Extended-duration Oxaliplatin Infusion for Gastrointestinal Cancer

Recruiting at 2 trial locations

Overseen By Olumide B. Gbolahan, MBBS, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must be taking: FOLFOX6

Disqualifiers: Peripheral neuropathy, Cardiac disease, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

Duration: Up to 60 days

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a longer infusion time of the chemotherapy drug oxaliplatin can reduce nerve damage in individuals with gastrointestinal cancers. Typically administered over two hours, the study will test whether a six-hour infusion helps patients adhere to their treatment plans without delays caused by nerve issues. Participants are divided into two groups: one receives the standard two-hour infusion, while the other receives the extended six-hour infusion. This trial suits those with gastrointestinal cancer who plan to start at least four cycles of a specific chemotherapy regimen and are not currently experiencing significant nerve damage. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot participate if you are currently receiving anticancer therapies or have received any within 14 days of starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Past studies have shown that oxaliplatin can cause side effects, including potentially serious nerve damage. However, research suggests that administering oxaliplatin over a longer period, such as 6 hours, might reduce this nerve damage. This adjustment could enable patients to continue their treatment without delays.

When patients receive oxaliplatin, some experience reactions like nausea, diarrhea, or fatigue. More severe effects, such as bleeding, have been reported but are less common. Importantly, studies have found that altering the infusion time does not increase the risk of allergic reactions or compromise safety.

Overall, while patients generally tolerate oxaliplatin well, they should be aware of possible side effects. Research continues to explore ways to make it safer and more effective. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the extended-duration oxaliplatin infusion for gastrointestinal cancer because it explores how different infusion times might improve patient outcomes. Unlike the standard 2-hour infusion, the experimental 6-hour infusion might reduce side effects and enhance the drug's effectiveness by allowing a more gradual introduction into the body, potentially improving tolerance and effectiveness. This approach could offer patients a more manageable treatment experience with the same powerful cancer-fighting benefits.

What evidence suggests that this extended-duration oxaliplatin infusion might be an effective treatment for nerve damage in gastrointestinal cancer?

Research shows that oxaliplatin, a chemotherapy drug, effectively treats advanced colorectal cancer. It is commonly used because it prevents cancer cells from growing and spreading. However, nerve damage, a frequent side effect, can be serious. In this trial, researchers will assign participants to different treatment arms to evaluate the effects of infusion duration. Some participants will receive oxaliplatin over a 2-hour period, while others will receive it over a 6-hour period. Some studies suggest that administering oxaliplatin over a longer time, like 6 hours, might reduce nerve damage. This approach could help patients continue receiving their full doses of chemotherapy without delays. Although specific data from these studies isn't detailed here, this method aims to better balance treatment and manage side effects. ^{1 3 6 7 8}

Who Is on the Research Team?

Olumide B. Gbolahan, MBBS, MSc

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for adults with gastrointestinal cancers planning to undergo at least 4 cycles of FOLFOX6 chemotherapy. They must have a confirmed diagnosis, measurable disease, and be in good enough health to participate (ECOG status 0-2). Participants need normal blood counts and organ function, and women who can become pregnant must use effective birth control.

Inclusion Criteria

Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

My white blood cell count is healthy without medication.

My cancer is confirmed and measurable or can be evaluated.

Exclusion Criteria

I do not have any severe infections or serious liver conditions.

I do not have severe heart problems like recent heart attacks or uncontrolled heart failure.

I haven't had cancer treatment in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oxaliplatin and leucovorin infusions, with courses repeating every 14 days

Up to 60 days

Every 14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Visits at 1, 3, 6, 12, and 18 months

What Are the Treatments Tested in This Trial?

Interventions

• Oxaliplatin

Trial Overview The study is testing if giving the drug Oxaliplatin over a longer period (6 hours) reduces nerve damage compared to standard infusion times. This could help patients maintain their regular chemotherapy doses without delays due to side effects.

How Is the Trial Designed?

Group I: 6-hour infusion group Experimental Treatment 3 Interventions

Patients receive oxaliplatin IV over 6 hours on day 1. Patients also receive leucovorin and fluorouracil as in the 2-hour infusion group. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Group II: 2-hour infusion group Active Control 3 Interventions

Patients receive oxaliplatin IV and leucovorin IV over 2 hours on day 1. Patients also receive a lower dose of fluorouracil IV over 2-4 minutes followed by a higher dose IV continuous over 4-6 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Oxaliplatin is already approved in European Union, United States, Canada, Japan, Switzerland, China for the following indications:

Approved in European Union as Eloxatin for:

• Colorectal cancer

Approved in United States as Eloxatin for:

• Colorectal cancer

Approved in Canada as Eloxatin for:

• Colorectal cancer

Approved in Japan as Eloxatin for:

• Colorectal cancer

Approved in Switzerland as Eloxatin for:

• Colorectal cancer

Approved in China as Ai Heng for:

• Colorectal cancer

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

Hematology/Oncology Pharmacy Association

Collaborator

Trials

1

Recruited

60+

Published Research Related to This Trial

Oxaliplatin, when combined with fluorouracil (5-FU), has shown significantly higher response rates (60% or more) in patients with untreated advanced colorectal cancer compared to lower rates when used alone (12% to 24%).

While adding oxaliplatin to 5-FU and leucovorin improves response rates and delays tumor progression, it does not appear to extend overall survival, indicating a need for further research to understand this outcome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of oxaliplatin in the treatment of colorectal cancer. Rothenberg, ML.[2022]

Oxaliplatin, used in treating metastatic colorectal cancer, has been well tolerated in over 1,700 patients during clinical trials, with manageable gastrointestinal toxicity and no significant renal toxicity.

The main concern with oxaliplatin is neurological side effects, which can be acute or longer-lasting, affecting 10 to 20% of patients after multiple cycles, but these symptoms often improve after treatment is stopped, allowing for potential resumption of therapy with proper management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oxaliplatin tolerance in the treatment of metastatic colorectal cancers]. Bugat, R.[2018]

In a study involving 206 patients with advanced colorectal carcinoma who had previously failed 5-FU-based therapy, the addition of oxaliplatin to 5-FU +/- folinic acid resulted in a 25.5% objective response rate, demonstrating its efficacy as a salvage therapy.

The median overall survival for patients receiving oxaliplatin combined with 5-FU +/- FA was 9.6 months, indicating that this treatment can provide significant benefits for patients resistant to prior fluoropyrimidine therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin added to 5-fluorouracil-based therapy (5-FU +/- FA) in the treatment of 5-FU-pretreated patients with advanced colorectal carcinoma (ACRC): results from the European compassionate-use program. Brienza, S., Bensmaïne, MA., Soulié, P., et al.[2020]

In a study of 200 patients with colon and rectal cancer receiving oxaliplatin, no significant differences in major adverse reactions (like gastrointestinal, hematotoxicity, and neurotoxicity) were found between the two groups, indicating similar safety profiles.

However, patients with rectal cancer experienced a higher incidence of allergic reactions compared to those with colon cancer, suggesting that allergic responses may be more pronounced in rectal cancer patients and warrant closer monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The incidence rate of allergic reactions induced by oxaliplatin is higher in patients with rectal cancer compared with colon cancer. Liu, T., Jin, Y., Yang, X., et al.[2023]

Oxaliplatin is a potent antineoplastic drug that works by blocking DNA replication and transcription, leading to cell death, and has shown greater efficacy than other platinum-based drugs like cisplatin in preclinical studies.

It is approved for treating metastatic colorectal cancer in several regions and shows promise in combination therapies with other agents, enhancing its effectiveness against various solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel combinations with oxaliplatin. Mani, S., Manalo, J., Bregman, D.[2022]

Oxaliplatin is a promising treatment for colorectal cancer (CRC) that works well in combination with 5-fluorouracil (5-FU), even in cases where tumors are resistant to 5-FU, as shown in controlled phase III trials.

With its excellent safety profile and unique mechanism of action, oxaliplatin can be effectively combined with other chemotherapy agents, and ongoing studies aim to optimize its use in CRC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin: a new therapeutic option in colorectal cancer. Cvitkovic, E., Bekradda, M.[2022]

In a study of 3687 cancer patients receiving oxaliplatin (OXA) chemotherapy, 42.7% experienced adverse drug reactions (ADRs), with gastrointestinal disorders being the most common (25.7%).

While most ADRs were mild to moderate, serious reactions like hypersensitivity and blood disorders were noted, emphasizing the need for careful monitoring during OXA treatment, especially since 88% of patients with ADRs showed recovery or improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of Oxaliplatin in 3,687 Patients With Cancer in China: A Post-Marketing Surveillance Study. Yu, Z., Huang, R., Zhao, L., et al.[2022]

Oxaliplatin is an effective treatment for advanced colorectal cancer, showing activity as both a first- and second-line therapy, and is well tolerated when combined with fluorouracil/leucovorin.

Unlike other platinum-based drugs, oxaliplatin has a lower risk of kidney and ear damage, but it can cause acute and chronic neurosensory symptoms, which are manageable and reversible upon stopping the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of oxaliplatin in the treatment of colorectal cancer. Haller, DG.[2018]

Nano oxaliplatin, created using a specialized method, showed a significantly faster dissolution rate in solution compared to traditional crude oxaliplatin, which could enhance patient compliance and treatment effectiveness.

In vitro studies indicated that nano oxaliplatin was about 45% more effective at inhibiting cancer cell growth than crude oxaliplatin, suggesting improved therapeutic efficacy for colorectal cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of nano oxaliplatin prepared by novel Fat Employing Supercritical Nano System, the FESNS®. Lee, SJ., Kim, YH., Lee, SH., et al.[2018]

Oxaliplatin combined with 5-FU/FA significantly improves response rates and progression-free survival in patients with advanced metastatic colorectal cancer, showing a response rate of 45% compared to 31% for irinotecan/5-FU/FA in a study of 795 patients.

While oxaliplatin can cause dose-limiting neurotoxicity, its overall tolerability is manageable, making it a valuable first- or second-line treatment option for colorectal cancer, especially in patients who have failed irinotecan-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin: a review of its use in combination therapy for advanced metastatic colorectal cancer. Simpson, D., Dunn, C., Curran, M., et al.[2022]

Oxaliplatin, a third-generation platinum-based chemotherapy drug, has been extensively studied in international clinical trials for its effectiveness across four different cancer indications.

Over the past decade, significant research in Japan has contributed to the understanding and evidence base for oxaliplatin, highlighting its ongoing potential in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oxaliplatin -- A 10-Year Trajectory]. Kanaji, S., Oki, E., Saeki, H., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03800693

2 Versus 6 Hour Oxaliplatin Infusions in Patients With ... This phase II trial studies how well giving oxaliplatin over 6 hours works in treating nerve damage in patients with gastrointestinal cancers.

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03800693/2-versus-6-hour-oxaliplatin-infusions-in-patients-with-gastrointestinal-cancers

2 Versus 6 Hour Oxaliplatin Infusions in Patients with ... This phase II trial studies how well giving oxaliplatin over 6 hours works in treating nerve damage in patients with gastrointestinal cancers.

3. withpower.com withpower.com/trial/phase-3-gastrointestinal-neoplasms-2-2019-cf8a7

Extended-duration Oxaliplatin Infusion for Gastrointestinal ... This phase II trial studies how well giving oxaliplatin over 6 hours works in treating nerve damage in patients with gastrointestinal cancers.

4. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK557690/

Oxaliplatin - StatPearls - NCBI Bookshelf - NIH Oxaliplatin is a medication used to manage and treat metastatic colorectal cancer. It is a member of the platinum-based chemotherapeutic class of drugs.

5. products.sanofi.us products.sanofi.us/eloxatin/eloxatin.html

ELOXATIN® (oxaliplatin) injection, for intravenous use Neuropathy occurred in 82% (all grades) of patients previously untreated for advanced colorectal cancer, including 19% grade 3–4; and in 74% (all grades) of ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/021492s016lbl.pdf

ELOXATIN (oxaliplatin) Label - accessdata.fda.gov These reactions included gastrointestinal bleeding, hematuria, and epistaxis. In the adjuvant treatment trial, 2 patients died from intracerebral hemorrhage [ ...

7. jhoponline.com jhoponline.com/issue-archive/2023-issues/march-2023-vol-13-special-feature/safety-outcomes-of-oxaliplatin-rapid-rate-infusion-versus-standard-rate-infusion

Safety Outcomes: Oxaliplatin Rapid vs. Standard Infusion The rapid infusion of oxaliplatin saved 30 minutes of administration time and was not associated with treatment modifications or a difference in HSR, there was ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5702800/

Oxaliplatin Can Be Safely Infused at a Rate of 1 mg/m2/min Infusing oxaliplatin at a rate of 1 mg/m 2 /min does not increase the rate of HSRs and does not compromise patient safety. This infusion rate is safe for use ...