risk for toxicities.

Primary outcomes:
measure: safety and tolerability: percentage of patients experiencing treatment-related and treatment-emergent adverse events
timeFrame: up to 5 years
measure: maximum tolerated dose
timeFrame: up to 5 years
Secondary outcomes:
measure: Duration of Response
timeFrame: up to 5 years
measure: Progression Free Survival
timeFrame: up to 5 years
measure: Overall Response Rate
timeFrame: up to 5 years
measure: Overall Survival
timeFrame: up to 5 years
measure: Pharmacokinetic Profile
timeFrame: up to 5 years
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Sarasota
country: United States
facility: Florida Cancer Specialist
state: Florida
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowely Cancer Research Centers- Medical City
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Seattle
country: United States
facility: University of Washington, Seattle Cancer Care Alliance
state: Washington
Study officials:
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