Clinical trial NCT01262235: A Dose Finding Study of TKM-080301 Infusion in Neuroendocrine Tumors (NET) and Adrenocortical Carcinoma (ACC) Patients
Official title: A Phase 1/2 Dose Escalation Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of Intravenous TKM-080301 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cancer
Neuroendocrine Tumors
NET
Adrenocortical Carcinoma
ACC
Keywords: Solid tumor
Non-Hodgkin's Lymphoma
Hodgkin's Disease
Neuroendocrine tumors (NET)
Adrenocortical carcinoma (ACC)
Carcinoid
Lead sponsor: Arbutus Biopharma Corporation
Sponsor class: INDUSTRY
First posted: 2010-12-17
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Safety and tolerability of treatment with TKM-080301
timeFrame: 6 months
measure: Determine dose-limiting toxicities and maximum tolerated dose of TKM-080301
timeFrame: 6 months
Secondary outcomes:
measure: Characterize the pharmacokinetics of TKM-080301
timeFrame: 2 months
measure: Assess preliminary evidence of anti-tumor activity
timeFrame: 6 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Healthcare Research Institute
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Iowa City
country: United States
facility: University of Iowa/Holden Comprehensive Cancer Center
state: Iowa
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Houston
country: United States
facility: Westchase Oncology Center
state: Texas
Study officials:
affiliation: Tekmira Pharmaceuticals
name: Mark Kowalski, MD
role: STUDY_DIRECTOR
References: