Trial record 7 of 173 for:    "Gastrointestinal Stromal Tumors"

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 (TH-CR-410)

This study is currently recruiting participants.
Verified April 2014 by Threshold Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Threshold Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01381822
First received: June 23, 2011
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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. 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. To assess the safety of TH-302 in combination with sunitinib and determine a recommended Phase 2 dose of the combination.

The secondary objectives are:

Dose expansion:

1. To make a preliminary assessment of the efficacy of TH-302 in combination with sunitinib as determined by stable disease or better rate, duration of response and overall survival in subjects with advanced RCC treated at the RP2D.

The exploratory objective is:

1. To explore the association of serum hypoxia biomarkers with efficacy endpoints.


Condition Intervention Phase
Advanced Renal Cell Carcinoma
Gastrointestinal Stromal Tumors
Pancreatic Neuroendocrine Tumors
Drug: TH-302
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Dose-Escalation Study to Determine the Safety of TH-302 in Combination With Sunitinib in Patients With Advanced Renal Cell Carcinoma,Gastrointestinal Stromal Tumors and Pancreatic Neuroendocrine Tumors

Resource links provided by NLM:


Further study details as provided by Threshold Pharmaceuticals:

Primary Outcome Measures:
  • To determine the MTD and DLT(s) of TH-302 when used in combination with sunitinib. [ Time Frame: Two years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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. [ Time Frame: Two years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 58
Study Start Date: June 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TH-302 Dose escalation
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
TH-302: administered by IV infusion over 30 or 60 minutes on Days 8, 15 and 22 of a 42 day cycle.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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,
  • Acceptable hematologic status (without hematologic support):

    • ANC greater than or equal to 1500 cells/μL
    • Platelet count greater than or equal to 100,000/μL
    • Hemoglobin great than or equal to 9.0 g/dL
  • Acceptable cardiac function:

    • Normal 12-lead ECG (clinically insignificant abnormalities permitted)
    • LVEF normal by MUGA or echocardiogram
  • Urinalysis: No clinically significant abnormalities
  • Acceptable thyroid function
  • All women of childbearing potential must have a negative serum pregnancy test and all subjects must agree to use effective means of contraception (surgical sterilization or the use or barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose

Exclusion Criteria:

  • 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
  • Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
  • Prior therapy with an hypoxic cytotoxin
  • Subjects who participated in an investigational drug or device study within 21 days prior to study entry
  • Known infection with HIV or active infection with hepatitis B or hepatitis C
  • Subjects who have exhibited allergic reactions to a structural compound or biological agent similar to TH-302
  • Females who are pregnant or breast-feeding
  • Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
  • Unwillingness or inability to comply with the study protocol for any reason
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01381822

Contacts
Contact: Stephanie Mar 650-474-8221 smar@Thresholdpharm.com

Locations
United States, Indiana
IU Health Goshen Center for Cancer Care Recruiting
Goshen, Indiana, United States, 46526
Contact: Rebecca Eickhoff    574-364-2649    Reickhoff@iuhealth.org   
Principal Investigator: Alexander Starodub, MD         
IU Simon Cancer Center Withdrawn
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Deborah Pearson    319-356-4797    deborah-pearson@uiowa.edu   
Principal Investigator: Mohammed Milhem, MD         
Sponsors and Collaborators
Threshold Pharmaceuticals
Investigators
Principal Investigator: Alexander Starodub, MD IU Health Goshen Center for Cancer Care
Principal Investigator: Mohammed Milhem, MD University of Iowa
  More Information

Additional Information:
No publications provided

Responsible Party: Threshold Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01381822     History of Changes
Other Study ID Numbers: TH-CR-410
Study First Received: June 23, 2011
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Threshold Pharmaceuticals:
TH-302
Advanced Renal Cell Carcinoma
RCC
Gastrointestinal Stromal Tumors
GIST
Phase 1
Sunitinib
Pancreatic Neuroendocrine Tumors
PNET

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Carcinoma
Carcinoma, Renal Cell
Neuroendocrine Tumors
Adenoma, Islet Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Adenoma
Pancreatic Neoplasms
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases
Sunitinib
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014