Clinical trial NCT01397305: An Extended Feasibility Phase I/II Study of Methylenetetrahydrofolate (Arfolitixorin) and Pemetrexed Single Agent, Given as Neoadjuvant Treatment in Patients With Resectable Rectal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Rectal Cancer
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
Antimetabolites, Antineoplastic
Antimetabolites
Lead sponsor: Isofol Medical AB
Sponsor class: INDUSTRY
First posted: 2011-07-19
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

* 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.
* 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

Exclusion Criteria:

* 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.
* 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.

Primary outcomes:
measure: Feasibility of Pemetrexed Prior to Surgery
timeFrame: 3 cycles (21-day cycles)
Secondary outcomes:
measure: Pathological Complete Response (pCR)
timeFrame: Surgery following 3 cycles (21-day cycles) of chemotherapy
measure: Number of Participants Receiving Sphincter Saving Surgery
timeFrame: Surgery following 3 cycles (21-day cycles) of chemotherapy
measure: Evaluation of qualitative and quantitative toxicities
timeFrame: Start of study treatment until last postoperative visit. Expected average 16 weeks.
measure: [6R] 5,10-methylenetetrahydrofolate tissue concentration determination
timeFrame: Surgery following 3 cycles (21-day cycles) of chemotherapy
measure: Correlation between 5,10-methylenetetrahydrofolate and HCy levels in blood
timeFrame: Samples taken prior before study treatment, during 3 cycles of chemotherapy and after completion of study treatment. Expected average 20 weeks.
measure: Correlation of folate gene polymorphisms and gene signature profiling with clinical outcome and toxicity profiles.
timeFrame: Tissue to be collected from tumor and adjacent mucosa before start of study treatment, during and after completed study treatment. Expected average 20 weeks.
measure: Pharmacokinetic parameters of [6R] 5,10-mTHF, 5-formyl-THF, 5-methyl-THF and THF calculated from plasma
timeFrame: Calculated on Day1 and Day15 after cycle 1 and 3
Other outcomes:
Locations:
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
Study officials:
affiliation: Sahlgrenska University Hospital
name: Bengt G Gustavsson, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: