Phase 1/2 Trial of Selinexor (KPT-330) With Docetaxel for Non-small Cell Lung Cancer (NSCLC)

NCT03095612 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: STU 032017-003
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 5

Brief Summary

This study is being done to evaluate the safety of the investigational study drug, selinexor when given with docetaxel to patients who have been previously treated for advanced KRAS mutant lung cancer.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose Limiting Toxicities (DLT)

  A DLT was any Grade 3 or 4 adverse event (AE) using the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0). DLTs were collected to determine the Maximum-Tolerated Dose (MTD). \*\*DLT will include the following when considered to be at least possibly related to study drug administration: 1) \> 1 missed doses (out of 4 doses) of study treatment during cycle 1 due to study treatment related toxicities 2) Discontinuation of study therapy before completion of Cycle 1, due to study-drug related toxicity.

  Each 21 day cycle for 2 years

Secondary Outcomes (1)

• Tumor Size Will be Assessed Using the RECIST v1.1

  Each 21 day cycle for 2 years

Study Arms (1)

Selinexor Monotherapy and in Combination with Docetaxel

EXPERIMENTAL

For the selinexor monotherapy cohort, 6 patients each will be treated in two dosing cohorts (weekly and biweekly). Selinexor once weekly oral (40mg, 60mg, 80mg) OR Selinexor twice weekly oral (60mg, 40mg, 60mg weekly). Selinexor will be administered once weekly starting one week before chemotherapy initiation in combination with docetaxel. Docetaxel will be given once every 3 weeks. Treatment will be administered in 21-day cycles. Selinexor dose escalation: 60, 80, 40 mg once weekly. Docetaxel 75 mg/m2 IV, 60 every 3 weeks.

Drug: Selinexor; Drug: Docetaxel

Interventions

Selinexor DRUG

Selinexor once weekly oral or twice weekly oral

Also known as: KPT-330

Selinexor Monotherapy and in Combination with Docetaxel

Docetaxel DRUG

Docetaxel once every 3 weeks (75 mg/m2 IV)

Selinexor Monotherapy and in Combination with Docetaxel

Eligibility Criteria

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

You may qualify if:

• Written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure. However, the Investigator should not repeat procedures that are performed as part of standard of care (SOC), if they are within the screening window and are done prior to signing the ICF.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Histologically or cytologically confirmed advanced (stage 4, according to the American Joint Committee on Cancer \[AJCC\] version 7.0 Staging manual) NSCLC
• Molecular identification of a KRAS mutation (codons 12, 13, or 61 mutations detected by sequencing) by a CLIA-certified assay (source documentation required).
• Tissue available for analysis at time of enrollment for biomarker analysis: 10 unstained slides plus 1 H+E slide. If archival tumor tissue is not available in select cases, subjects may be permitted to enroll on the study with prior approval of the study PI.
• At least one and up to two previous lines of systemic cytotoxic therapy for advanced NSCLC, of which one must have been a platinum-based doublet therapy. Up to four total previous lines of systemic therapy (including immunotherapy and molecularly targeted therapy) for advanced NSCLC.
• Radiographic or clinical disease recurrence or progression during or after the last line of systemic therapy
• Adequate hematologic function (absolute neutrophil count \[ANC\] ≥ 1500 cells/µL; hemoglobin ≥ 9 g/dL; platelets ≥ 100,000/µL. Patients may be transfused with PRBCs up to 7 days prior to when enrollment labs are drawn to achieve Hgb ≥9.0 mg/dL.
• Adequate renal function (calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation)
• Adequate hepatic function (total bilirubin ≤ upper limit of normal \[ULN\], alanine aminotransferase \[ALT\] ≤ 2 × ULN and aspartate aminotransferase \[AST\] ≤ 2 × ULN). ALT and/or AST may be ≤ 5 × ULN if due to liver metastases. If ALT or AST is \> 2 and ≤ 5 × ULN in patients with liver metastases, alkaline phosphatase must be ≤ 2.5 × ULN (unless elevated alkaline phosphatase clearly due to skeletal-rather than hepatic-process; eg, normal GGT, presence of multiple bone metastases, absence of bulky and/or central liver metastases). Patients with Gilbert's syndrome are allowed if total bilirubin ≤ 2 × ULN and direct bilirubin is ≤ ULN.
• Female patients of childbearing potential must agree to use 2 methods of contraception (including 1 highly effective and 1 effective method of contraception) and have a negative serum pregnancy test at Screening. Male patients must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose of study treatment. Female patients of child-bearing potential must have a negative serum pregnancy test at screening and agree to use 2 reliable methods of contraception throughout the study and for 3 months after their last dose of medication. Female patients are considered NOT of childbearing potential if they have a history of surgical sterility (including hysterectomy and/or bilateral oophorectomy, but not tubal ligation alone) or evidence of post-menopausal status defined as any of the following:
• Natural menopause with last menses \>1 year ago
• Radiation-induced oophorectomy with last menses \>1 year ago
• Chemotherapy-induced menopause with last menses \>1 year ago.

You may not qualify if:

• Patients who are pregnant or lactating
• Major surgery (excluding skin biopsies and procedures for insertion of central venous access devices) within 2 weeks of first dose of study drug
• Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety
• Concurrent active malignancy that would interfere with treatment administration or assessment in the opinion of the treating investigator
• Unstable cardiovascular function:
• Symptomatic ischemia, or
• Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmics is excluded; 1st degree AV block or asymptomatic LAFB/RBBB are not excluded; asymptomatic rate controlled atrial fibrillation is not excluded), or
• Congestive heart failure (CHF) of NYHA Class ≥3, or
• Myocardial infarction (MI) within 3 months
• Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; however, prophylactic use of these agents is acceptable even if parenteral
• Pre-existing grade 3 or 4 neuropathy
• Active Hepatitis A, B or C infection
• Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this study)
• Patients unable to swallow tablets, patients with malabsorption syndrome, or any other GI disease or GI dysfunction that could interfere with absorption of study treatment
• Prior exposure to docetaxel, selinexor, or another selective inhibitor of nuclear transport (SINE) compound (NOTE: prior docetaxel exposure permitted in selinexor monotherapy cohort)

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Karyopharm Therapeutics Inc: collaborator

Study Sites (5)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

University of Pittsburgh Medical Center-Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Vanderbilt Medical Center-Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75063, United States

Location

University of Washington-Seattle Cancer Care Alliance

Seattle, Washington, 98195, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

selinexor; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Dr. David Gerber
• Organization: University of Texas Southwestern Medical Center

david.gerber@utsouthwestern.edu

214-648-4180

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Docetaxel will be given once every 3 weeks. Treatment will be administered in 21-day cycles. Dose limiting toxicities (DLTs) will be assessed based on the first cycle (7-day lead-in plus 21-day cycle = 28 days) toxicity using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 4.03. A standard 3 + 3 dose escalation paradigm will be used.

Study Record Dates

• First Submitted: March 23, 2017
• First Posted: March 29, 2017
• Study Start: March 22, 2018
• Primary Completion: November 8, 2022
• Study Completion: March 3, 2023
• Last Updated: June 13, 2024
• Results First Posted: June 13, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)