Lung CancerPhase 1NCT00096707
Dose Escalation Trial of 2-Deoxy-D-Glucose (2DG) in Subjects With Advanced Solid Tumors
A Phase 1 study testing 2-deoxy-D-glucose (2DG) in people with Lung Cancer and Breast Cancer, run by Threshold Pharmaceuticals at 3 sites in United States.
Trial summary
The objectives of this study are to evaluate the safety, tolerability, pharmacokinetics, and biologic effect (FDG PET, preliminary efficacy) of daily oral doses of 2DG with and without weekly docetaxel in subjects with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer, Breast Cancer, Pancreatic Cancer
- What is being tested?
- 2-deoxy-D-glucose (2DG)
- How many people
- 50 participants
- Where
- 3 sitesUnited States
- Study dates
- Feb 2004to Jul 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females, at least 18 years of age
- Histologically confirmed, locally advanced or metastatic solid malignancy
- Previously treated with at least one chemotherapy regimen for advanced or metastatic disease OR no curative standard treatment is available
- Recovered from reversible toxicities of prior therapy
- Life expectancy of at least 3 months
- ECOG performance status of 0, 1, or 2
Show all 9Show fewer
- Measurable or nonmeasurable disease by RECIST criteria
- Ability to understand the purposes and risks of the study and having signed a written informed consent form
- All women of childbearing potential and all men must agree to use effective means of contraception from entry into the study through 3 months after the last dose
Who cannot join
- Previous or current CNS metastases (screening CT or MRI is not required in asymptomatic subjects)
- Active clinically significant infection requiring antibiotics
- Known glucose-6-phosphate dehydrogenase deficiency or history of anemia of unknown etiology
- History of clinically significant unexplained episodes of hypotension, fainting, dizziness, or lightheadedness
- History or symptoms of cardiovascular disease, particularly coronary artery disease, arrhythmias, or conduction defects with risk of cardiovascular instability, uncontrolled hypertension, clinically significant pericardial effusion, or congestive heart failure
- History of transient ischemic attack, stroke, or seizure disorder or any other CNS disease considered to be significant by the investigator
Show all 30Show fewer
- Known autonomic dysfunction or chronic orthostatic hypotension
- Evidence of hypoglycemia, clinically significant renal disease, clinically significant liver disease (other than liver metastases), diabetes mellitus, gastrointestinal disorder (that could affect absorption or elimination of orally-administered medications), or obstructive uropathy with significant post-void residual during the past 5 years
- Known HIV infection
- Other primary malignancies (other than treated basal cell carcinoma of the skin or treated in situ cervical cancer) within the past 5 years
- Major surgery within 4 weeks of the start of study treatment, without complete recovery
- Antitumor therapy within 21 days of the start of study treatment
- Disease progression/relapse on docetaxel therapy within the past 12 months
- A history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
- Known sensitivity to methylparaben or propylparaben
- Inability to discontinue prohibited medications for 24 hours before and after dosing on Day 1 of Weeks 1, 2, and 3 and Day 5 of Week 1. In addition, patients who cannot discontinue medications known to induce or inhibit CYP 3A4, such as cyclosporine, terfenadine, ketoconazole, erythromycin, and troleandomycin, for the duration of the study are not eligible.
- Peripheral neuropathy >= Grade 2
- Hemoglobin <9 g/dL
- ANC <1500/μL
- Platelet count <100,000/μL
- Total bilirubin >1.5 mg/dL
- Abnormal liver function
- Serum creatinine >1.5 mg/dL unless creatinine clearance is >= 60 mL/min
- Serum potassium < lower limit of normal
- Elevated fasting blood glucose
- Pregnant or nursing women
- Participation in an investigational drug or device study within 28 days of the first day of dosing on this study
- 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 other reason
- Subjects who live alone
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Indiana University Cancer Center
Indianapolis, Indiana, 46202
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Institute for Drug Development Cancer Therapy & Research Center
San Antonio, Texas, 78229
About this study
Official title: Phase I Dose Escalation Trial of 2-Deoxy-D-Glucose (2DG) Alone and in Combination With Docetaxel in Subjects With Advanced Solid Malignancies
The objectives of this study are to evaluate the safety, tolerability, pharmacokinetics, and biologic effect (FDG PET, preliminary efficacy) of daily oral doses of 2DG with and without weekly docetaxel in subjects with advanced solid tumors.
Read the detailed description
2-deoxy-D-glucose (2DG) is a synthetic glucose analog under development by Threshold Pharmaceuticals, Inc. that exploits the differences in metabolism between normal and malignant cells. Malignant cells utilize glucose at a much higher rate than normal cells and are therefore more dependent on aerobic and anaerobic glycolysis. If glycolysis could be blocked preferentially in malignant cells, 2DG would have potential for anti-tumor therapy. Hypoxic cells are especially dependent on anaerobic glycolysis and are generally resistant to anti-tumor therapies such as chemotherapy and radiotherapy. Therefore, combining 2DG with chemotherapy may be a way to simultaneously target both hypoxic and aerobic cells in tumors.
Four factors may play a role in the preferential toxicity of 2DG in malignant cells: (1) increased uptake and retention of glucose analogs by malignant cells; (2) relative hypoxia of tumor cells relative to normal cells; (3) malignant cells may be more sensitive to glucose deprivation than normal cells; and (4) inhibition of glycolysis may increase sensitivity to some cytotoxic agents. Preliminary data in human tumor xenografts support this hypothesis.
Because 2DG is most likely to be effective in combination with chemotherapy, this trial was designed to evaluate the maximum tolerated dose (MTD) of 2DG both alone and in combination with chemotherapy. Docetaxel was chosen because there is evidence in human tumor xenografts of delayed tumor growth for 2DG in combination with paclitaxel compared to paclitaxel alone and it has been reported that taxanes may enhance uptake of 2DG into malignant cells. Patients with advanced solid tumors were chosen because they are appropriate candidates for a Phase I clinical trial and because their tumors are likely to have areas of hypoxia.
- Being tested
- 2-deoxy-D-glucose (2DG)
- Keywords
- advanced solid tumors, cancer, docetaxel, 2-deoxy-D-glucose (2DG), phase 1
- Medical subject headings
- Lung Neoplasms, Breast Neoplasms, Pancreatic Neoplasms, Head and Neck Neoplasms, Stomach Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
2-deoxy-D-glucose (2DG)Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
Significant Toxicity
Disease Progression
Secondary outcomes (2)
Response Rate
Death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2004 (estimated)
- Study startFeb 2004
- Primary completionJul 2008
- Study completionJul 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Threshold Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Luis Raez, MD, Principal investigator, University of Miami Sylvester Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00096707
- Sponsor's protocol ID
- TH-CR-101
- Status last verified
- Apr 2009
- First submitted
- 12 Nov 2004
- Last updated
- 29 Apr 2009
- Results posted
- No
Publications
Raez LE, Papadopoulos K, Ricart AD, Chiorean EG, Dipaola RS, Stein MN, Rocha Lima CM, Schlesselman JJ, Tolba K, Langmuir VK, Kroll S, Jung DT, Kurtoglu M, Rosenblatt J, Lampidis TJ. A phase I dose-escalation trial of 2-deoxy-D-glucose alone or combined with docetaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013 Feb;71(2):523-30. doi: 10.1007/s00280-012-2045-1. Epub 2012 Dec 11.
PubMed 23228990
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Escalation Trial of 2-Deoxy-D-Glucose (2DG) Alone and in Combination With Docetaxel in Subjects With Advanced Solid Malignancies
- ClinicalTrials.gov ID
- NCT00096707
- Acronym / sponsor ID
- TH-CR-101
- Keywords
- advanced solid tumors, cancer, docetaxel, 2-deoxy-D-glucose (2DG), phase 1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Threshold PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Feb 2004
- Primary completion
- Jul 2008 (actual)
- Study completion
- Jul 2008 (actual)
- First posted
- 15 Nov 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objectives of this study are to evaluate the safety, tolerability, pharmacokinetics, and biologic effect (FDG PET, preliminary efficacy) of daily oral doses of 2DG with and without weekly docetaxel in subjects with advanced solid tumors.
Detailed description
2-deoxy-D-glucose (2DG) is a synthetic glucose analog under development by Threshold Pharmaceuticals, Inc. that exploits the differences in metabolism between normal and malignant cells. Malignant cells utilize glucose at a much higher rate than normal cells and are therefore more dependent on aerobic and anaerobic glycolysis. If glycolysis could be blocked preferentially in malignant cells, 2DG would have potential for anti-tumor therapy. Hypoxic cells are especially dependent on anaerobic glycolysis and are generally resistant to anti-tumor therapies such as chemotherapy and radiotherapy. Therefore, combining 2DG with chemotherapy may be a way to simultaneously target both hypoxic and aerobic cells in tumors.
Four factors may play a role in the preferential toxicity of 2DG in malignant cells: (1) increased uptake and retention of glucose analogs by malignant cells; (2) relative hypoxia of tumor cells relative to normal cells; (3) malignant cells may be more sensitive to glucose deprivation than normal cells; and (4) inhibition of glycolysis may increase sensitivity to some cytotoxic agents. Preliminary data in human tumor xenografts support this hypothesis.
Because 2DG is most likely to be effective in combination with chemotherapy, this trial was designed to evaluate the maximum tolerated dose (MTD) of 2DG both alone and in combination with chemotherapy. Docetaxel was chosen because there is evidence in human tumor xenografts of delayed tumor growth for 2DG in combination with paclitaxel compared to paclitaxel alone and it has been reported that taxanes may enhance uptake of 2DG into malignant cells. Patients with advanced solid tumors were chosen because they are appropriate candidates for a Phase I clinical trial and because their tumors are likely to have areas of hypoxia.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Males and females, at least 18 years of age
- Histologically confirmed, locally advanced or metastatic solid malignancy
- Previously treated with at least one chemotherapy regimen for advanced or metastatic disease OR no curative standard treatment is available
- Recovered from reversible toxicities of prior therapy
- Life expectancy of at least 3 months
Key exclusion criteria (30 listed)
- Previous or current CNS metastases (screening CT or MRI is not required in asymptomatic subjects)
- Active clinically significant infection requiring antibiotics
- Known glucose-6-phosphate dehydrogenase deficiency or history of anemia of unknown etiology
- History of clinically significant unexplained episodes of hypotension, fainting, dizziness, or lightheadedness
- History or symptoms of cardiovascular disease, particularly coronary artery disease, arrhythmias, or conduction defects with risk of cardiovascular instability, uncontrolled hypertension, clinically significant pericardial effusion, or congestive heart failure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 2-deoxy-D-glucose (2DG) | Drug | – |
Primary outcome
Significant Toxicity
Disease Progression
2 secondary outcomes
Response Rate
Death
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2009.
- Derived from this study: PubMed 23228990Raez LE, Papadopoulos K, Ricart AD, Chiorean EG, Dipaola RS, Stein MN, Rocha Lima CM, Schlesselman JJ, Tolba K, Langmuir VK, Kroll S, Jung DT, Kurtoglu M, Rosenblatt J, Lampidis TJ. A phase I dose-escalation trial of 2-deoxy-D-glucose alone or combined with docetaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013 Feb;71(2):523-30. doi: 10.1007/s00280-012-2045-1. Epub 2012 Dec 11.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luis Raez, MD principal investigator
University of Miami Sylvester Comprehensive Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 2-deoxy-D-glucose (2DG) in people with Lung Cancer and Breast Cancer, run by Threshold Pharmaceuticals at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Apr 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Significant Toxicity. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00096707, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2009.