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

Study Overview
=================
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.

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

Conditions
-----------------
NET, ACC, Cancer, Neuroendocrine Tumors, Adrenocortical Carcinoma

Intervention / Treatment
-----------------
* Drug: TKM-080301


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TKM-080301<br> | Drug: TKM-080301<br>* Repeat dose IV infusion.<br>* Other names: TKM-PLK1;|

What is the study measuring?
-----------------
Primary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Carcinoid, Solid tumor, Non-Hodgkin's Lymphoma, Hodgkin's Disease, Neuroendocrine tumors (NET), Adrenocortical carcinoma (ACC)