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Phase I Study of KPT330 in Asian Patients

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ClinicalTrials.gov Identifier: NCT02078349
Recruitment Status : Recruiting
First Posted : March 5, 2014
Last Update Posted : June 22, 2016
Sponsor:
Collaborator:
Karyopharm Therapeutics Inc
Information provided by (Responsible Party):
National University Hospital, Singapore

Brief Summary:

This is an open-label, dose-escalation (Phase 1a) and expansion (Phase 1b) study to evaluate the safety and tolerability of KPT-330 and determine the recommended phase 2 dose (RP2D) in patients with solid tumor malignancies. The study drug KPT-330 or Selinexor works by blocking high levels of exporter proteins in cancer cells so that the tumor suppressor proteins (TSP, proteins that help to protect cells from becoming cancerous) and growth regulatory proteins (GRP, proteins that help control the growth of cells) will remain in the nucleus in its "activated" form. The idea for using this drug is that the blockage of this export of proteins from the nucleus should result in stopping the growth of tumor cells. Based on its mechanism of action, KPT-330 is a new class of drug called Selective Inhibitor of Nuclear Export (SINE).

The purposes of this research study are to find out more information about the drug such as: the highest dose of KPT-330 that can be given safely, the side effects it may cause, to examine how the body affects the study drug concentrations in the blood (called pharmacokinetics or PK), to examine the effects of this study drug on the body (called pharmacodynamics or PD) and to gain some information on its usefulness in treating cancer.

Benefits of the study include the chance of disease control for patients with treatment refractory cancer for which no other standard treatments are available. Common side effects (35-73%) in humans have mostly been mild and reversible. These include nausea, loss of appetite, fatigue, vomiting and weight loss.


Condition or disease Intervention/treatment Phase
Solid Tumors Drug: KPT-330 Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Investigator Sponsored Phase I Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating Doses Followed by Dose Expansion of the Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Asian Patients With Advanced or Metastatic Solid Tumor Malignancies
Study Start Date : February 2014
Estimated Primary Completion Date : February 2018
Estimated Study Completion Date : February 2019

Arm Intervention/treatment
Experimental: Solid Tumors

Patients will receive Selinexor once weekly (Schedule 1) or twice weekly (Schedule 2) or three times a week (Schedule 3) orally at a starting dose of 50 mg/m² (Schedule 1) and 40mg/m2 (Schedule 2) and 20mg/m2 (Schedule 3).

One cycle is 28 days for Schedule 1 and Schedule 3 and 21 days for Schedule 2. Treatment will continue until disease progression or the development of unacceptable toxicities.

Drug: KPT-330
Each dose will consist of KPT-330 (Selinexor) for oral administration on an mg/m2 basis, and should be based on the patient's actual calculated body surface area (BSA) at baseline. Patients with a BSA >2.5 m(2) will receive a dose based upon a 2.5 m(2) BSA.
Other Name: Selinexor




Primary Outcome Measures :
  1. Number of participants with Adverse Events [ Time Frame: up to 12 months ]
    All adverse events occurring during the course of the trial and for up to one month after the last dose of study medication will be captured, documented, and reported. Toxicity is graded every 2 weeks for the first two cycles and every 4 weeks thereafter, according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.


Secondary Outcome Measures :
  1. Time to reach Cmax (Peak Plasma Concentration) of KPT-330 (Selinexor) [ Time Frame: 2 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All patients must sign an informed consent in accordance with local institutional guidelines
  • Age ≥ 21
  • Dose Escalation Phase: Patients with histologically or cytologically confirmed advanced or metastatic solid tumors who have radiological evidence of progressive disease on study entry that is deemed unlikely to benefit from further conventional therapy, or for which no standard therapy is available.

Dose Expansion Phase: Patients with previously treated, metastatic or advanced recurrent malignancy (including gastric, colorectal, lung, head and neck and gynaecological malignancies) which has been confirmed histologically or cytologically, and who have evidence of progressive disease on study entry that is deemed unlikely to benefit from further conventional therapy, or for which no standard therapy is available. Depending on the total number of patients enrolled in the dose escalation phase, the number of patients recruited in the subsequent dose expansion phase may be adjusted accordingly.

There is no upper limit on the number of prior treatments provided all inclusion/exclusion criteria are met. Hormone ablation therapy is considered an anticancer regimen. Radiation and surgery are not considered anticancer regimens.

  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 1;
  • Patients must have adequate bone marrow function and organ function within 2 weeks of study treatment;

    1. Adequate hematologic function defined as:

      • platelets ≥ 125 x 109/L in dose escalation phase, and platelets ≥ 100 x 10(9)/L in dose expansion phase.
      • hemoglobin ≥ 5.59 mmol/L or 9 g/dL,
      • ANC ≥ 1.5 x 109/L,
      • WBC ≥ 3.0 x 109/L.
      • Up to 5% deviation is tolerated. Transfusions and growth factors are allowed prior to and throughout the study.
    2. Hepatic function: bilirubin < 2.0 times the upper limit of normal (ULN), ALT < 2.5 times ULN

      • Up to 10% deviation is acceptable
    3. Adequate renal function: estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockroft and Gault: (140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female.
    4. Amylase and lipase ≤ 1.5 x ULN;
    5. Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer);
    6. International normalization ratio (INR) (if not on anticoagulation therapy) and partial thromboplastin time (PTT) ≤ 1.5 x ULN;
  • All patients (male and female) of childbearing potential must agree to use adequate birth control (barrier methods) during and for 3 months after participation in this study. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose.

Exclusion Criteria:

  • Patients with significant medical illness that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy;
  • Radiation (except planned or ongoing palliative radiation to bone outside of the region of measurable disease) ≤ 3 weeks prior to cycle 1 day 1
  • Chemotherapy, or immunotherapy or any other systemic anticancer therapy ≤ 3 weeks prior to cycle 1 day 1.
  • Unstable cardiovascular function;
  • Uncontrolled active infection (Hepatitis B and C infection are NOT exclusion criteria).
  • Known HIV infection;
  • Renal failure requiring haemodialysis or peritoneal dialysis;
  • Clinically unstable, active infection requiring systemic antibiotics;
  • Patients who are pregnant or breast-feeding;
  • Concurrent cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off all therapy for that disease for a minimum of 3 years;
  • Patients with significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea or inability to swallow oral medications;
  • Patients with serious psychiatric or medical conditions that could interfere with treatment.
  • History of organ allograft within a period of 6 months or less prior to commencing study
  • Concurrent therapy with approved or investigational anticancer therapeutics;
  • Body weight significantly below ideal body weight in the opinion of the investigator
  • Significant episode of bleeding in the last 4 weeks (e.g. hemorrhoids, epistaxis etc.)

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): NCT02078349


Contacts
Contact: Boon Cher Goh, MBBS (65) 6772 4140/ 6772 4621 Boon_Cher_Goh@nuhs.edu.sg
Contact: David S Tan, MBBS (65) 6772 4661 David_SP_Tan@nuhs.edu.sg

Locations
Singapore
National University Hospital Recruiting
Singapore, Singapore, 119228
Contact: Mei Yan Pang    (65) 6772 3062    mei_yan_pang@nuhs.edu.sg   
Contact: Christine Vergara    (65) 6772 4619    christine_vergara@nuhs.edu.sg   
Sub-Investigator: David SP Tan, MBBS         
Sponsors and Collaborators
National University Hospital, Singapore
Karyopharm Therapeutics Inc
Investigators
Principal Investigator: Boon Cher Goh, MBBS National University Hospital, Singapore