Dose-Escalation Study of TH-302 in Combination With A) Gemcitabine or B) Docetaxel or C) Pemetrexed to Treat Advanced Solid Tumors

NCT00743379 | Completed Phase 1

• 1 other identifier: TH-CR-402
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of this study is to determine if TH-302, in combination with A) Gemcitabine, or B) Docetaxel or C) Pemetrexed methotrexate, are safe and effective in the treatment of Pancreatic Cancer, Castrate-resistant Prostate Cancer, and Non-small Cell Lung Cancer, respectively.

Conditions

Non-Small Cell Lung Cancer; Prostate Cancer; Pancreatic Cancer

Keywords

Phase 1/2; Advanced Solid Tumors; Hypoxia; Prodrug; Dose-Escalation; Evofosfamide

Outcome Measures

Primary Outcomes (1)

• To determine the MTD and DLT(s) of TH-302 when used in combination with A) Gemcitabine or B) Docetaxel or C) Pemetrexed in patients with advanced solid tumors

  Two years

Secondary Outcomes (1)

• To establish the pharmacokinetics of TH-302 , gemcitabine, pemetrexed and docetaxel when used in each of the combinations assessed

  Two years

Study Arms (3)

A

EXPERIMENTAL

TH-302 in combination with Gemcitabine. 1,000 mg/m2 of Gemcitabine is administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle.

Drug: TH-302

B

EXPERIMENTAL

TH-302 in combination with Docetaxel. 75 mg/m2 of Docetaxel is administered IV over 60 minutes on Day 1 of a 21-day cycle.

Drug: TH-302

C

EXPERIMENTAL

TH-302 in combination with Pemetrexed. 500 mg/m2 of Pemetrexed is administered IV over 10 minutes on Day 1 of a 21-day cycle.

Drug: TH-302

Interventions

TH-302 DRUG

TH-302 will be administered by IV infusion over 30 minutes on Days 1, 8 and 15 of a 28- day cycle for Arm A and on Days 1 and 8 of a 21 day cycle for Arms B and C.

A; B; C

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
• Dose escalation subjects:
• a. Histologically or cytologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective OR solid malignancy for which monotherapy with gemcitabine is considered standard therapy b. Tumor progression after most recent therapy
• Dose expansion subjects:
• a. Locally advanced unresectable or metastatic pancreatic ductal adenocarcinoma proven either by histology (surgical biopsy) or cytology (CT- or endoscopic-guided) previously untreated with chemotherapy other than radiosensitizing doses of 5-fluorouracil
• Recovered from toxicities of prior therapy to grade 0 or 1
• Evaluable disease by RECIST criteria (at least one target or non-target lesion)
• ECOG 0 or 1
• Life expectancy of at least 3 months
• Acceptable liver function:
• a. Bilirubin ≤ 1.5 times upper limit of normal b. AST (SGOT) and ALT (SGPT) ≤ 2.5xULN; if liver metastases are present, then ≤ 5xULN is allowed
• Acceptable renal function:
• a. Serum creatinine ≤ ULN
• Acceptable hematologic status:

You may not qualify if:

• All Subjects:
• Prior treatment with more than 3 myelosuppressive cytotoxic chemotherapy regimens
• Prior treatment with gemcitabine
• Prior radiotherapy to more than 25% of the bone marrow
• New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial infarction within 6 months prior to Day 1, unstable arrhythmia or symptomatic peripheral arterial vascular disease
• Seizure disorders requiring anticonvulsant therapy
• Symptomatic brain, leptomeningeal or epidural metastases, (unless previously treated and well controlled for a period of ≥ 3 months)
• Previously treated malignancies, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancer from which the subject has been disease-free for at least 5 years
• 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 systemic or regional hypoxemia
• 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
• Treatment with radiation therapy, surgery, chemotherapy, targeted therapies or hormones within 4 weeks prior to study entry
• Prior therapy with an hypoxic cytotoxin
• Subjects who participated in an investigational drug or device study within 28 days prior to study entry
• Known infection with HIV, hepatitis B or C

Sponsors & Collaborators

• Threshold Pharmaceuticals: lead

Study Sites (11)

Mayo Clinic Cancer Center

Scottsdale, Arizona, 85259, United States

Location

Premiere Oncology of Arizona

Scottsdale, Arizona, 85260, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202, United States

Location

LSU Health Sciences Center

Shreveport, Louisiana, 71130, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

UT Health Science Center

San Antonio, Texas, 78229, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Borad MJ, Reddy SG, Bahary N, Uronis HE, Sigal D, Cohn AL, Schelman WR, Stephenson J Jr, Chiorean EG, Rosen PJ, Ulrich B, Dragovich T, Del Prete SA, Rarick M, Eng C, Kroll S, Ryan DP. Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer. J Clin Oncol. 2015 May 1;33(13):1475-81. doi: 10.1200/JCO.2014.55.7504. Epub 2014 Dec 15.

  PMID: 25512461 RESULT

Related Links

• Threshold Pharmaceuticals Company Website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Prostatic Neoplasms; Pancreatic Neoplasms; Hypoxia

Interventions

TH 302

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Jeffrey R Infante, MD

  SCRI Development Innovations, LLC

  PRINCIPAL INVESTIGATOR

• Mitesh Borad, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 26, 2008
• First Posted: August 28, 2008
• Study Start: August 1, 2008
• Primary Completion: July 1, 2013
• Study Completion: March 1, 2014
• Last Updated: May 7, 2015

Record last verified: 2015-05

Locations

US (11)