NeoplasmsPhase 1NCT01240577
An Early Phase I Study of IPdR Absorption, Metabolism, and Safety in Patients With Advanced Solid Tumors and Lymphomas
A Phase 1 study testing IPdR in people with Neoplasms and Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: The experimental drug IPdR is broken down in the body to IdUrd, which has been given to patients to find out if it can improve radiation therapy. IdUrd has to be given through a vein; therefore this new drug (IPdR) has been made which can be taken by mouth. Read more about this study
- Who is it for?
- Ages 18 to 110 years
- What is being tested?
- IPdR
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Oct 2010to 30 Jul 2012
- 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 to 110 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically documented (confirmed at the Laboratory of Pathology, NCI) solid tumors or lymphoid malignancies that are refractory to at least one line of standard treatment or for which no standard therapy is available. Patients with lymphoid malignancies may be enrolled if they have disease for which standard therapy is currently not indicated. Patients should not have disease-associated symptoms requiring immediate therapy or intervention.
- Any prior chemotherapy or radiation therapy must have been completed greater than or equal to 2 weeks prior to enrollment (6 weeks for nitrosoureas or mitomycin C), and the patient must have recovered to eligibility levels from prior toxicity.
- Age greater than or equal to 18 years. Patients under 18 years of age are excluded because of their inability as a protected population to give appropriate consent to this non-therapeutic study.
- ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).
- Life expectancy of at least 3 months.
- Patients must have normal organ and marrow function as defined below:
Show all 16Show fewer
- absolute neutrophil count greater than or equal to 1,500/microL
- platelets greater than or equal to 100,000/microL
- total bilirubin less than 1.5 times institutional upper limit of normal (ULN)
- AST(SGOT)/ALT(SGPT) less than or equal to 3.0 times ULN
- creatinine less than 1.5 times ULN
- OR:
- --creatinine clearance greater than or equal to 60 mL/min for patients with creatinine levels greater than or equal to 1.5 times ULN
- IPdR is a nucleoside analog and therefore potentially teratogenic. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 30 days after study drug administration. Because there is an unknown but potential risk for adverse events in nursing infants secondary to IPdR administration to the mother, nursing mothers should not receive IPdR.
- Ability to understand and the willingness to sign a written informed consent document.
- -Both men and women and members of all races and ethnic groups are eligible for this trial.
Who cannot join
- Patients may not be receiving any other investigational agents.
- Uncontrolled intercurrent illness including, but not limited to, ongoing uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, GI conditions limiting absorption, serious skin conditions, or psychiatric illness/social situations that would limit compliance with study requirements.
- Women who are pregnant or nursing.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Background:
- The experimental drug IPdR is broken down in the body to IdUrd, which has been given to patients to find out if it can improve radiation therapy. IdUrd has to be given through a vein; therefore this new drug (IPdR) has been made which can be taken by mouth. Researchers are interested in determining whether IPdR should also be studied to find out if it can improve radiation therapy. The current study is to find out if people absorb the drug given by mouth.
Read more
Objectives:
- To evaluate the levels of drug and its breakdown products in the blood following a single dose of IPdR by mouth. .
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with cancer (solid tumors or lymphomas) that have not responded to standard treatment.
Design:
- This study involves an initial dosing visit, one day of admission to the hospital for blood work, and a follow-up visit 14 days later.
- Participants will be screened with a physical examination and medical history, as well as blood and urine samples.
- Participants will receive a single dose of IPdR, and will provide multiple blood and urine samples for 24 hours after administration of the drug.
- Fourteen days after receiving IPdR, participants will have another physical examination and additional blood and urine tests to evaluate how IPdR has been broken down by the body.
- Cancer treatment will not be provided as part of this protocol.
Read the detailed description
Background:
- The nucleoside analog iododeoxyuridine (IdUrd, NSC 39661) has shown promising activity as a radiosensitizer in preclinical models and has been evaluated in Phase I/II clinical trials. The extent of radiosensitization is directly related to the incorporation of IdUrd into tumor DNA as a replacement for thymidine.
- IPdR (NSC 726188) is an orally administered prodrug of IdUrd with a better therapeutic index in preclinical models.
- This first in human study of IPdR will evaluate whether IPdR is absorbed and what plasma levels of IPdR and its major metabolite, IdUrd, are achieved after a single oral dose.
Objectives:
- Measure plasma concentrations of IPdR, IdUrd, and IdUrd metabolites after a single oral dose of IPdR
- Determine the safety of administering a single oral dose of IPdR.
Eligibility:
-Patients must be greater than or equal to 18 years of age and have histologically confirmed solid tumors or lymphoid malignancies refractory to at least one line of standard treatment or for which no standard therapy is available. Patients should have adequate organ function and no disease-associated symptoms requiring immediate therapy or intervention.
Study Design:
- Patients will receive a single oral dose of IPdR on day 1.
- The initial IPdR dose will be 150 mg; dose escalation will be in 100% increments to a maximum of 2400 mg. One patient will be accrued to each dose level until we reach the highest dose level. Six patients will be accrued at dose level 5 (2400 mg).
- Being tested
- IPdR
- Keywords
- IPdR, Pharmacokinetics, Early Phase I, Cancer, Solid Tumor, Lymphoma
- Medical subject headings
- Neoplasms, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IPdRDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
-Measure plasma concentrations of IPdR, IdUrd, and IdUrd metabolites after a single oral dose of IPdR.-Determine the safety of administering a single oral dose of IPdR.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2010 (estimated)
- Study start26 Oct 2010
- Primary completion30 Jul 2012
- Study completion30 Jul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Investigators
- Shivaani Kummar, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01240577
- Sponsor's protocol ID
- 110026
- Other IDs
- 11-C-0026
- Status last verified
- 26 Feb 2013
- First submitted
- 11 Nov 2010
- Last updated
- 18 Oct 2018
- Results posted
- No
Publications
Schulz CA, Mehta MP, Badie B, McGinn CJ, Robins HI, Hayes L, Chappell R, Volkman J, Binger K, Arzoomanian R, Simon K, Alberti D, Feierabend C, Tutsch KD, Kunugi KA, Wilding G, Kinsella TJ. Continuous 28-day iododeoxyuridine infusion and hyperfractionated accelerated radiotherapy for malignant glioma: a phase I clinical study. Int J Radiat Oncol Biol Phys. 2004 Jul 15;59(4):1107-15. doi: 10.1016/j.ijrobp.2003.12.007.
PubMed 15234045Saif MW, Berk G, Cheng YC, Kinsella TJ. IPdR: a novel oral radiosensitizer. Expert Opin Investig Drugs. 2007 Sep;16(9):1415-24. doi: 10.1517/13543784.16.9.1415.
PubMed 17714027Kinsella TJ. An approach to the radiosensitization of human tumors. Cancer J Sci Am. 1996 Jul-Aug;2(4):184-93.
PubMed 9166528
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Early Phase I Study of IPdR Absorption, Metabolism, and Safety in Patients With Advanced Solid Tumors and Lymphomas
- ClinicalTrials.gov ID
- NCT01240577
- Acronym / sponsor ID
- 110026
- Keywords
- IPdR, Pharmacokinetics, Early Phase I, Cancer, Solid Tumor, Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 26 Oct 2010
- Primary completion
- 30 Jul 2012 (actual)
- Study completion
- 30 Jul 2012 (actual)
- First posted
- 15 Nov 2010 (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.
Background:
- The experimental drug IPdR is broken down in the body to IdUrd, which has been given to patients to find out if it can improve radiation therapy. IdUrd has to be given through a vein; therefore this new drug (IPdR) has been made which can be taken by mouth. Researchers are interested in determining whether IPdR should also be studied to find out if it can improve radiation therapy. The current study is to find out if people absorb the drug given by mouth.
Objectives:
- To evaluate the levels of drug and its breakdown products in the blood following a single dose of IPdR by mouth. .
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with cancer (solid tumors or lymphomas) that have not responded to standard treatment.
Design:
- This study involves an initial dosing visit, one day of admission to the hospital for blood work, and a follow-up visit 14 days later.
- Participants will be screened with a physical examination and medical history, as well as blood and urine samples.
- Participants will receive a single dose of IPdR, and will provide multiple blood and urine samples for 24 hours after administration of the drug.
- Fourteen days after receiving IPdR, participants will have another physical examination and additional blood and urine tests to evaluate how IPdR has been broken down by the body.
- Cancer treatment will not be provided as part of this protocol.
Detailed description
Background:
- The nucleoside analog iododeoxyuridine (IdUrd, NSC 39661) has shown promising activity as a radiosensitizer in preclinical models and has been evaluated in Phase I/II clinical trials. The extent of radiosensitization is directly related to the incorporation of IdUrd into tumor DNA as a replacement for thymidine.
- IPdR (NSC 726188) is an orally administered prodrug of IdUrd with a better therapeutic index in preclinical models.
- This first in human study of IPdR will evaluate whether IPdR is absorbed and what plasma levels of IPdR and its major metabolite, IdUrd, are achieved after a single oral dose.
Objectives:
- Measure plasma concentrations of IPdR, IdUrd, and IdUrd metabolites after a single oral dose of IPdR
- Determine the safety of administering a single oral dose of IPdR.
Eligibility:
-Patients must be greater than or equal to 18 years of age and have histologically confirmed solid tumors or lymphoid malignancies refractory to at least one line of standard treatment or for which no standard therapy is available. Patients should have adequate organ function and no disease-associated symptoms requiring immediate therapy or intervention.
Study Design:
- Patients will receive a single oral dose of IPdR on day 1.
- The initial IPdR dose will be 150 mg; dose escalation will be in 100% increments to a maximum of 2400 mg. One patient will be accrued to each dose level until we reach the highest dose level. Six patients will be accrued at dose level 5 (2400 mg).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 110 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients must have histologically documented (confirmed at the Laboratory of Pathology, NCI) solid tumors or lymphoid malignancies that are refractory to at least one line of standard treatment or for which no standard therapy is available. Patients with lymphoid malignancies may be enrolled if they have disease for which standard therapy is currently not indicated. Patients should not have disease-associated symptoms requiring immediate therapy or intervention.
- Any prior chemotherapy or radiation therapy must have been completed greater than or equal to 2 weeks prior to enrollment (6 weeks for nitrosoureas or mitomycin C), and the patient must have recovered to eligibility levels from prior toxicity.
- Age greater than or equal to 18 years. Patients under 18 years of age are excluded because of their inability as a protected population to give appropriate consent to this non-therapeutic study.
- ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).
- Life expectancy of at least 3 months.
Key exclusion criteria (3 listed)
- Patients may not be receiving any other investigational agents.
- Uncontrolled intercurrent illness including, but not limited to, ongoing uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, GI conditions limiting absorption, serious skin conditions, or psychiatric illness/social situations that would limit compliance with study requirements.
- Women who are pregnant or nursing.
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 |
|---|---|---|
| IPdR | Drug | – |
Primary outcome
-Measure plasma concentrations of IPdR, IdUrd, and IdUrd metabolites after a single oral dose of IPdR.-Determine the safety of administering a single oral dose of IPdR.
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 18 Oct 2018.
- Background: PubMed 15234045Schulz CA, Mehta MP, Badie B, McGinn CJ, Robins HI, Hayes L, Chappell R, Volkman J, Binger K, Arzoomanian R, Simon K, Alberti D, Feierabend C, Tutsch KD, Kunugi KA, Wilding G, Kinsella TJ. Continuous 28-day iododeoxyuridine infusion and hyperfractionated accelerated radiotherapy for malignant glioma: a phase I clinical study. Int J Radiat Oncol Biol Phys. 2004 Jul 15;59(4):1107-15. doi: 10.1016/j.ijrobp.2003.12.007.
- Background: PubMed 17714027Saif MW, Berk G, Cheng YC, Kinsella TJ. IPdR: a novel oral radiosensitizer. Expert Opin Investig Drugs. 2007 Sep;16(9):1415-24. doi: 10.1517/13543784.16.9.1415.
- Background: PubMed 9166528Kinsella TJ. An approach to the radiosensitization of human tumors. Cancer J Sci Am. 1996 Jul-Aug;2(4):184-93.
Related trials for Neoplasms
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
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.
Shivaani Kummar, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IPdR in people with Neoplasms and Lymphoma, run by National Cancer Institute (NCI) at 1 site 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 16 inclusion and 3 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 18 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
-Measure plasma concentrations of IPdR, IdUrd, and IdUrd metabolites after a single oral dose of IPdR.-Determine the safety of administering a single oral dose of IPdR.. 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 NCT01240577, which also lists 3 linked publications.
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 18 Oct 2018.