Modified Capecitabine + Oxaliplatin for Gastrointestinal Cancers

Enrolling by invitation at 1 trial location

Overseen By Randall F Holcombe, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Vermont Medical Center

Must be taking: Capecitabine, Oxaliplatin

Must not be taking: Irinotecan

Disqualifiers: Hematologic, Liver, Renal, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of administering two cancer drugs, capecitabine (Xeloda) and oxaliplatin (Eloxatin), to determine if it reduces side effects in individuals with certain gastrointestinal (GI) cancers. The trial examines how the body tolerates this modified schedule compared to standard treatment plans. It seeks participants with GI cancer scheduled for non-curative treatment with these drugs for over three months, who may also receive other cancer medications. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it allows the use of certain other anti-cancer drugs. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the combination of capecitabine and oxaliplatin, known as XELOX, has been tested in several studies. Common side effects include nausea, vomiting, diarrhea, and nerve-related issues like tingling sensations. One study found that serious side effects occurred in about 7% of patients.

Another study indicated that while XELOX treatment is generally safe and effective, some patients stopped treatment due to side effects. Despite this, the treatment avoids problems related to central venous catheters, which are tubes placed into a large vein.

Overall, these studies suggest that XELOX has a manageable safety profile, but side effects do occur. This trial aims to determine if a different schedule can reduce these issues. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for gastrointestinal cancers?

Researchers are excited about the modified capecitabine and oxaliplatin treatment because it offers a unique dosing schedule that could potentially enhance effectiveness and reduce side effects compared to traditional chemotherapy regimens. Unlike standard treatments for gastrointestinal cancers, which often involve continuous dosing, this approach administers capecitabine in a 7-days-on, 7-days-off cycle. This intermittent schedule may allow the body more time to recover between doses, potentially improving patient outcomes and quality of life. Additionally, the combination with oxaliplatin, given every two weeks, targets cancer cells with a one-two punch, aiming to increase the overall impact on the tumor while minimizing toxicity.

What evidence suggests that this modified treatment could be effective for gastrointestinal cancers?

This trial will evaluate a modified administration schedule of capecitabine and oxaliplatin for gastrointestinal cancers. Studies have shown that combining these drugs effectively treats certain stomach and intestinal cancers. For example, the XELOX treatment plan, which uses these two drugs, demonstrated a 41.5% success rate in shrinking tumors in patients with advanced or returning stomach cancer. When taken as directed, capecitabine disrupts the DNA of cancer cells, stopping their growth. Oxaliplatin, administered through an IV, helps kill cancer cells and prevent their growth. Together, these drugs offer a strong treatment option for people facing these types of cancers. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for patients with gastrointestinal (GI) cancers who are set to receive non-curative treatment with CAPOX or FOLFOX for over 3 months. They don't need measurable disease but must have proper kidney, blood, and liver function. Patients already on certain other cancer treatments can join, but not those on additional cytotoxic chemotherapy.

Inclusion Criteria

My treatment plan includes CAPOX or FOLFOX for more than 3 months, not aimed at curing.

I have a gastrointestinal cancer.

Exclusion Criteria

My kidney function is within the required range for chemotherapy.

My blood tests show enough neutrophils and platelets for chemotherapy.

My liver tests are within the required range for chemotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oxaliplatin IV every 2 weeks and capecitabine orally for 7 days followed by 7 days off, with cycles repeating every 14 days

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Oxaliplatin

Trial Overview The study tests a modified schedule of capecitabine and oxaliplatin (mCAPOX) to see if it causes less toxicity than the standard regimens. It's a single-arm study focusing on how tolerable this new schedule is and what toxic effects it might have.

How Is the Trial Designed?

Group I: Modified administration schedule of capecitabine with oxaliplatin Experimental Treatment 2 Interventions

* Oxaliplatin (85mg/m2), will be administered IV every 2 weeks * Capecitabine (1000mg/m2) will be given twice daily, administered orally (PO) for 7 days, followed by 7 days with no capecitabine Cycles will repeat every 14 days.

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

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

University of Vermont Medical Center

Lead Sponsor

Trials

46

Recruited

25,900+

Published Research Related to This Trial

The XELOX regimen, combining oxaliplatin and capecitabine, demonstrated a 41.5% overall response rate in 41 patients with advanced or recurrent gastric cancer, indicating its efficacy in this challenging condition.

The treatment was associated with manageable toxicity, with only a few patients experiencing severe side effects, such as grade 3-4 neural toxicity and hematological issues, suggesting it is a viable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preliminary study of XELOX regimen as the first-line chemotherapy in advanced or recurrent gastric cancer]. Min, N., He, BF., Zhang, LS., et al.[2020]

In a study of 50 patients with nonmetastatic colorectal cancer, adverse reactions were more frequent with the XELOX regimen (capecitabine combined with oxaliplatin), particularly neurotoxicity, thrombocytopenia, and neutropenia, compared to capecitabine monotherapy.

The type of capecitabine formulation (innovative vs. generic) did not significantly affect the safety profile; instead, the chemotherapy scheme used was the main factor influencing the occurrence of adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine safety profile, innovative and generic adjuvant formulation of nonmetastatic colorectal cancer. Sánchez-Gundín, J., Torres-Suárez, AI., Fernández-Carballido, AM., et al.[2020]

In a phase III trial involving 1,886 patients with stage III colon cancer, the combination of capecitabine and oxaliplatin (XELOX) demonstrated a manageable safety profile, with treatment-related adverse events occurring at similar rates to the standard treatment of fluorouracil/leucovorin (FU/LV).

Patients receiving XELOX experienced less diarrhea and alopecia but had higher rates of neurosensory toxicity and hand-foot syndrome compared to those on FU/LV, indicating that while XELOX is generally well-tolerated, it may have specific side effects that need monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. Schmoll, HJ., Cartwright, T., Tabernero, J., et al.[2022]

In a study of 24 patients with advanced gastric cancer, the combination of oxaliplatin and capecitabine showed an overall response rate of 29.2%, indicating it can be an effective second-line chemotherapy option.

The treatment was generally well tolerated, with major side effects including bone marrow suppression and nausea/vomiting, and it provided a median time to tumor progression of 5 months and a median duration of remission of 8 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oxaliplatin plus capecitabine as a second line chemotherapy for patients with advanced gastric cancer]. Qian, J., Qin, SK., Mei, JF., et al.[2018]

In a study of 1002 patients with untreated advanced esophagogastric cancer, capecitabine was found to be noninferior to fluorouracil in terms of overall survival, with a hazard ratio of 0.86, indicating it is an effective alternative.

Oxaliplatin demonstrated similar efficacy to cisplatin, with a hazard ratio of 0.92, and was associated with fewer severe side effects, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine and oxaliplatin for advanced esophagogastric cancer. Cunningham, D., Starling, N., Rao, S., et al.[2023]

In a phase-III trial involving 306 patients with metastatic colorectal cancer, XELOX (capecitabine plus oxaliplatin) was found to be non-inferior to FOLFOX-6 (5-fluorouracil/leucovorin plus oxaliplatin) in terms of efficacy, indicating it is a viable first-line treatment option.

Patients receiving XELOX reported greater convenience and satisfaction, spending fewer days on hospital visits and losing less time from work or daily activities compared to those on FOLFOX-6, while maintaining similar quality of life scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality-of-life findings from a randomised phase-III study of XELOX vs FOLFOX-6 in metastatic colorectal cancer. Conroy, T., Hebbar, M., Bennouna, J., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2361232/

A phase II study of capecitabine plus 3-weekly oxaliplatin ... Capecitabine 1250 mg m−2 twice daily on days 1–14 every 3 weeks has also been shown to be active (overall response rate 28%; stable disease 36%) and well ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419618740

a phase I, dose-escalation study in patients with advanced ... This study has demonstrated that administration of capecitabine in combination with oxaliplatin is a promising new treatment option for patients with solid ...

3. withpower.com withpower.com/trial/phase-2-neoplasms-9-2024-22caf

Modified Capecitabine + Oxaliplatin for Gastrointestinal ... The XELOX regimen, combining oxaliplatin and capecitabine, demonstrated a 41.5% overall response rate in 41 patients with advanced or recurrent gastric cancer, ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1713709

Duration of Adjuvant Chemotherapy for Stage III Colon ... For fluorouracil and capecitabine, the mean percentage of doses that were delivered was 92.4% and 91.2%, respectively, in the 3-month therapy ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)61874-0/pdf

Capecitabine (Xeloda®) in combination with oxaliplatin Results: The recommended dosing schedule is oral capecitabine 1000 mg/m2 twice daily (days 1–14) with i.v. oxaliplatin 130 mg/m2 (day 1) in a 21-day ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/12056706/

Capecitabine (Xeloda) in combination with oxaliplatin The most frequent treatment-related adverse events occurring during the study were gastrointestinal (nausea/vomiting, diarrhea) and neurological (dysesthesia, ...

7. ascopubs.org ascopubs.org/doi/abs/10.1200/OP-24-00647

Real-World Tolerability of Capecitabine and Oxaliplatin in ... This study highlights that a substantial number of patients with localized CRC undergoing curative-intent treatment with CAPOX do not complete the planned ...

8. medicaljournalssweden.se medicaljournalssweden.se/actaoncologica/article/view/26591/31296

View of Capecitabine and oxaliplatin (XELOX) is safe and ... Another major advantage of XELOXregimen is the avoidance of a CVC and its relatedcomplications.In conclusion, the 3-weekly XELOX, is safe,active and well ...

9. cancernetwork.com cancernetwork.com/view/capecitabineoxaliplatin-combination-reduces-treatment-costs-metastatic-colorectal-cancer

Capecitabine/Oxaliplatin Combination Reduces Treatment ... Results of a large phase II trial usingXELOX to treat metastatic colorectal cancer demonstrated a 55% response rate andfavorable safety data, with 7.6 months ...

10. asco.org asco.org/abstracts-presentations/ABSTRACT77463

Adjuvant capecitabine and oxaliplatin for gastric cancer Serious XELOX-related grade 3/4 AEs occurred in 34/496 patients (7%). There were 62/496 (13%) and 80/476 (17%) deaths on study in the safety populations of ...