Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 2 for:    selinexor | Colo-rectal Cancer

Bioequivalence and the Tolerability and Antitumor Activity of Selinexor Combination Treatment (SPRINT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04256707
Recruitment Status : Recruiting
First Posted : February 5, 2020
Last Update Posted : February 5, 2020
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc

Brief Summary:
This is a Phase 1, two-part, two-arm, open-label study in patients with NSCLC who have had 1 or 2 prior lines of treatment, with 1 line containing a CPI, or patients with CRC who have had 2 prior lines of treatment (oxaliplatin- and irinotecan-based) and no prior immunotherapy. The study will comprise 2 treatment periods (Monotherapy and Combination Therapy). During the Monotherapy Period, the bioequivalence/relative bioavailability of different formulations of selinexor will be evaluated using a 2-sequence crossover design. During the Combination Therapy Period, the safety and preliminary anti-tumor activity of selinexor in combination with docetaxel (for patients with NSCLC) or pembrolizumab (for patients with CRC) will be evaluated.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Carcinoma (NSCLC) Colorectal Cancer (CRC) Drug: Selinexor Drug: Docetaxel Drug: Pembrolizumab Phase 1

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Two part study (monotherapy period and combination therapy period).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-Label, Phase 1 Study Evaluating the Bioequivalence of Different Formulations of Selinexor, and the Tolerability and Antitumor Activity of Selinexor Combination Treatment (SPRINT)
Actual Study Start Date : January 14, 2020
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Monotherapy: Formulation Arm 1
  • Week 1: selinexor 5 x 20-mg tablet daily;
  • Week 2: selinexor 1 x 100-mg tablet daily;
  • Week 3: selinexor 100-mg oral suspension OR 5 x 20-mg tablet
Drug: Selinexor

100-mg once weekly in the following 3 formulations:

  • 5 × 20-mg tablets (Tablet A)
  • 1 × 100-mg tablet (Tablet B)
  • A 100-mg dose of a suspension (Suspension C)
Other Name: Xpovio®

Experimental: Monotherapy: Formulation Arm 2
  • Week 1: selinexor 1 x 100-mg tablet daily;
  • Week 2: selinexor 5 x 20-mg tablet daily;
  • Week 3: selinexor 100-mg oral suspension OR 5 x 20-mg tablet
Drug: Selinexor

100-mg once weekly in the following 3 formulations:

  • 5 × 20-mg tablets (Tablet A)
  • 1 × 100-mg tablet (Tablet B)
  • A 100-mg dose of a suspension (Suspension C)
Other Name: Xpovio®

Experimental: Combination Therapy: NSCLC Cohort
Selinexor 60 mg oral dose once weekly and docetaxel 75 mg/m² IV once every 3 weeks (NSCLC patients)
Drug: Selinexor

100-mg once weekly in the following 3 formulations:

  • 5 × 20-mg tablets (Tablet A)
  • 1 × 100-mg tablet (Tablet B)
  • A 100-mg dose of a suspension (Suspension C)
Other Name: Xpovio®

Drug: Docetaxel
75 mg/m² IV once every 3 weeks
Other Name: Taxotere®

Experimental: Combination Therapy: CRC Cohort
Selinexor 80 mg oral does once weekly and pembrolizumab 200 mg IV every 3 weeks (CRC patients)
Drug: Selinexor

100-mg once weekly in the following 3 formulations:

  • 5 × 20-mg tablets (Tablet A)
  • 1 × 100-mg tablet (Tablet B)
  • A 100-mg dose of a suspension (Suspension C)
Other Name: Xpovio®

Drug: Pembrolizumab
200 mg IV every 3 weeks
Other Name: Keytruda®




Primary Outcome Measures :
  1. Monotherapy Period: Determine the bioequivalence of two selinexor tablet formulations [ Time Frame: 2 weeks ]
    Bioequivalence for selinexor 20 mg and 100 mg tablets will be assessed at 100 mg weekly based on blood samples collected predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 24, 30, and 48 hours post-selinexor dose on Days 1 and 8. The following pharmacokinetic (PK) parameters will be evaluated: area under the concentration-time curve (AUC) from time 0 to time of last concentration measured (AUC0-t), AUC from time 0 extrapolated to infinity (AUC0-inf), and maximum plasma concentration (Cmax).

  2. Combination Therapy Period: Evaluate safety and tolerability of selinexor in combination with docetaxel in patients with NSCLC or pembrolizumab in patients with CRC [ Time Frame: Patients will be followed for up to 1 year after the 30-Day Safety Visit (approximately 30 days after the last dose of combination therapy) ]
    The safety and tolerability of selinexor in combination with docetaxel or pembrolizumab will be assessed in patients with NSCLC or CRC, respectively, based on AE reports, physical examination results (including vital signs), and clinical laboratory results by means of the occurrence, nature and severity of AEs.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

Patients are eligible to be included in the study only if they meet all of the following criteria:

  1. Are ≥18 years of age.
  2. Have histologically confirmed advanced or metastatic NSCLC or CRC (patients with either KRAS mutation or wild type are eligible; however, at least 10 patients with CRC must have KRAS-mutant disease).
  3. Patients must have evidence of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
  4. Have received prior therapy as follows:

    1. For patients with NSCLC, have received at least 1 but no more than 2 prior line(s) of systemic anti-cancer treatment with 1 regimen including a checkpoint inhibitor (CPI).
    2. For patients with CRC, have received 2 prior lines of systemic anti-cancer treatment (oxaliplatin- and irinotecan-based); no prior therapy with immunotherapy.
  5. Female patients of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective (dual methods of) contraception throughout the study and for 1 week following the last dose of study drug; and male patients must use an effective barrier method of contraception throughout the study and for 1 week following the last dose of study drug if sexually active with a female of childbearing potential.
  6. Willing to provide written informed consent in accordance with federal, local, and institutional guidelines and comply with all requirements of the trial.

Key Exclusion Criteria:

Patients are excluded from the study if any of the following criteria apply:

  1. Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≥2.
  2. Have a life expectancy of <12 weeks, as determined by the Investigator.
  3. Have inadequate hepatic function defined as total bilirubin, aspartate aminotransferase (AST), or alanine aminotransferase (ALT) > upper limit of normal (ULN). Patients with mild hepatic dysfunction (total bilirubin of 1 - 1.5 × ULN or AST/ALT of 1 - 2 × ULN) may be included in the study if approved by the Sponsor's Medical Monitor.
  4. Have inadequate hematopoietic function defined as absolute neutrophil count (ANC) <1.5 × 10⁹/L; platelet count (PLT) <100 × 10⁹/L; or hemoglobin (Hb) <9 g/dL.
  5. Had transfusions or hematopoietic growth factors <7 days of Day 1 dosing.
  6. Have inadequate renal function defined as a calculated creatinine clearance (CrCl) of <20 mL/min using the formula of Cockcroft and Gault.
  7. Have any other medical condition especially any gastrointestinal (GI) dysfunctions or GI disease that could interfere with the absorption of selinexor (e.g., inability to swallow tablets, malabsorption syndrome, a history of GI surgery which may result in intestinal blind loop, significant gastroparesis, unresolved nausea, vomiting, or diarrhea [National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade >1]) or have any general inability to swallow and retain oral medications.
  8. Unstable cardiovascular function:

    1. symptomatic ischemia, or
    2. congestive heart failure of New York Heart Association Class ≥3, or
    3. myocardial infarction within 3 months of Day 1 dosing.
  9. Received strong cytochrome P450 3A (CYP3A) inhibitors OR strong CYP3A inducers ≤7 days prior to Day 1 dosing.
  10. Ongoing infection requiring parenteral antibiotics, antivirals, or antifungals on Day 1 dosing.
  11. Insufficient time since or not recovered from procedures or anti-cancer therapy, defined as:

    1. Not recovered from major surgery ≤21 days prior to Day 1 dosing. Minor procedures, such as biopsies, dental work, or placement of a port or intravenous line for infusion are permitted.
    2. Have ongoing clinically significant anti-cancer therapy-related toxicities CTCAE Grade >1. In specific cases, patients whose toxicity has stabilized or with Grade 2 non-hematologic toxicities can be allowed following documented approval by the Sponsor's Medical Monitor.
    3. Had last dose of previous anti-cancer therapy ≤14 days prior to Day 1 dosing.
  12. Inability or unwillingness to undergo a series of PK sampling.
  13. Inability or unwillingness to take supportive medications such as anti-nausea and anti-anorexia agents as recommended by the NCCN Clinical Practice Guidelines in Oncology for antiemesis and anorexia/cachexia (palliative care).
  14. Serious psychiatric or medical conditions that could interfere with participation in the study or in the opinion of the Investigator would make study involvement unreasonably hazardous.
  15. In the opinion of the Investigator, patients who are significantly below their ideal body weight.
  16. Known allergy to selinexor (all patients), docetaxel (NSCLC Cohort only), or pembrolizumab (CRC Cohort only).
  17. Female patients who are pregnant or lactating.
  18. Patients with CRC who are to receive pembrolizumab:

    1. had a diagnosis of immunodeficiency or are receiving systemic steroid therapy (>10 mg/day of prednisone or equivalent) or any other form of immunosuppressive therapy.
    2. are diagnosed with endocrinopathies, such as abnormal thyroid function. Patients on stable hormone replacement therapy are allowed.
    3. have active autoimmune disease requiring systemic treatment during the past 2 years. Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted.

    The following exclusion criteria define patients to be excluded from the Combination Therapy Period upon completion of the Monotherapy Period:

  19. Have PLT <100 × 10⁹/L, ANC <1.0 × 10⁹/L (for patients with NSCLC who are to receive docetaxel, ANC <1.5 × 10⁹/L), or Hb <9 g/dL.
  20. Have an ECOG performance status of ≥3.
  21. Have not recovered or stabilized from nonhematologic toxicities related to selinexor, with recovery defined as Grade 1 or baseline for nonhematologic AEs. Patients with certain Grade 2 nonhematologic toxicities can be allowed following approval by the Sponsor's Medical Monitor.

    Note: Dose interruption between the Monotherapy Period and the Combination Therapy Period is allowed for recovery from AEs. Patients requiring >21 days after the End of Monotherapy Treatment visit to recover from toxicities related to selinexor should be discussed with the Sponsor's Medical Monitor for approval to continue to the Combination Therapy Period.

  22. For patients with CRC who are to receive pembrolizumab, have received live-attenuated vaccine against an infectious disease (e.g., influenza) ≤14 days prior to Cycle 1 Day 1 (C1D1).
  23. For patients with NSCLC who are to receive docetaxel, have a bilirubin >ULN or AST and/or ALT >1.5 × ULN concurrent with alkaline phosphatase >2.5 × ULN.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04256707


Contacts
Layout table for location contacts
Contact: Michael Kauffman, MD, PhD (617) 658-0600 mkauffman@karyopharm.com
Contact: Sharon Shacham, PhD, MBA (617) 658-0600 sshacham@karyopharm.com

Locations
Layout table for location information
Israel
Soroka University Medical Center Recruiting
Beer-Sheva, Israel, 84101
Contact: Nir Peled       peled.nir@gmail.com; drnp@012.net.il; nirp@clalit.org.il   
Principal Investigator: Nir Peled         
Rambam Health Care Campus Recruiting
Haifa, Israel, 3109601
Contact: Corinne Maurice-Dorr    972.4.7776473    c_maurice-dror@rambam.health.gov.il   
Principal Investigator: Corinne Maurice-Dorr         
Sheba Medical Center Recruiting
Tel-Hashomer, Israel, 5265601
Contact: Talia Golan    972.3.5305338    Talia.Golan@sheba.health.gov.il   
Principal Investigator: Talia Golan         
Sponsors and Collaborators
Karyopharm Therapeutics Inc
Investigators
Layout table for investigator information
Study Director: Michael Kauffman, MD, PhD Karyopharm Therapeutics Inc

Layout table for additonal information
Responsible Party: Karyopharm Therapeutics Inc
ClinicalTrials.gov Identifier: NCT04256707    
Other Study ID Numbers: KCP-330-027
XPORT-STP-027 ( Other Identifier: Karyopharm )
First Posted: February 5, 2020    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: February 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Karyopharm Therapeutics Inc:
non-small cell lung carcinoma
selinexor
docetaxel
colorectal cancer
KPT-330
bioequivalence
relative bioavailability
pharmacokinetics
Additional relevant MeSH terms:
Layout table for MeSH terms
Colorectal Neoplasms
Lung Neoplasms
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Respiratory Tract Neoplasms
Thoracic Neoplasms
Bronchial Neoplasms
Carcinoma, Non-Small-Cell Lung
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Docetaxel
Pembrolizumab
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological