An Extended Feasibility Phase I/II Study of Methylenetetrahydrofolate (Arfolitixorin) and Pemetrexed Single Agent, Given as Neoadjuvant Treatment in Patients With Resectable Rectal Cancer

NCT01397305 | Completed Phase 1

• 1 other identifier: ISO-MC-091
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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: 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).

  3 cycles (21-day cycles)

Secondary Outcomes (7)

• Pathological Complete Response (pCR)

  Surgery following 3 cycles (21-day cycles) of chemotherapy

• Number of Participants Receiving Sphincter Saving Surgery

  Surgery following 3 cycles (21-day cycles) of chemotherapy

• Evaluation of qualitative and quantitative toxicities

  Start of study treatment until last postoperative visit. Expected average 16 weeks.

• [6R] 5,10-methylenetetrahydrofolate tissue concentration determination

  Surgery following 3 cycles (21-day cycles) of chemotherapy

• Correlation between 5,10-methylenetetrahydrofolate and HCy levels in blood

  Samples taken prior before study treatment, during 3 cycles of chemotherapy and after completion of study treatment. Expected average 20 weeks.

Study Arms (1)

Modufolin and Pemetrexed

EXPERIMENTAL

Modufolin ( \[6R\] 5,10-methylenetetrahydrofolate) and Pemetrexed

Drug: [6R] 5,10-methylenetetrahydrofolate (arfolitixorin); Drug: Pemetrexed

Interventions

[6R] 5,10-methylenetetrahydrofolate (arfolitixorin) DRUG

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.

Also known as: Modufolin, 6R-MTHF, ISO-901, arfolitixorin

Modufolin and Pemetrexed

Pemetrexed DRUG

500 mg/m2 IV on day 1 of each 21-day cycle. 3 cycles.

Also known as: ly 231514, multitargeted antifolate

Modufolin and Pemetrexed

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Isofol Medical AB: lead

Study Sites (1)

Sahlgrenska University Hospital

Gothenburg, 416 85, Sweden

Location

MeSH Terms

Conditions

Rectal Neoplasms; Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Rectal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases

Interventions

5,10-methylenetetrahydrofolic acid; Pemetrexed

Condition Hierarchy (Ancestors)

Colonic Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Bengt G Gustavsson, PhD, MD

  Sahlgrenska University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2011
• First Posted: July 19, 2011
• Study Start: April 14, 2011
• Primary Completion: October 16, 2014
• Study Completion: October 16, 2014
• Last Updated: September 9, 2020

Record last verified: 2020-09

Locations

SE (1)