A Phase I Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating Doses of the Selective Inhibitor of Nuclear Export/SINE Compound KPT-330 in Patients With Advanced or Metastatic Solid Tumor Malignancies

Safety Study of KPT-330 in Patients With Advanced or Metastatic Solid Tumor Cancer

Sponsors

Lead sponsor: Karyopharm Therapeutics Inc

Source Karyopharm Therapeutics Inc
Brief Summary

Phase 1 study to evaluate the safety and tolerability of KPT-330 and determine the Recommended Phase 2 Dose (RP2D) of KPT- 330 for advanced or metastatic solid tumor malignancies.

Detailed Description

This is a phase 1a and phase 1b, open-label, dose-escalation study to evaluate the safety and tolerability of KPT-330 and determine the RP2D in patients with solid tumor malignancies.

Overall Status Completed
Start Date June 2012
Completion Date March 2016
Primary Completion Date March 2016
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Number of participants with Adverse Events 2 and 12 months
Secondary Outcome
Measure Time Frame
Area under the plasma concentration versus time curve (AUC) of KPT-330 2 and 12 months
Enrollment 189
Condition
Intervention

Intervention type: Drug

Intervention name: KPT-330

Description: Subjects in this study will receive KPT-330 orally at dose levels specified for their respective dose cohorts. Dosing will begin at 3 mg/m2 twice a week and will escalate until the MTD or RP2D is determined. Cycles will be repeated in four-week (28 day) intervals until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment will be permitted.

Arm group label: Solid Tumors

Other name: Selinexor

Eligibility

Criteria:

Inclusion Criteria:

1. Dose Escalation Phase: Patients with advanced or metastatic solid tumors for which no standard therapy is available. For Schedule 6 only: patients with colorectal cancer with liver metastasis.

Dose Expansion Phase: Previously treated, metastatic or advanced recurrent malignancy with 1 of the following diagnoses, which has been confirmed histologically or cytologically:

- Up to 12 patients with metastatic colorectal cancer with a history of progression or recurrence following prior fluoropyrimidine, irinotecan and platinum containing regimens as well as bevacizumab. In addition, patients with Kras wild type tumor must have received at least one EGFR blocker.

- Up to 6 patients with histological or cytological documentation of advanced ovarian, fallopian tube, or primary peritoneal carcinoma with a history of progression or recurrence following at least one prior platinum and one taxane based chemotherapy

- Up to 12 patients with incurable Squamous cell cancers as follows:

1. A minimum of 4 Squamous Non-Small Cell Lung Cancer (Sq-NSCLC)

2. A minimum of 4 Squamous Cell Carcinomas of the Head and Neck (Sq-HNC)

3. Squamous Cell Carcinoma of the Cervix (SqCC) All patient with Squamous Cell Carcinomas should have a documented history of progression or recurrence following at least one prior platinum based chemotherapy or chemotherapy/radiation containing regimen

- Up to 6 patients with castration-resistant prostate cancer (CRPC) that was pathologically confirmed as adenocarcinoma of the prostate and with evidence of metastatic disease on bone scan or other imaging. Patient must have progressive disease after at least one hormonal treatment and one cytotoxic therapy e.g. with docetaxel, mitoxantrone.

- Up to 6 patients with recurrent/relapsed glioblastoma multiforme (GBM/AnaA) or with grade 3 anaplastic astrocytomas that with a history of progression or recurrence following radiotherapy and an alkylating agent (e.g. temozolomide) Patients with other disease types may be enrolled into the expansion phase upon approval of the Sponsor.

2. Dose Escalation Phase: Patients have exhausted, or be deemed to not benefit from, further conventional therapy and have evidence of progressive disease on study entry.

Both Dose Escalation and Expansion Phases: There is no upper limit on the number of prior treatments provided that all inclusion criteria are met and exclusion criteria are not met. Hormone ablation therapy is considered an anticancer regimen. Radiation and surgery are not considered anticancer regimes.

Exclusion Criteria:

1. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤3 weeks prior to cycle 1 day 1 and mitomycin C and radioimmunotherapy 6 weeks prior to cycle 1 day 1;

2. Except for patients with GBM/ AnaA in the Expansion Phase, patients with active CNS malignancy are excluded. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Michael Kauffman, MD, Ph.D Study Director Karyopharm Therapeutics Inc
Location
facility
Moffitt Cancer Center | Tampa, Florida, 33612, United States
Karmanos Cancer Institute | Detroit, Michigan, 48201, United States
Memorial Sloan-Kettering Cancer Center | New York, New York, 10065, United States
Gabrail Cancer Center | Canton, Ohio, 44718, United States
Princess Margaret Hospital | Toronto, Ontario, M5T 2M9, Canada
Rigshospitalet | Copenhagen, 2100, Denmark
Location Countries

Canada

Denmark

United States

Verification Date

August 2018

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: Solid Tumors

Arm group type: Experimental

Description: KPT-330

Patient Data Yes
Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov