Rectal CancerPhase 1/2NCT01397305
An Extended Feasibility Phase I/II Study of Methylenetetrahydrofolate (Arfolitixorin) and Pemetrexed Single Agent, Given as Neoadjuvant Treatment in Patients With Resectable Rectal Cancer
A Phase 1/2 study testing [6R] 5,10-methylenetetrahydrofolate (arfolitixorin) and Pemetrexed in people with Rectal Cancer, run by Isofol Medical AB at 1 site in Sweden.
Trial summary
The purpose of this study is to determine whether an optimal dose of [6R] 5,10-methylenetetrahydrofolate (arfolitixorin) in combination with pemetrexed are effective in pre-operative treatment of patients with resectable rectal cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- [6R] 5,10-methylenetetrahydrofolate (arfolitixorin) and Pemetrexed
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteSweden
- Study dates
- 14 Apr 2011to 16 Oct 2014
- Phase
- Phase 1/2
- 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
- Pathological/ cytological diagnosis of adenocarcinoma of the rectum. Patients must have operable rectal cancer that is amenable to surgery.
- No prior therapy for rectal cancer
- Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1
- Adequate organ function
- Patient compliance and geographic proximity that allow adequate follow-up
- For women: Must be surgically sterile, postmenopausal, or compliant with a medically approved contraceptive regimen during and for 3 months after treatment; must have a negative serum or urine pregnancy test and must not be lactating.
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- For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 3 months after treatment.
- Estimated life expectancy of at least 12 weeks
- Signed informed consent
- At least 18 years of age
Who cannot join
- Concurrent administration of any other anti-tumor therapy.
- Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
- Serious concomitant systemic disorders (e.g., active infection including HIV, cardiac disease) that in the opinion of the investigator would compromise the patient's ability to complete the study.
- Have previously completed or withdrawn from this study or any other study investigating pemetrexed.
- Are pregnant or breast-feeding.
- Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
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- History of significant neurological or mental disorder, including seizures or dementia.
- Inability to interrupt aspirin or other nonsteroidal anto-inflammatory drugs (NSAIDs)
- Presence of clinically relevant third-space fluid collection that cannot be controlled by drainage or other procedures prior to study entry.
- Inability or unwillingness to be given 5,10-methylenetetrahydrofolate, vitamin B12 or dexamethasone.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Extended Feasibility Phase I/II Study of Methylenetetrahydrofolate and Pemetrexed Single Agent, Given as Neoadjuvant Treatment in Patients With Resectable Rectal Cancer
The purpose of this study is to determine whether an optimal dose of [6R] 5,10-methylenetetrahydrofolate (arfolitixorin) in combination with pemetrexed are effective in pre-operative treatment of patients with resectable rectal cancer.
- Conditions
- Rectal Cancer
- Being tested
- [6R] 5,10-methylenetetrahydrofolate (arfolitixorin), Pemetrexed
- Keywords
- 5,10-methylenetetrahydrofolate, neoadjuvant therapy, pemetrexed, Neoplasms, Rectal Neoplasms, Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Rectal Diseases, Digestive System Diseases, Gastrointestinal Diseases, Intestinal Diseases, Pharmacologic Actions, Therapeutic Uses, Antineoplastic Agents, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Folic Acid Antagonists
- Medical subject headings
- Rectal Neoplasms, Neoplasms, Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Rectal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[6R] 5,10-methylenetetrahydrofolate (arfolitixorin)Drug
Also called Modufolin, 6R-MTHF, ISO-901, arfolitixorin
10, 50, 100, 200, and 500 mg/m2 IV on day 1, day 8 day and day 15 of each 21-day cycle. 3 cycles.
PemetrexedDrug
Also called ly 231514, multitargeted antifolate
500 mg/m2 IV on day 1 of each 21-day cycle. 3 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Modufolin and Pemetrexed | Experimental | Modufolin ( [6R] 5,10-methylenetetrahydrofolate) and Pemetrexed Receives: Drug: [6R] 5,10-methylenetetrahydrofolate (arfolitixorin); Drug: Pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of Pemetrexed Prior to Surgery
Feasibility is defined as the ability to receive the total planned dose of pemetrexed (i.e., 1500 mg/m) administered over a period of no more than 9 weeks. Feasibility is measured as absence of the following toxicities:
- CTC grade 4 lasting >= 7 days, or febrile neutropenia
- CTC grade 4 thrombocytopenia or grade 3 with bleeding.
- CTC grade 3 nonhematologic toxicity (excluding nausea and vomiting, isolated CTC grade 3 ALT or AST that returns to the patient's pretreatment CTC grade within 3 weeks, or grade 3 fatigue lasting <7 days).
Measured: 3 cycles (21-day cycles)
Secondary outcomes (7)
Pathological Complete Response (pCR)
Measured: Surgery following 3 cycles (21-day cycles) of chemotherapy
Number of Participants Receiving Sphincter Saving Surgery
Measured: Surgery following 3 cycles (21-day cycles) of chemotherapy
Evaluation of qualitative and quantitative toxicities
Bleeding, anastomosis, leakage, serious infection.
Measured: Start of study treatment until last postoperative visit. Expected average 16 weeks.
[6R] 5,10-methylenetetrahydrofolate tissue concentration determination
Measured: Surgery following 3 cycles (21-day cycles) of chemotherapy
Correlation between 5,10-methylenetetrahydrofolate and HCy levels in blood
Blood samples are taken before start of study treatment, in conjunction with start of every study drug cycle, and after completed study treatment. HCy measurements performed using HPLC. 5-10-methylenetetrahydrofolate is measured in tissue biopsies (tumor and adjacent mucosa) sampled in conjunction with surgery. The tissue is collected before start of study treatment, during and after completed study treatment. 5,10-methylenetetrahydrofolate levels are measured using LC/MS/MS.
Measured: Samples taken prior before study treatment, during 3 cycles of chemotherapy and after completion of study treatment. Expected average 20 weeks.
Correlation of folate gene polymorphisms and gene signature profiling with clinical outcome and toxicity profiles.
RT-PCR will be used to measure and determine the gene expression levels of the genes FPGS (Folylpolyglutamate synthase) and GGH (Gamma-glutamyl hydrolase). This translational research will be compared with the clinical outcome and toxicity profiles of patients.
Measured: Tissue to be collected from tumor and adjacent mucosa before start of study treatment, during and after completed study treatment. Expected average 20 weeks.
Pharmacokinetic parameters of [6R] 5,10-mTHF, 5-formyl-THF, 5-methyl-THF and THF calculated from plasma
Plasma samples will be collected prior to study treatment, and at 10 minutes, 1, 2 and 4 hours after study treatment
Measured: Calculated on Day1 and Day15 after cycle 1 and 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2011 (estimated)
- Study start14 Apr 2011
- Primary completion16 Oct 2014
- Study completion16 Oct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Isofol Medical AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bengt G Gustavsson, PhD, MD, Principal investigator, Sahlgrenska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01397305
- Sponsor's protocol ID
- ISO-MC-091
- Status last verified
- Sep 2020
- First submitted
- 25 May 2011
- Last updated
- 9 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Extended Feasibility Phase I/II Study of Methylenetetrahydrofolate and Pemetrexed Single Agent, Given as Neoadjuvant Treatment in Patients With Resectable Rectal Cancer
- ClinicalTrials.gov ID
- NCT01397305
- Acronym / sponsor ID
- ISO-MC-091
- Conditions
- Rectal Cancer
- Keywords
- 5,10-methylenetetrahydrofolate, neoadjuvant therapy, pemetrexed, Neoplasms, Rectal Neoplasms, Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Isofol Medical ABIndustry (pharma, biotech, devices)
- Study start
- 14 Apr 2011 (actual)
- Primary completion
- 16 Oct 2014 (actual)
- Study completion
- 16 Oct 2014 (actual)
- First posted
- 19 Jul 2011 (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 purpose of this study is to determine whether an optimal dose of [6R] 5,10-methylenetetrahydrofolate (arfolitixorin) in combination with pemetrexed are effective in pre-operative treatment of patients with resectable rectal cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Modufolin and Pemetrexed | Experimental | Drug: [6R] 5,10-methylenetetrahydrofolate (arfolitixorin), Drug: PemetrexedModufolin ( [6R] 5,10-methylenetetrahydrofolate) and Pemetrexed |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Pathological/ cytological diagnosis of adenocarcinoma of the rectum. Patients must have operable rectal cancer that is amenable to surgery.
- No prior therapy for rectal cancer
- Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1
- Adequate organ function
- Patient compliance and geographic proximity that allow adequate follow-up
Key exclusion criteria (10 listed)
- Concurrent administration of any other anti-tumor therapy.
- Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
- Serious concomitant systemic disorders (e.g., active infection including HIV, cardiac disease) that in the opinion of the investigator would compromise the patient's ability to complete the study.
- Have previously completed or withdrawn from this study or any other study investigating pemetrexed.
- Are pregnant or breast-feeding.
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 |
|---|---|---|
| [6R] 5,10-methylenetetrahydrofolate (arfolitixorin)Also: Modufolin, 6R-MTHF, ISO-901, arfolitixorin10, 50, 100, 200, and 500 mg/m2 IV on day 1, day 8 day and day 15 of each 21-day cycle. 3 cycles. | Drug | Modufolin and Pemetrexed |
| PemetrexedAlso: ly 231514, multitargeted antifolate500 mg/m2 IV on day 1 of each 21-day cycle. 3 cycles. | Drug | Modufolin and Pemetrexed |
Primary outcome
Feasibility of Pemetrexed Prior to Surgery
Time frame: 3 cycles (21-day cycles)
Feasibility is defined as the ability to receive the total planned dose of pemetrexed (i.e., 1500 mg/m) administered over a period of no more than 9 weeks. Feasibility is measured as absence of the following toxicities: 1. CTC grade 4 lasting >= 7 days, or febrile neutropenia 2. CTC grade 4 thrombocytopenia or grade 3 with bleeding. 3. CTC grade 3 nonhematologic toxicity (excluding nausea and vomiting, isolated CTC grade 3 ALT or AST that returns to the patient's pretreatment CTC grade within 3 weeks, or grade 3 fatigue lasting <7 days).
7 secondary outcomes
Pathological Complete Response (pCR)
Time frame: Surgery following 3 cycles (21-day cycles) of chemotherapy
Number of Participants Receiving Sphincter Saving Surgery
Time frame: Surgery following 3 cycles (21-day cycles) of chemotherapy
Evaluation of qualitative and quantitative toxicities
Time frame: Start of study treatment until last postoperative visit. Expected average 16 weeks.
[6R] 5,10-methylenetetrahydrofolate tissue concentration determination
Time frame: Surgery following 3 cycles (21-day cycles) of chemotherapy
Correlation between 5,10-methylenetetrahydrofolate and HCy levels in blood
Time frame: Samples taken prior before study treatment, during 3 cycles of chemotherapy and after completion of study treatment. Expected average 20 weeks.
Correlation of folate gene polymorphisms and gene signature profiling with clinical outcome and toxicity profiles.
Time frame: Tissue to be collected from tumor and adjacent mucosa before start of study treatment, during and after completed study treatment. Expected average 20 weeks.
Pharmacokinetic parameters of [6R] 5,10-mTHF, 5-formyl-THF, 5-methyl-THF and THF calculated from plasma
Time frame: Calculated on Day1 and Day15 after cycle 1 and 3
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 9 Sep 2020.
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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.
Bengt G Gustavsson, PhD, MD principal investigator
Sahlgrenska University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing [6R] 5,10-methylenetetrahydrofolate (arfolitixorin) and Pemetrexed in people with Rectal Cancer, run by Isofol Medical AB at 1 site in Sweden.
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 10 inclusion and 10 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 9 Sep 2020. 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 Sweden. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Feasibility of Pemetrexed Prior to Surgery (time frame: 3 cycles (21-day cycles)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Sep 2020.