Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT01206465

Pralatrexate and Fluorouracil in Treating Patients With Recurrent Solid Tumors

A Phase 1 study testing pralatrexate, fluorouracil and laboratory biomarker analysis in people with Unspecified Adult Solid Tumor, Protocol Specific, run by University of Nebraska at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

RATIONALE: Pralatrexate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study

Who is it for?: Ages 19 years and older
Conditions the study is for: Unspecified Adult Solid Tumor, Protocol Specific
What is being tested?: pralatrexate, fluorouracil and laboratory biomarker analysis
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 29 participants
Where: 1 siteUnited States
Study dates: 14 Sep 2010to 1 Jun 2017
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 19 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Cancer patients who have failed standard therapy for their disease or for whom no such therapy is available are eligible, for which 5-fluoropyrimdines, including 5-FU, or inhibitors of DHFR (dihydrofolate reductase), including pralatrexate, have the potential for therapeutic benefit
Objectively measurable disease is preferred, but not required
Performance status of 0-2 (Eastern Cooperative Oncology Group [ECOG])
Prior treatment:
The patient should have recovered from the toxicities associated with prior chemotherapy (at least 3 weeks from prior therapy)
At least two or more weeks should have elapsed since any radiotherapy, and the patient should have recovered from the toxicity associated with such therapy

Show all 12Show fewer

If a recent surgical procedure has been performed, the patient should have recovered from the surgery prior to entering this trial
Absolute granulocyte count of 1500 per mcL or greater
Platelet count of 100,000 per mcL or greater
Serum bilirubin less than 1.5 times the upper limits of the institutional normal
Serum creatinine less than the upper limits of normal
The patient must willingly give signed informed consent

Who cannot join

Pregnant women and nursing mothers are ineligible; eligible patients of reproductive potential should use adequate contraception if sexually active
Serious concurrent medical illness which would jeopardize the ability of the patient to receive the chemotherapy program outlined in this protocol with reasonable safety
Patients with active infections requiring intravenous antibiotic therapy are not eligible until the infection has resolved
Patients who are human immunodeficiency virus (HIV) antibody positive and are receiving highly active antiretroviral therapy (HAART) are ineligible
Concomitant administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and trimethoprim/sulfamethoxazole will not be allowed

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Nebraska Medical Center, Eppley Cancer Center
Omaha, Nebraska, 68198-6805

Other trials in United States

About this study

Official title: A Phase I Clinical Trial of Sequential Pralatrexate Followed by a 48-hour Infusion of 5- Fluorouracil Given Every Other Week in Adult Patients With Solid Tumors

PURPOSE: This phase I trial is studying the side effects and best dose of pralatrexate when given together with fluorouracil in treating patients with recurrent solid tumors

Read the detailed description

PRIMARY OBJECTIVES:

To determine the recommended dose of PDX (pralatrexate) given in combination with a fixed dose of 5-FU (fluorouracil) administered as a 48-hour infusion given every other week.

SECONDARY OBJECTIVES:

To assess clinical response to therapy in subjects with measurable disease and time to disease progression in all subjects.

II. To assess the toxicity profile of the combination of PDX and 5-FU. III. To determine the pharmacokinetics of PDX and 5-FU and correlate with clinical toxicity.

IV. To analyze polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase (TS) and correlate with clinical toxicity.

OUTLINE: This is a dose-escalation study of pralatrexate.

Patients receive pralatrexate intravenously (IV) over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Being tested: pralatrexate, fluorouracil, laboratory biomarker analysis, DNA analysis, high performance liquid chromatography

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

pralatrexateDrug
Also called FOLOTYN, PDX
Given IV
fluorouracilDrug
Also called 5-fluorouracil, 5-Fluracil, 5-FU
Given IV
laboratory biomarker analysisOther
Correlative studies
DNA analysisGenetic
Correlative studies
high performance liquid chromatographyOther
Also called HPLC
Correlative studies
polymerase chain reactionGenetic
Also called PCR
Correlative studies
nucleic acid sequencingGenetic
Also called Gene Sequencing, Molecular Biology, Nucleic Acid Sequencing
Correlative studies
pharmacological studyOther
Also called pharmacological studies
Correlative studies
pharmacogenomic studiesOther
Also called Pharmacogenomic Study
Correlative studies
polymorphism analysisGenetic
Correlative studies

Study groups in NCT01206465
Study group	Role	What they receive
Treatment (enzyme inhibitor therapy)	Experimental	Patients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: pralatrexate; Drug: fluorouracil; Other: laboratory biomarker analysis; Genetic: DNA analysis; Other: high performance liquid chromatography; Genetic: polymerase chain reaction; Genetic: nucleic acid sequencing; Other: pharmacological study; Other: pharmacogenomic studies; Genetic: polymorphism analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

Recommended Dose of PDX Given With a Fixed Dose of 5-FU
Recommended dose of PDX given in combination with a fixed dose of 5-FU administered as a 48-hour infusion given every other weekMaximum tolerated dose will have been exceeded when 2 patients entered at a given dose level experience specified dose-limiting toxicities in the initial cycle
Measured: During the initial course (day 1 & 15 of a 4 week schedule)

Secondary outcomes (6)

Response to Therapy in Subjects With Measurable Disease
Number of Participants With Response to Therapy in Subjects With Measurable Disease
Measured: restaging imaging done after each two 4-week course until time of progression (the maximum duration of PFS = 588 days)
Number of Patients Experiencing Grade 3-4 Toxicity While Receiving the Combination of PDX and 5-FU
Participants remained on study as long as they did not progress, and wished to continue on study (no limit on number of cycles)
Measured: ., "From the time the subject signs the consent form and ending 4 weeks following the final chemotherapy, an average of 3 years
Pharmacokinetics of PDX- AUClast
Plasma concentrations versus time (at all time points)
Measured: Pre-treatment, end of infusion, at 15, 30, and 60 min, and then at 2, 4, 6, 8, 12, 22, 23, 24, 45, and 46 hours for PDX.
Polymorphisms in Methylenetetrahydrofolate Reductase and Thymidylate Synthase
Number of Participants with Polymorphisms in Methylenetetrahydrofolate Reductase and Thymidylate Synthase
Measured: Prior to the first dose of protocol therapy
5-FU Plasma Levels
Pharmacokinetics of 5-FU - Cmax plasma levels
Measured: 22, 23, 45 & 46 hours during the 48 hour infusion
Time to Disease Progression
Time to disease progression in all Participants
Measured: restaging imaging done after each two 4-week course until time of progression (longest time to progression = 588 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Sep 20101 Jun 2017

First posted21 Sep 2010 (estimated)
Study start14 Sep 2010
Primary completion4 Feb 2015
Study completion1 Jun 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Unspecified Adult Solid Tumor, Protocol SpecificStudies of the same condition, open and under way.
More trials run by University of NebraskaThe 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01206465
Sponsor's protocol ID: 0238-10-FB
Other IDs: NCI-14191
Status last verified: Dec 2023
First submitted: 17 Sep 2010
Last updated: 26 Dec 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Grem JL, Kos ME, Evande RE, Meza JL, Schwarz JK. A phase 1 clinical trial of sequential pralatrexate followed by a 48-hour infusion of 5-fluorouracil given every other week in adult patients with solid tumors. Cancer. 2015 Nov 1;121(21):3862-8. doi: 10.1002/cncr.29504. Epub 2015 Aug 4.
PubMed 26242208

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Unspecified Adult Solid Tumor, Protocol Specific trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I Clinical Trial of Sequential Pralatrexate Followed by a 48-hour Infusion of 5- Fluorouracil Given Every Other Week in Adult Patients With Solid Tumors
ClinicalTrials.gov ID: NCT01206465
Acronym / sponsor ID: 0238-10-FB
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 29 participants (actual)
Lead sponsor: University of NebraskaUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: 14 Sep 2010 (actual)
Primary completion: 4 Feb 2015 (actual)
Study completion: 1 Jun 2017 (actual)
First posted: 21 Sep 2010 (estimated)
Results: Posted 16 Jul 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

PURPOSE: This phase I trial is studying the side effects and best dose of pralatrexate when given together with fluorouracil in treating patients with recurrent solid tumors

Detailed description

PRIMARY OBJECTIVES:

To determine the recommended dose of PDX (pralatrexate) given in combination with a fixed dose of 5-FU (fluorouracil) administered as a 48-hour infusion given every other week.

SECONDARY OBJECTIVES:

To assess clinical response to therapy in subjects with measurable disease and time to disease progression in all subjects.

II. To assess the toxicity profile of the combination of PDX and 5-FU. III. To determine the pharmacokinetics of PDX and 5-FU and correlate with clinical toxicity.

IV. To analyze polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase (TS) and correlate with clinical toxicity.

OUTLINE: This is a dose-escalation study of pralatrexate.

After completion of study treatment, patients are followed up for 30 days.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (enzyme inhibitor therapy)	Experimental	Drug: pralatrexate, Drug: fluorouracil, Other: laboratory biomarker analysis, Genetic: DNA analysis, Other: high performance liquid chromatography, Genetic: polymerase chain reaction, Genetic: nucleic acid sequencing, Other: pharmacological study, Other: pharmacogenomic studies, Genetic: polymorphism analysisPatients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who may qualify

Ages: 19 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Cancer patients who have failed standard therapy for their disease or for whom no such therapy is available are eligible, for which 5-fluoropyrimdines, including 5-FU, or inhibitors of DHFR (dihydrofolate reductase), including pralatrexate, have the potential for therapeutic benefit
Objectively measurable disease is preferred, but not required
Performance status of 0-2 (Eastern Cooperative Oncology Group [ECOG])
Prior treatment:
The patient should have recovered from the toxicities associated with prior chemotherapy (at least 3 weeks from prior therapy)

Key exclusion criteria (5 listed)

Pregnant women and nursing mothers are ineligible; eligible patients of reproductive potential should use adequate contraception if sexually active
Serious concurrent medical illness which would jeopardize the ability of the patient to receive the chemotherapy program outlined in this protocol with reasonable safety
Patients with active infections requiring intravenous antibiotic therapy are not eligible until the infection has resolved
Patients who are human immunodeficiency virus (HIV) antibody positive and are receiving highly active antiretroviral therapy (HAART) are ineligible
Concomitant administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and trimethoprim/sulfamethoxazole will not be allowed

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
pralatrexateAlso: FOLOTYN, PDXGiven IV	Drug	Treatment (enzyme inhibitor therapy)
fluorouracilAlso: 5-fluorouracil, 5-Fluracil, 5-FUGiven IV	Drug	Treatment (enzyme inhibitor therapy)
laboratory biomarker analysisCorrelative studies	Other	Treatment (enzyme inhibitor therapy)
DNA analysisCorrelative studies	Genetic	Treatment (enzyme inhibitor therapy)
high performance liquid chromatographyAlso: HPLCCorrelative studies	Other	Treatment (enzyme inhibitor therapy)
polymerase chain reactionAlso: PCRCorrelative studies	Genetic	Treatment (enzyme inhibitor therapy)
nucleic acid sequencingAlso: Gene Sequencing, Molecular Biology, Nucleic Acid SequencingCorrelative studies	Genetic	Treatment (enzyme inhibitor therapy)
pharmacological studyAlso: pharmacological studiesCorrelative studies	Other	Treatment (enzyme inhibitor therapy)
pharmacogenomic studiesAlso: Pharmacogenomic StudyCorrelative studies	Other	Treatment (enzyme inhibitor therapy)
polymorphism analysisCorrelative studies	Genetic	Treatment (enzyme inhibitor therapy)

Primary outcome

Recommended Dose of PDX Given With a Fixed Dose of 5-FU
Time frame: During the initial course (day 1 & 15 of a 4 week schedule)
Recommended dose of PDX given in combination with a fixed dose of 5-FU administered as a 48-hour infusion given every other weekMaximum tolerated dose will have been exceeded when 2 patients entered at a given dose level experience specified dose-limiting toxicities in the initial cycle

6 secondary outcomes

Response to Therapy in Subjects With Measurable Disease
Time frame: restaging imaging done after each two 4-week course until time of progression (the maximum duration of PFS = 588 days)
Number of Patients Experiencing Grade 3-4 Toxicity While Receiving the Combination of PDX and 5-FU
Time frame: ., "From the time the subject signs the consent form and ending 4 weeks following the final chemotherapy, an average of 3 years
Pharmacokinetics of PDX- AUClast
Time frame: Pre-treatment, end of infusion, at 15, 30, and 60 min, and then at 2, 4, 6, 8, 12, 22, 23, 24, 45, and 46 hours for PDX.
Polymorphisms in Methylenetetrahydrofolate Reductase and Thymidylate Synthase
Time frame: Prior to the first dose of protocol therapy
5-FU Plasma Levels
Time frame: 22, 23, 45 & 46 hours during the 48 hour infusion
Time to Disease Progression
Time frame: restaging imaging done after each two 4-week course until time of progression (longest time to progression = 588 days)

Results and safety

Results posted to the registry on 16 Jul 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
75 mg/m^2	3	3
94 mg/m^2	6	6
118 mg/m^2	6	6
148 mg/m^2	6	6
185 mg/m^2	6	6

Primary outcome: Recommended Dose of PDX Given With a Fixed Dose of 5-FU

Time frame: During the initial course (day 1 & 15 of a 4 week schedule). Number. Unit: mg per meter square

Measure	Treatment (Enzyme Inhibitor Therapy) n = 27
Value	148

Population analysed: All participants receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data is collected on participants from the time of consent until 30 days after the participant is off study drug.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment (Enzyme Inhibitor Therapy)	10 of 27 (37%)	27 of 27 (100%)	3 of 27

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 26242208Grem JL, Kos ME, Evande RE, Meza JL, Schwarz JK. A phase 1 clinical trial of sequential pralatrexate followed by a 48-hour infusion of 5-fluorouracil given every other week in adult patients with solid tumors. Cancer. 2015 Nov 1;121(21):3862-8. doi: 10.1002/cncr.29504. Epub 2015 Aug 4.

Related trials for Unspecified Adult Solid Tumor, Protocol Specific

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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.

Jean Grem principal investigator

University of Nebraska

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 12 inclusion and 5 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 26 Dec 2023. 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?

Yes. Results are posted in the registry (first posted 16 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Recommended Dose of PDX Given With a Fixed Dose of 5-FU (time frame: During the initial course (day 1 & 15 of a 4 week schedule)). 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 NCT01206465, 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 26 Dec 2023.