AzTrials
AzTrials

Non-small Cell Lung CancerPhase 1/2NCT03095612

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

A Phase 1/2 study testing Selinexor and Docetaxel in people with Non-small Cell Lung Cancer, run by University of Texas Southwestern Medical Center at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
Selinexor and Docetaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
5 sitesUnited States
Study dates
22 Mar 2018to 3 Mar 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must meet all of the following inclusion criteria to be eligible to enroll in this study:
  • 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).
Show all 21Show fewer
  • 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.
  • 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).
  • Measurable disease according to RECIST v1.1
  • 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.
  • 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
  • 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

Who cannot join

  • Patients meeting any of the following exclusion criteria are not eligible to enroll in this study:
  • 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:
Show all 17Show fewer
  • 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)
  • Patients unwilling to comply with study protocol.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75063

  • University of Vanderbilt Medical Center-Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • University of Pittsburgh Medical Center-Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • University of Washington-Seattle Cancer Care Alliance

    Seattle, Washington, 98195

Other trials in United States

About this study

Official title: An Investigator-sponsored, Phase 1/2 Trial of the Oral XPO1 Inhibitor Selinexor (KPT-330) Monotherapy and in Combination With Docetaxel for Previously Treated, Advanced KRAS Mutant Non-small Cell Lung Cancer (NSCLC)

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.

Read the 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).

Being tested
Selinexor, Docetaxel
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SelinexorDrug

    Also called KPT-330

    Selinexor once weekly oral or twice weekly oral

  • DocetaxelDrug

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

Study groups in NCT03095612
Study groupRoleWhat they receive
Selinexor Monotherapy and in Combination with DocetaxelExperimentalFor 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.
Receives: Drug: Selinexor; Drug: Docetaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Each 21 day cycle for 2 years

Secondary outcomes (1)

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

    To evaluate the efficacy of selinexor monotherapy and in combination with docetaxel in patients with advanced KRAS mutant NSCLC. Tumor size will be assessed at baseline and every 2 cycles (ie, after 7 weeks for first 2 cycles, and then every 6 weeks) during the treatment period using the Response Evaluation Criteria in Solid Tumors RECIST v1.1 criterion.

    Measured: Each 21 day cycle for 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Mar 2017
  2. Study start22 Mar 2018
  3. Primary completion8 Nov 2022
  4. Study completion3 Mar 2023

Why it stopped: Funding Sponsor no longer supporting study

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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.
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03095612
Sponsor's protocol ID
STU 032017-003
Status last verified
Jun 2024
First submitted
23 Mar 2017
Last updated
13 Jun 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Selinexor and Docetaxel in people with Non-small Cell Lung Cancer, run by University of Texas Southwestern Medical Center at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 13 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose Limiting Toxicities (DLT) (time frame: Each 21 day cycle for 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03095612.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in