Modufolin (6R 5,10-Methylenetetrahydrofolate) and Pemetrexed for Neoadjuvant Rectal Cancer Treatment
This study is currently recruiting participants.
Verified July 2011 by Isofol Medical AB
Sponsor:
Isofol Medical AB
Information provided by:
Isofol Medical AB
ClinicalTrials.gov Identifier:
NCT01397305
First received: May 25, 2011
Last updated: July 18, 2011
Last verified: July 2011
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Purpose
The purpose of this study is to determine whether an optimal dose of [6R] 5,10-methylenetetrahydrofolate (Modufolin) in combination with pemetrexed are effective in pre-operative treatment of patients with resectable rectal cancer.
| Condition | Intervention | Phase |
|---|---|---|
|
Rectal Cancer |
Drug: [6R] 5,10-methylenetetrahydrofolate Drug: Pemetrexed |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Further study details as provided by Isofol Medical AB:
Primary Outcome Measures:
- Feasibility of Pemetrexed Prior to Surgery [ Time Frame: 3 cycles (21-day cycles) ] [ Designated as safety issue: Yes ]
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).
Secondary Outcome Measures:
- Pathological Complete Response (pCR) [ Time Frame: Surgery following 3 cycles (21-day cycles) of chemotherapy ] [ Designated as safety issue: No ]
- Number of Participants Receiving Sphincter Saving Surgery [ Time Frame: Surgery following 3 cycles (21-day cycles) of chemotherapy ] [ Designated as safety issue: No ]
- Evaluation of qualitative and quantitative toxicities [ Time Frame: Start of study treatment until last postoperative visit. Expected average 16 weeks. ] [ Designated as safety issue: Yes ]Bleeding, anastomosis, leakage, serious infection.
- [6R] 5,10-methylenetetrahydrofolate tissue concentration determination [ Time Frame: Surgery following 3 cycles (21-day cycles) of chemotherapy ] [ Designated as safety issue: No ]
- 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. ] [ Designated as safety issue: No ]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.
- 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. ] [ Designated as safety issue: No ]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.
| Estimated Enrollment: | 52 |
| Study Start Date: | April 2011 |
| Estimated Primary Completion Date: | July 2013 (Final data collection date for primary outcome measure) |
Intervention Details:
-
Drug: [6R] 5,10-methylenetetrahydrofolate
- Modufolin
- 6R-MTHF
- ISO-901
- ly 231514
- multitargeted antifolate
- pemetrexed
10, 50 or 100 mg/m2 IV on day 1, day 8 day and day 15 of each 21-day cycle. 3 cycles.
Other Names:
Drug: Pemetrexed
500 mg/m2 IV on day 1 of each 21-day cycle. 3 cycles.
Other Names:
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01397305
Contacts
| Contact: Anders G Rabbe | +46707646500 | anders.rabbe@isofolmedical.com |
Locations
| Sweden | |
| Sahlgrenska University Hospital | Recruiting |
| Göteborg, Sweden, 416 85 | |
| Contact: Hillevi Björkqvist, RN +46313436657 hillevi.bjorkqvist@vgregion.se | |
| Principal Investigator: Bengt Gustavsson, PhD, MD | |
Sponsors and Collaborators
Isofol Medical AB
Investigators
| Principal Investigator: | Bengt G Gustavsson, PhD, MD | Sahlgrenska University Hospital, Sweden |
More Information
No publications provided
| Responsible Party: | Isofol Medical |
| ClinicalTrials.gov Identifier: | NCT01397305 History of Changes |
| Other Study ID Numbers: | ISO-MC-091 |
| Study First Received: | May 25, 2011 |
| Last Updated: | July 18, 2011 |
| Health Authority: | Sweden: Medical Products Agency |
Keywords provided by Isofol Medical AB:
|
Digestive System Diseases Gastrointestinal Diseases 5,10-methylenetetrahydrofolate neoadjuvant therapy pemetrexed Neoplasms Rectal Neoplasms Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site |
Rectal Diseases Intestinal Diseases Pemetrexed Pharmacologic Actions Therapeutic Uses Antineoplastic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Folic Acid Antagonists Antimetabolites, Antineoplastic Antimetabolites |
Additional relevant MeSH terms:
|
Digestive System Diseases Gastrointestinal Diseases Rectal Neoplasms Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Intestinal Diseases Rectal Diseases Antimetabolites Pemetrexed |
Antimetabolites, Antineoplastic Antineoplastic Agents Folic Acid Antagonists Tetrahydrofolates Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Therapeutic Uses Enzyme Inhibitors Vitamin B Complex Vitamins Micronutrients Growth Substances Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on May 21, 2013