A Dose Finding Study of TKM-080301 Infusion in Neuroendocrine Tumors (NET) and Adrenocortical Carcinoma (ACC) Patients

A Phase 1/2 Dose Escalation Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of Intravenous TKM-080301 in Patients With Advanced Solid Tumors

This study will be a Phase I/II, open-label, non-randomized, dose-finding trial conducted at multiple clinical centers. The study is designed to determine the safety, tolerability and PK of TKM-080301 in adult patients with solid tumors or lymphomas that are refractory to standard therapy or for whom there is no standard therapy. After the determination of the maximum tolerated dose this dose will be utilized in an expansion cohort or subjects with refractory neuroendocrine tumors (NET) or adrenocortical carcinoma (ACC) tumors.

Study Overview

• Status: Completed
• Conditions: Cancer; Neuroendocrine Tumors; Adrenocortical Carcinoma; ACC; NET
• Intervention / Treatment: Drug: TKM-080301

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona
    • Scottsdale, Arizona, United States, 85258
      • Scottsdale Healthcare Research Institute
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-2800
      • University of Michigan Comprehensive Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Texas
    • Houston, Texas, United States, 77042
      • Westchase Oncology Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have a histologically and cytologically confirmed solid tumor that is refractory to standard therapy or for which no standard therapy is known to exist, or who are not candidates for standard therapy, or non-Hodgkin's lymphoma or Hodgkin's disease that is refractory to standard therapy (i.e., patients have relapsed following at least 2 prior therapies) or for which no standard therapy is known to exist. For the Neuroendocrine (NET) and adrenocortical carcinoma (ACC) expansion cohort subjects must have histologically or cytologically confirmed, measurable (per RECIST 1.1) NET or ACC tumor that is refractory to standard therapy or for which no standard therapy is known to exist, or who are not candidates for standard therapy.
• Patient has an ECOG performance status of 0 - 1,
• Patient has adequate hematologic, hepatic and renal function,
• Patient is seronegative for hepatitis B virus (HBV) and hepatitis C virus (HCV),
• Patients must have a life expectancy of at least 12 weeks.

Exclusion Criteria:

• Unresolved toxicities (> Grade 1) of previous chemotherapy,
• Patients with primary tumors of the central nervous system (CNS),
• Prophylactic hematologic growth factors administered </= 2 weeks prior to start of therapy,
• Patient has history of or existing clinically significant cardiovascular disease,
• Patient has a history of clinically significant asthma or COPD requiring daily medication within the last 6 months,
• Patient has a seizure disorder not controlled on medication,
• Patient has a known or suspected viral, parasitic, or fungal infection,
• Patient has known hypersensitivity or previous severe reactions to oligonucleotide- or lipid-based products, including liposomal drug products and phospholipid-based products,
• Patient has been treated with any investigational drugs, biologics, or devices within 28 days prior to study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TKM-080301	Drug: TKM-080301; Repeat dose IV infusion.; Other Names: PLK1 SNALP; TKM-PLK1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of treatment with TKM-080301	6 months
Determine dose-limiting toxicities and maximum tolerated dose of TKM-080301	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Characterize the pharmacokinetics of TKM-080301	2 months
Assess preliminary evidence of anti-tumor activity	6 months

Collaborators and Investigators

• Sponsor: Arbutus Biopharma Corporation
• Investigators: Study Director: Mark Kowalski, MD, Tekmira Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: December 15, 2010
• First Submitted That Met QC Criteria: December 16, 2010
• First Posted (Estimate): December 17, 2010

Study Record Updates

• Last Update Posted (Actual): January 16, 2019
• Last Update Submitted That Met QC Criteria: January 14, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Solid tumor; Non-Hodgkin's Lymphoma; Hodgkin's Disease; Carcinoid; Adrenocortical carcinoma (ACC); Neuroendocrine tumors (NET)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Adrenal Gland Diseases; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Adrenal Cortex Diseases; Carcinoma; Neuroendocrine Tumors; Adrenocortical Carcinoma
• Other Study ID Numbers: TKM-PLK1-001