Dose-Escalation Study of TH-302 in Combination With Sunitinib to Treat Patients With Advanced Renal Cell Carcinoma,Gastrointestinal Stromal Tumors and Pancreatic Neuroendocrine Tumors

NCT01381822 | Unknown Phase 1

• 1 other identifier: TH-CR-410
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 2

Brief Summary

The primary objectives are: Dose escalation: 1\. To determine the MTD and DLT(s) of TH-302 when used in combination with sunitinib. Dose expansion:

1. 1.To make a preliminary assessment of the efficacy of TH-302 in combination with sunitinib as determined by the response rate and the progression-free survival in subjects with advanced RCC treated at the RP2D
2. 2.To assess the safety of TH-302 in combination with sunitinib and determine a recommended Phase 2 dose of the combination.

Conditions

Advanced Renal Cell Carcinoma; Gastrointestinal Stromal Tumors; Pancreatic Neuroendocrine Tumors

Keywords

TH-302; Advanced Renal Cell Carcinoma; RCC; Gastrointestinal Stromal Tumors; GIST; Phase 1; Sunitinib; Pancreatic Neuroendocrine Tumors; PNET

Outcome Measures

Primary Outcomes (1)

• To determine the MTD and DLT(s) of TH-302 when used in combination with sunitinib.

  Two years

Secondary Outcomes (1)

• To make a preliminary assessment of the efficacy of TH-302 in combination with sunitinib as determined by the response rate and the progression-free survival in subjects with advanced RCC treated at the RP2D.

  Two years

Study Arms (1)

TH-302 Dose escalation

EXPERIMENTAL

The initial dose of TH-302 will be 240 mg/m2. A Dose Level minus 1 and 2 will be built into the study in the event that subjects experience excessive toxicity at Dose Level 1. Dose escalation will continue with approximately 40% increases from the previous dose level; however lower dose increases of 20-39% may be implemented after consultation between the Investigators, Medical Monitor and Sponsor with the percent increase dependent on the current dose level and the cumulative safety data.

Drug: TH-302

Interventions

TH-302 DRUG

TH-302: administered by IV infusion over 30 or 60 minutes on Days 8, 15 and 22 of a 42 day cycle.

TH-302 Dose escalation

Eligibility Criteria

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

You may qualify if:

• At least 18 years of age
• Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee
• Pathologically confirmed diagnosis of
• advanced RCC or
• GIST after disease progression on or intolerance to imatinib mesylate (dose escalation only)
• Unresectable locally advanced or metastatic pancreatic neuroendocrine tumors (dose escalation only)
• Recovered from reversible toxicities of prior therapy
• Evaluable disease by RECIST criteria (at least one target or non-target lesion for dose escalation cohorts; at least 1 target lesion for dose expansion cohort)
• ECOG performance status of 0 - 2
• Life expectancy of at least 3 months
• Acceptable liver function:
• Bilirubin less than or equal to 1.5 times upper limit of normal (ULN)
• AST (SGOT) and ALT (SGPT) less than or equal to 3.0 times ULN
• Acceptable renal function:
• Serum creatinine ≤ Upper Limit Normal,

You may not qualify if:

• Prior therapy with more than 2 myelosuppressive cytotoxic chemotherapy regimens (does not include neoadjuvant and adjuvant therapy)
• Current use of drugs with known cardiotoxicity or known interactions with sunitinib (see product label)
• Anticancer treatment with radiation therapy, chemotherapy, targeted therapies (erlotinib, lapatinib, etc.), immunotherapy, hormones or other antitumor therapies within 3 weeks prior to study entry (6 weeks for nitrosoureas or mitomycin C)
• Significant cardiac dysfunction:
• Cardiac events within 12 months prior to treatment including MI and severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic CHF, cerebrovascular accident or transient ischemic attack or pulmonary embolism
• \> Grade 2 QTc prolongation
• Requirement for antiarrhythmics
• Uncontrolled arrhythmias within the past 6 months
• Angina pectoris requiring antianginal medication within the past 6 months
• Clinically significant valvular heart disease
• Poorly controlled hypertension despite adequate blood pressure medication
• Seizure disorders requiring anticonvulsant therapy
• Known brain metastases (unless previously treated and well controlled for a period of greater than or equal to 3 months)
• Other active malignancy, except for adequately treated non-melanoma skin cancer, in situ cancer
• Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation \<90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause normal tissue hypoxia

Sponsors & Collaborators

• Threshold Pharmaceuticals: lead

Study Sites (2)

IU Health Goshen Center for Cancer Care

Goshen, Indiana, 46526, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Related Links

• Threshold Pharmaceuticals Company Website

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors; Neuroectodermal Tumors, Primitive

Interventions

TH 302

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Alexander Starodub, MD

  IU Health Goshen Center for Cancer Care

  PRINCIPAL INVESTIGATOR

• Mohammed Milhem, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 23, 2011
• First Posted: June 27, 2011
• Study Start: June 1, 2011
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: April 21, 2014

Record last verified: 2014-04

Locations

US (2)