A Japanese Phase 1 Trial of TH-302 in Subjects With Solid Tumors and Pancreatic Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Merck KGaA
Sponsor:
Collaborator:
Threshold Pharmaceuticals
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01833546
First received: April 12, 2013
Last updated: May 8, 2014
Last verified: May 2014
  Purpose

This is a Japanese Phase 1, open-label, and dose-escalating trial of TH-302 as monotherapy in subjects with solid tumors and in combination with gemcitabine in subjects with pancreatic cancer.


Condition Intervention Phase
Solid Tumor
Pancreatic Cancer
Drug: TH-302 monotherapy
Drug: TH-302
Drug: Gemcitabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Japanese Single Center, Open-label, Phase I Trial of TH-302 Given Intravenously to Subjects With Solid Tumors as Monotherapy or to Subjects With Advanced Pancreatic Cancer in Combination With Gemcitabine

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Number of subjects experiencing Dose Limiting Toxicity [ Time Frame: Time Frame: up to Day 28 of Cycle 1 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of subjects with Treatment-emergent adverse events [ Time Frame: Baseline up to Day 30 after the last dose of study treatment ] [ Designated as safety issue: Yes ]
  • Eastern Cooperative Oncology Group (ECOG) performance status score [ Time Frame: Baseline, Day 1 of each cycle up to Day 14 after the last dose of study treatment ] [ Designated as safety issue: Yes ]
  • Number of subjects with best overall response [ Time Frame: Baseline, Day 1 of Cycle 2, 3, 4 and thereafter Day 1 of every cycle, up to Day 30 after the last dose of study treatment ] [ Designated as safety issue: No ]
  • Number of subjects with disease control [ Time Frame: Baseline, Day 1 of Cycle 2, 3, 4 and thereafter Day 1 of every cycle, up to Day 30 after the last dose of study treatment ] [ Designated as safety issue: No ]
  • Absolute levels of tumor markers such as carbohydrate antigen 19-9 (CA 19-9) [ Time Frame: Baseline, Day 1 of each cycle up to Day 14 after the last dose of study treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: April 2013
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TH-302 Drug: TH-302 monotherapy
TH-302 will be administered weekly at a dose ranging from 240-480 milligram per square meter (mg/m^2) as intravenous infusion over 30 or 60 minutes on Day 1, 8 and 15 of every 28-day cycle until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Experimental: TH-302 plus Gemcitabine Drug: TH-302
TH-302 will be administered weekly at a dose of either 240 or 340 mg/m^2 as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle, until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Drug: Gemcitabine
Gemcitabine will be administered weekly at a dose of 1000 mg/m^2 as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle, until evidence of progressive disease, intolerable toxicity or subject withdrawal.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • At least 20 years of age
  • Signed written informed consent form
  • Histologically or cytologically confirmed advanced or metastatic solid tumor previously treated with one or more standard treatment regimen(s) or for which no effective therapy is available
  • Histologically or cytologically confirmed locally advanced unresectable or metastatic pancreatic adenocarcinoma previously untreated with chemotherapy or systemic therapy
  • Recovered from toxicities of prior anti-cancer treatment to Grade 1 or less
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy of at least 3 months
  • Acceptable liver function, renal function, hematologic status and coagulation status as defined in the protocol
  • No clinically significant abnormalities in urinalysis
  • Effective contraception for both male and female subjects if the risk of conception exists
  • Other inclusion criteria apply

Exclusion Criteria:

  • Prior anti-cancer treatment with more than 3 myelosuppressive cytotoxic chemotherapy regimens
  • Prior treatment with gemcitabine for their advanced or metastatic pancreatic cancer, except for radiosensitizing doses of gemcitabine
  • Prior radiotherapy to more than 30 percent of the bone marrow within 6 months prior to the trial entry
  • Cardiac disease with New York Heart Association (NYHA) Class 3 or 4, within 6 months prior to the trial entry
  • Clinically significant (that is, active) cardiovascular disease
  • Seizure disorders requiring anticonvulsant therapy
  • Known brain, leptomeningeal or epidural metastases (unless previously treated and well controlled for at least 3 months at the trial entry)
  • Previously treated malignancies other than the current disease for at least 5 years at the trial entry
  • Severe chronic obstructive or other pulmonary disease major surgery, within 4 weeks prior to the trial entry, without complete recovery
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
  • Anti-cancer treatment prior to trial entry
  • Participation in an investigational drug or device trial within 4 weeks prior to the trial entry
  • Known infection with human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C
  • A history of allergic reactions
  • Taking a medication that is either moderate or strong inhibitor or inducer of cytochrome P450 (CYP)3A4 or is a sensitive substrate of other cytochrome P450
  • Pregnancy or lactation period
  • Concomitant disease or condition that could interfere with the conduct of the trial, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this trial
  • Unwillingness or inability to comply with the trial protocol for any reason
  • Legal incapacity or limited legal capacity
  • Other exclusion criteria apply
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01833546

Contacts
Contact: Merck KGaA Communication Center +49 6151 72 5200 service@merckgroup.com

Locations
Japan
Research Site Recruiting
Tokyo, Japan
Research Site Not yet recruiting
Tokyo, Japan
Sponsors and Collaborators
Merck KGaA
Threshold Pharmaceuticals
Investigators
Study Director: Medical Responsible Merck Serono Co., Ltd., Japan
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01833546     History of Changes
Other Study ID Numbers: EMR200592-002
Study First Received: April 12, 2013
Last Updated: May 8, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Merck KGaA:
Solid tumor
Pancreatic cancer
TH-302
gemcitabine

Additional relevant MeSH terms:
Pancreatic Neoplasms
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 01, 2014