Phase I Study of KPT330 in Asian Patients

NCT02078349 | Completed Phase 1 DMC

• 2 other identifiers: KPT330-A12013/01034
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Number of participants with Adverse Events

  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.

  up to 12 months

Secondary Outcomes (1)

• Time to reach Cmax (Peak Plasma Concentration) of KPT-330 (Selinexor)

  2 months

Study Arms (1)

Solid Tumors

EXPERIMENTAL

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

Interventions

KPT-330 DRUG

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.

Also known as: Selinexor

Solid Tumors

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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.
• Hepatic function: bilirubin \< 2.0 times the upper limit of normal (ULN), ALT \< 2.5 times ULN
• Up to 10% deviation is acceptable
• 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.
• Amylase and lipase ≤ 1.5 x ULN;
• Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer);
• 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.

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• Karyopharm Therapeutics Inc: collaborator

Study Sites (1)

National University Hospital

Singapore, 119228, Singapore

Location

Related Publications (2)

• Turner JG, Dawson J, Sullivan DM. Nuclear export of proteins and drug resistance in cancer. Biochem Pharmacol. 2012 Apr 15;83(8):1021-32. doi: 10.1016/j.bcp.2011.12.016. Epub 2011 Dec 20.

  PMID: 22209898 BACKGROUND

• Golomb L, Bublik DR, Wilder S, Nevo R, Kiss V, Grabusic K, Volarevic S, Oren M. Importin 7 and exportin 1 link c-Myc and p53 to regulation of ribosomal biogenesis. Mol Cell. 2012 Jan 27;45(2):222-32. doi: 10.1016/j.molcel.2011.11.022.

  PMID: 22284678 BACKGROUND

MeSH Terms

Interventions

selinexor

Study Officials

• Boon Cher Goh, MBBS

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2014
• First Posted: March 5, 2014
• Study Start: February 1, 2014
• Primary Completion: March 20, 2020
• Study Completion: March 20, 2020
• Last Updated: September 10, 2020

Record last verified: 2020-09

Locations

SG (1)