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

NCT ID: NCT03095612

Last Updated: 2024-06-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-22
• Study Completion Date: 2023-03-03

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.

Detailed Description

This is a phase 1/2 single-arm, non-blinded, multi-institutional study. Selinexor will be administered once weekly starting one week before chemotherapy initiation (to permit pharmacodynamic assessment of selinexor alone and in combination with chemotherapy).This study will compare safety and outcomes with historical controls (docetaxel monotherapy).

Conditions

Non-small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Selinexor Monotherapy and in Combination with Docetaxel

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.

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

Selinexor once weekly oral or twice weekly oral

Docetaxel

Intervention Type: DRUG

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

Interventions

Selinexor

Selinexor once weekly oral or twice weekly oral

Intervention Type: DRUG

Docetaxel

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

Intervention Type: DRUG

Other Intervention Names

KPT-330

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Age ≥ 18 years

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

4. Histologically or cytologically confirmed advanced (stage 4, according to the American Joint Committee on Cancer [AJCC] version 7.0 Staging manual) NSCLC

5. Molecular identification of a KRAS mutation (codons 12, 13, or 61 mutations detected by sequencing) by a CLIA-certified assay (source documentation required).

6. 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.

7. 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.

8. Radiographic or clinical disease recurrence or progression during or after the last line of systemic therapy

9. 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.

10. Adequate renal function (calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation)

11. 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.

12. 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.

Male patients and their partners must use 2 reliable methods of contraception, at least one of them a barrier method (if sexually active with a female of child-bearing potential).

13. Measurable disease according to RECIST v1.1

14. Previously treated (surgery and/or radiation therapy) or untreated brain metastases are eligible, provided that patients are asymptomatic and not requiring escalating doses of corticosteroids.

15. Previous treatment-associated clinically significant toxicities resolved to CTCAE grade ≤2 (except alopecia) or to their baseline. NOTE: Prior immunotherapy-related endocrinopathy controlled with ongoing medical management (eg, hypothyroidism, adrenal insufficiency, diabetes) is permitted

16. At least 3 weeks or 5 half-lives, whichever is shorter, since receiving systemic anticancer therapy, including investigational agents, prior to starting study therapy. At least 2 weeks since receiving radiation therapy prior to starting study therapy

Exclusion Criteria

1. Patients who are pregnant or lactating

2. Major surgery (excluding skin biopsies and procedures for insertion of central venous access devices) within 2 weeks of first dose of study drug

3. Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety

4. Concurrent active malignancy that would interfere with treatment administration or assessment in the opinion of the treating investigator

5. 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

6. 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

7. Pre-existing grade 3 or 4 neuropathy

8. Active Hepatitis A, B or C infection

9. Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this study)

10. 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

11. Prior exposure to docetaxel, selinexor, or another selective inhibitor of nuclear transport (SINE) compound (NOTE: prior docetaxel exposure permitted in selinexor monotherapy cohort)

12. Patients unwilling to comply with study protocol.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karyopharm Therapeutics Inc

INDUSTRY

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

David E Gerber

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Colorado Cancer Center

Aurora, Colorado, United States

University of Pittsburgh Medical Center-Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

University of Vanderbilt Medical Center-Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

University of Washington-Seattle Cancer Care Alliance

Seattle, Washington, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

STU 032017-003

Identifier Type: -

Identifier Source: org_study_id