Neoplasms

Digestive System Diseases

All Conditions

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Bone Density Conservation Agents

Vitamins

Leucovorin

Fluorouracil

Levoleucovorin

Calcium

Calcium, Dietary

Folinic Acid

Infusion of Na-Lev plus 5-FU (unique administration by one 48h-infusional pump)

Infusion of Ca-Lev followed by infusion of 5-FU (two separated administrations by using one plastic bag followed by one 48h-infusional pump)

Alessandro Passardi, MD

Prospective observational study comparing calcium and sodium levofolinate in combination with 5FU/or in FOLFIRI regimen on patients affected by gastrointestinal cancer (any site of disease along with gastrointestinal tract) who have been prescribed FOLFIRI in standard clinical practice.

This is an observational, perspective trial on patients affected by gastrointestinal cancer (any site of disease along with gastrointestinal tract) who have been prescribed FOLFIRI in standard clinical practice. All patients will be treated and monitored according to the local clinical practice. No additional procedures/patient visits in comparison with the usual clinical practice are planned for the study.

Prospective Observational Study Comparing Calcium and Sodium Levofolinate in Combination With 5-Fluorouracil (5FU) /or in FOLFIRI Regimen

Prospective Observational Study Comparing Calcium and Sodium Levofolinate in Combination With 5FU/or in FOLFIRI Regimen

Safety profiles of Na-Lev and Ca-Lev when administered in combination with 5-FU in FOLFIRI regimen to cancer patients under standard clinical practice. Reported Adverse Events (AE) will be summarized by system organ class, seriousness, severity (according to NCI -Common Terminology Criteria for Adverse Events, CTCAE version 4.0) and relationship to study drug. Comparison between groups will be performed using non parametric statistical test.

organizational impact that the introduction of Na-Lev would have on Drug production and delivery. The set-up times of preparation of Na-lev (by manual procedure) with respect to Ca-lev will be measured: for each individual therapy prescribed by clinicians the timing of the manual preparation in Official Pharmaceutical Lab (LFO) will be measured by chronometer, for the entire duration of each production line.

economical impact hat the introduction of Na-Lev would have on Drug production and delivery. The set-up times of preparation of Na-lev (by manual procedure) with respect to Ca-lev will be measured: after preparation, the difference in waste of residual drug will be measured (if present) for each production. Quantity of residual drugs will be reported for each product line taking account of weight of enrolled patients.

Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Symptoms and General Pathology

Neoplasm Metastasis

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Hematinics

Oxaliplatin

Bevacizumab

Liver Extracts

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folate

Vitamin B9

Participants will receive combination therapy of bevacizumab 5 mg/kg IV dose and mFOLFOX-6 (Levofolinic acid, 5-FU and oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy).

Participants will receive 5-FU 400 mg per meter-squared (mg/m\^2) IV dose on Day 1 of each 2 weeks' cycle followed by 2400 mg/m\^2, continuous infusion over 46 hours up to 12 cycles.

5-Fluorouracil (5-FU)

Participants will receive 5 mg/kg bevacizumab IV dose on Day 1 of each 2 weeks' cycle up to Cycle 5 and thereafter cycles 7 to 12; followed by maintenance therapy of 5 mg/kg IV every 2 weeks up to 52 weeks (26 cycles).

Participants will receive levofolinic acid 200 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle up to 12 cycles.

Levofolinic acid

Participants will receive oxaliplatin 85 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle up to 12 cycles.

Clinical Trials

The multicenter, open-label, single-arm, non-randomized, two-stage Simon's design, phase II study (The CLMO-001 Trial) will evaluate the efficacy and safety of bevacizumab in combination with mFOLFOX-6 (Levofolinic acid, 5-Fluorouracil \[5-FU\] and oxaliplatin) in participants with colorectal cancer and liver metastases. Participants will receive combination therapy of bevacizumab 5 milligrams per kilogram (mg/kg) intravenous (IV) dose and mFOLFOX-6 every 2 weeks during Cycles 1-5 and Cycles 7-12. Participants will receive mFOLFOX-6 alone (without bevacizumab) on Cycle 6. In between Cycle 6 and 7, participants will undergo liver surgery if operable. Thereafter participants will receive bevacizumab (5 mg/kg IV every 2 weeks) alone for 52 weeks (26 cycles) after the end of the post-operative phase (maintenance therapy). At the end of the preoperative treatment phase (Cycles 1-6), participants showing different alternative conditions admitted by the protocol will undergo different management (alternative study designs 1 to 3).

A Study of Bevacizumab and Modified FOLFOX-6 (mFOLFOX-6) in Participants With Metastatic Colorectal Cancer

A Multi-center, Open-label Clinical Trial to Evaluate the Objective Response Rate of Bevacizumab in Combination With Modified FOLFOX-6 Followed by One Year of Maintenance With Bevacizumab Alone in Patients With Initially Not or Borderline Resectable Colorectal Liver Metastases (The CLMO-001 Trial)

ORR was defined as the percentage of participants with shrinkage (partial response \[PR\]) or disappearance of cancer (complete response \[CR\]). Tumor response was evaluated according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). The same method of tumor measurement and assessment had to be used to characterize each lesion throughout the study. Tumor assessment consisted of computerized tomography (CT) scan (abdomen + pelvis + chest) or contrast-enhanced magnetic resonance imaging (CE-MRI) (abdomen + pelvis) + non CE-CT (chest) according to the choice of the center. CR, Disappearance of all target lesions; PR, \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

ORR was defined as the percentage of participants with shrinkage (PR) or disappearance of cancer (CR). Tumor response was evaluated according to the RECIST v1.1. The same method of tumor measurement and assessment had to be used to characterize each lesion throughout the study. Tumor assessment consisted of CT scan (abdomen + pelvis + chest) or CE-MRI (abdomen + pelvis) + non CE-CT (chest) according to the choice of the center. CR, Disappearance of all target lesions; PR, \>=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR.

The percentage of participants achieving R0/R1 liver resection was defined as the percentage of participants achieving R0 surgery (no residual tumor) plus percentage of participants achieving R1 surgery (surgical margin with microscopic residual tumor).

DFI was defined as the time from the date of R0/R1 surgery to the date of disease relapse or death due to any cause. Participants who did not progress were considered censored at the date of the last assessment performed. For participants receiving two-stage resection, the date of R0/R1 surgery was the date of the second surgery. Participants, who did not receive surgery and participants without R0/R1 surgery were censored at Day 1. DFI was calculated as follows: DFI (months) = (\[Date of R0/R1 surgery - Date of 1st relapse/Death\] + 1)/30

PFS was defined as the time from the date of first study drug administration to the date of disease progression or death due to any cause, whichever came first. Progression was defined according to RECIST, v1.1 as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions. Participants, who did not progress were censored at the date of the last assessment performed. Participants who withdrew from the study without documented progression and for whom an electronic case report form (eCRF) existed as evidence that evaluations had been made, were censored at the date of the last tumor assessment when the participant was known to be progression-free. Participants without post-baseline tumor assessments, but known to be alive were censored at the time of first study drug administration. PFS was calculated: PFS (months) = (\[Date of Event - Date of first study drug administration\] + 1)/30.

OS was defined as the time from the date of first study drug administration to the date of death due to any cause. Participants who were alive at the time of the analysis were censored at the last date the participant was known to be alive. OS was calculated as follows: OS (months) = (\[Date of Death - first study drug administration\] + 1)/30

Hoffmann-La Roche

The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.

Combination therapy of bevacizumab and mFOLFOX-6 (Levofolinic acid, 5-Fluorouracil \[5-FU\], oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy). 5-FU: 400 mg/meter-squared (mg/m\^2) IV dose on Day 1 of each 2 weeks' cycle followed by 2400 mg/m\^2, continuous infusion over 46 hours; Bevacizumab: 5 mg/kg IV on Day 1 of each 2 weeks' cycle; Levofolinic acid: 200 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle; Oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle

Bevacizumab + mFOLFOX-6

Age, Continuous

Sex: Female, Male

The intent-to-treat analysis set (ITT), which included all enrolled participants, who received at least one dose of any study medication.

Medical Communications

The ITT set, which included all enrolled participants, who received at least one dose of any study medication.

Objective Response Rate (ORR) in the Intent-to-treat (ITT) Analysis Set

The PPAS included all subjects in the ITT set, who did not experience any major protocol violations.

Objective Response Rate (ORR) in the Per-protocol Analysis Set (PPAS)

Percentage of Participants Achieving No Residual Tumor (R0)/Surgical Margin With Microscopic Residual Tumor (R1) Liver Resection

Disease-free Interval (DFI)

Progression-Free Survival (PFS)

Overall Survival (OS)

Bevacizumab + Modified FOLFOX-6 (mFOLFOX-6)

Overall Study

Rectal Neoplasms

Raltitrexed

Folic Acid Antagonists

Enzyme Inhibitors

Preoperative radiation therapy and combination chemotherapy plus bevacizumab

Radiation therapy will be administered at the total dose of 45 Gy, given with five weekly fractions over a period of 5 weeks. The daily fraction dose will be 1.8 Gy

Radiation therapy

100 mg/m2 on day 1 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy)

2.5 mg/m2 on day 1 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1) , an additional 2 cycles of chemotherapy will be given after radiation therapy)

250 mg/m2 on day 2 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy)

levofolinic acid

800 mg/m2 on day 2 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy)

5-fluorouracil

will be given by intravenous infusion at the dose of 5 mg/kg concurrent with chemotherapy and radiotherapy every 2 weeks for 4 cycles from -14 days to start chemo-radiotherapy (classical schedule) or 4 days before the concurrent administration of chemotherapy and radiation therapy for 2 cycles if the number of TRG1 was not reached in the first stage (statistical design) with the classical schedule (for patients with resectable organ metastases (M1), one additional administration of bevacizumab will be given after radiation therapy)

Antonio Avallone, M.D.

The purpose of this study is to evaluate the use of chemotherapy, radiation therapy and bevacizumab before surgery in patients with locally advanced rectal cancer (LARC).

To determine the pathological complete response (pCR-TRG1) rate in patients treated with 2 different schedule of bevacizumab plus primary chemotherapy and radiotherapy of the pelvic region when optimal surgery is applied.

Bevacizumab will be given by intravenous infusion at the dose of 5 mg/kg concurrent with chemotherapy and radiotherapy every 2 weeks for 4 cycles from -14 days to start chemo-radiotherapy (classical schedule) or 4 days before the concurrent administration of chemotherapy and radiation therapy for 2 cycles if the number of TRG1 was not reached in the first stage with the classical schedule Simon's methods will be used to calculate sample size.Setting a and b errors as 0.05 and 0.20, respectively, and defining as minimum activity of interest (p0) a TRG1 rate=30%. In order to demonstrate a TRG1 rate ≥50% (p1), at least 6 TRG1 on the first 15 patients, and at least 19 TRG1 on a total of 46 patients should be reported in the first and second stage, respectively.

Bevacizumab With Pelvic Radiotherapy And Primary Chemotherapy in Patients With Poor-Risk Rectal Cancer

Bevacizumab With Pelvic Radiotherapy And Primary Chemotherapy in Patients With Poor-Risk Rectal Cancer: the BRANCH Trial

Complete tumor regression rate (TRG1) was the ratio of patients with TRG1, graded at surgical resection, and total patients included in the study, expressed in percentage.

Tumor regression grade (TRG) was misured according to the Mandard Scale. Briefly,TRG1 was a complete tumor regression (regardless of the presence of acellular mucine lakes), and TRG2 was a nearly complete tumor regression with extensive fibrosis; TRG3 presented with clear evidence of residual cancer cells but with predominant fibrosis;TRG4 was a residual of cancer cells outgrowing fibrosis; TRG5 was the absence of regressive changes.

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Sphincter preservation in patients with tumor \< 5 cm from anal verge in 8 weeks after chemoradiation therapy

PFS was calculated from the date of the initial treatment until tumor progression or relapse, death for any cause or last follow up.

Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

OS was calculated from the date of initial treatment to the date of death for any cause or last follow up.

Clinical response was assessed before surgery with the same imaging modalities that were used for the inclusion in the study.

Clinical response rate was the ratio between complete and partial response, evaluated by RECIST CRITERIA, and total of patients evaluated, expressed in percentage of patients.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Number of patients with metastatic lymphnodes at pathology exam after surgery.

National Cancer Institute, Naples

Preoperative radiation therapy and combination chemotherapy plus bevacizumab

Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemoradiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A)

Concomitant - Schedule A

Preoperative radiation therapy and combination chemotherapy plus bevacizumab

Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B).

Sequential - Schedule B

Total

Italian

Race/Ethnicity, Customized

Italy

Region of Enrollment

Distance of mesorectal Fascia (MRF) < 5 mm

Dr. Antonio Avallone

Percentage of Patients With Complete Tumor Regression Rate (TRG1)

Number of Participants With Adverse Events

Number of Patients With Sphincter Preservation

PFS for the schedule A was not calculated because the number of TRG1 (2 out of 16 patients) was statistically inconsistent with the hypothesis of activity (30%) to be tested and, consequently, the accrual was early terminated.

Progression Free Survival (PFS)

OS for the schedule A was not calculated because the number of TRG1 (2 out of 16 patients) was statistically inconsistent with the hypothesis of activity (30%) to be tested and, consequently, the accrual was early terminated.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prospective Observational Study Comparing Calcium and Sodium Levofolinate in Combination With 5-Fluorouracil (5FU) /or in FOLFIRI Regimen	NCT04680104	Gastrointestina... CALCIUM LEVOFOL... SODIUM LEVOFOLI...		18 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Prospective Observational Study Comparing Calcium and Sodium Levofolinate in Combination With 5-Fluorouracil (5FU) /or in FOLFIRI Regimen	NCT04680104	Gastrointestina... CALCIUM LEVOFOL... SODIUM LEVOFOLI...		18 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Prospective Observational Study Comparing Calcium and Sodium Levofolinate in Combination With 5-Fluorouracil (5FU) /or in FOLFIRI Regimen	NCT04680104	Gastrointestina... CALCIUM LEVOFOL... SODIUM LEVOFOLI...		18 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
A Study of Bevacizumab and Modified FOLFOX-6 (mFOLFOX-6) in Participants With Metastatic Colorectal Cancer	NCT01383707	Colorectal Canc...	5-Fluorouracil ... Bevacizumab Levofolinic aci... Oxaliplatin	18 Years -	Hoffmann-La Roche
Prospective Observational Study Comparing Calcium and Sodium Levofolinate in Combination With 5-Fluorouracil (5FU) /or in FOLFIRI Regimen	NCT04680104	Gastrointestina... CALCIUM LEVOFOL... SODIUM LEVOFOLI...		18 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Bevacizumab With Pelvic Radiotherapy And Primary Chemotherapy in Patients With Poor-Risk Rectal Cancer	NCT01481545	Rectal Cancer	Radiation thera... Oxaliplatin Raltitrexed levofolinic aci... 5-fluorouracil Bevacizumab	18 Years -	National Cancer Institute, Naples

Spots Global Cancer Trial Database for levofolinic acid