Novel Treatments for Stomach Cancer

Recruiting at 35 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: Steroids, Immunosuppressives

Disqualifiers: HER2-positive, CNS metastases, Autoimmune disorders, 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: Average of 2 years

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new drug combinations to treat stomach cancer that cannot be surgically removed or has spread to other parts of the body. Researchers aim to determine the effectiveness and safety of these treatments, examining various drug mixes such as AZD2936 (a new potential drug) with FOLFOX or XELOX, among others. Suitable participants are those who have not yet received treatment for their advanced stomach cancer and have measurable signs of the disease. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that the treatments in this trial have varying safety levels. Here's a simple breakdown:

Studies have shown that FOLFOX is generally well-tolerated. It is often used for advanced stomach cancer and has been effective for many patients, including those with complex conditions like DIC, a blood clotting disorder. While side effects can occur, it is considered safe for most people.

XELOX, which combines capecitabine and oxaliplatin, is also regarded as safe. Research indicates it works well for advanced stomach cancer. It is a common treatment, and although some patients may experience side effects, it is generally well-accepted.

MEDI5752 is a newer treatment known as a bispecific checkpoint inhibitor, which helps the immune system attack cancer cells. Early research suggests it is safe for patients with advanced cancers, but, like other immune therapies, monitoring for immune-related side effects is important.

The investigational drugs AZD2936, AZD0901, AZD7789, rilvegostomig, and volrustomig are not as well-documented. The current phase of the study indicates they have shown enough safety in earlier stages to continue testing. However, since these are newer treatments, ongoing monitoring for side effects is crucial.

Overall, these treatments have been studied and are generally considered safe, but each patient might react differently. Open communication with the medical team about any concerns is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for stomach cancer because they employ innovative combinations and mechanisms not typically seen in current options like chemotherapy regimens FOLFOX and XELOX. AZD0901, for example, is combined with other novel agents such as volrustomig and rilvegostomig, which may offer enhanced efficacy by targeting specific pathways in cancer cells. Additionally, these treatments integrate new active ingredients like AZD7789, which could potentially improve outcomes by attacking the cancer in unique ways. This multi-faceted approach aims to provide more effective and targeted therapies compared to the traditional standards of care.

What evidence suggests that this trial's treatments could be effective for stomach cancer?

This trial will evaluate various novel treatments for stomach cancer, with participants in different arms receiving distinct treatment combinations.

One arm will study rilvegostomig combined with either XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF). Studies have shown that this combination holds promise for treating stomach cancer by targeting specific proteins (PD-1 and TIGIT) that help the immune system attack cancer cells.

Another arm will investigate AZD0901 combined with volrustomig and either 5-fluorouracil or capecitabine. Early studies suggest this combination may improve treatment by focusing on stopping cancer cell growth. Similarly, AZD0901 with AZD7789 and either 5-fluorouracil or capecitabine is being studied for its potential in treating advanced stomach cancer.

Additionally, AZD0901 combined with rilvegostomig and either 5-fluorouracil or capecitabine is under investigation for its innovative method of boosting the body's immune response to fight cancer. Lastly, another arm will study AZD7789 with XELOX or FOLFOX, which has shown a significant response rate in stomach cancer patients, suggesting it could be a potential treatment option. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Adults over 18 with a body weight above 35 kg, diagnosed with advanced gastric or gastroesophageal junction adenocarcinoma that can't be surgically removed or has spread, and who haven't been treated for it yet. Participants should have a life expectancy of at least 12 weeks and good performance status (able to carry out daily activities). Those with active infections, previous immune-oncology treatments, certain HER2-positive cancers, uncontrolled brain metastases, serious illnesses, another cancer history or uncontrollable ascites are excluded.

Inclusion Criteria

Has measurable target disease assessed by the Investigator based on RECIST 1.1

Life expectancy of at least 12 weeks

My organs and bone marrow are working well.

Exclusion Criteria

My stomach cancer is HER2 positive or uncertain but not negative.

I have been treated with immunotherapy before.

I do not have any uncontrolled illnesses.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive novel combination therapies, including Rilvegostomig, AZD0901, volrustomig, XELOX, FOLFOX, and AZD7789, depending on the substudy

Average of 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and overall survival

Average of 2 years

What Are the Treatments Tested in This Trial?

Interventions

• AZD2936
• FOLFOX
• MEDI5752
• XELOX

Trial Overview The trial is testing new combinations of drugs including chemotherapy agents like 5-Fluorouracil and Capecitabine as well as novel therapies AZD0901, Rilvegostomig, FOLFOX regimen components and Volrustomig. It aims to evaluate how effective these combinations are in treating the cancer while also monitoring safety profiles and how the body processes the drugs.

How Is the Trial Designed?

Group I: Substudy 6 Experimental Treatment 4 Interventions

AZD0901 plus AZD7789 and 5-fluorouracil or capecitabine

Group II: Substudy 5 Experimental Treatment 3 Interventions

AZD7789 plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF)

Group III: Substudy 4 Experimental Treatment 4 Interventions

AZD0901 plus rilvegostomig and 5-fluorouracil or capecitabine

Group IV: Substudy 3 Experimental Treatment 4 Interventions

AZD0901 plus volrustomig and 5-fluorouracil or capecitabine

Group V: Substudy 2 Experimental Treatment 3 Interventions

Rilvegostomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF)

Group VI: Substudy 1 Experimental Treatment 3 Interventions

Volrustomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF)

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In a phase II trial involving 63 patients with advanced gastric cancer, the combination of oxaliplatin, irinotecan, and fluorouracil/folinic acid showed a response rate of 33%, indicating it is an effective treatment option for this condition.

The treatment was generally well-tolerated, with manageable side effects; however, significant toxicities included neutropenia in 59% of patients and neurotoxicity in 33%, highlighting the need for monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin, irinotecan, and fluorouracil/folinic acid in advanced gastric cancer: a multicenter phase II trial of the Southern Italy Cooperative Oncology Group. Comella, P., Lorusso, V., Maiorino, L., et al.[2018]

The maximum tolerated doses (MTDs) for sunitinib combined with chemotherapy in advanced gastric cancer were established, with sunitinib showing a dose of 25 mg/day for the XP regimen and 37.5 mg/day for the XELOX regimen, indicating a structured approach to optimizing treatment.

Both treatment combinations (sunitinib/XP and sunitinib/XELOX) demonstrated significant antitumor activity, with median progression-free survival of 6.4 months and an objective response rate of approximately 46%, suggesting efficacy despite a high incidence of hematologic adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of sunitinib plus capecitabine/cisplatin or capecitabine/oxaliplatin in advanced gastric cancer. Lee, KW., Park, SR., Oh, DY., et al.[2022]

The study compared the efficacy and safety of two chemotherapy regimens, XELOX and FOLFOXs, in 1585 patients with advanced gastric cancer, but found no significant difference in overall response rate or clinical benefit rate between the two treatments.

XELOX was associated with lower risks of nausea, stomatitis, diarrhea, and alopecia compared to FOLFOXs, but had a higher risk of hand-foot syndrome, suggesting it may be a safer option despite similar efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine plus oxaliplatin (XELOX) compared with 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOXs) in advanced gastric cancer: meta-analysis of randomized controlled trials. Xu, HB., Huang, F., Su, R., et al.[2022]

Recent advancements in the treatment of metastatic gastric cancer include the use of immune-checkpoint inhibitors like nivolumab and pembrolizumab, which have shown significant improvements in overall survival, particularly in Asian patients and those with PD-L1 positivity.

Combination therapies involving PD-1/PD-L1 antibodies with CTLA4 or VEGF-R2 inhibitors, as well as chemotherapy, are being explored and show promising results, potentially expanding the number of patients who can benefit from these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibition in Gastro-Oesophageal Cancer. Smyth, E., Thuss-Patience, PC.[2019]

The phase I trial of MEDI5752, a bispecific antibody that targets both PD-1 and CTLA4, shows that the drug is well tolerated by patients.

Preliminary results indicate that MEDI5752 is active in treating various tumor types, with durable responses observed, suggesting potential effectiveness in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

Nivolumab, an immune checkpoint inhibitor, was successfully used as a third-line treatment for a 69-year-old woman with unresectable advanced gastric cancer, leading to a complete response after nine courses despite initial disease progression.

The patient experienced interstitial pneumonia as an adverse effect, but the therapeutic benefits of nivolumab appeared to persist for at least 9 months after treatment cessation, suggesting a potential long-lasting impact on cancer control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical complete response after nivolumab administered as a third-line treatment for unresectable advanced gastric cancer with peritoneal dissemination: A case report. Komo, T., Suzuki, T., Tazawa, H., et al.[2021]

In a study of 51 patients with advanced or recurrent gastric cancer, the FOLFOX-6 chemotherapy regimen resulted in a 41.2% overall response rate, with 3 complete responses and 18 partial responses, indicating good efficacy.

The treatment had an acceptable safety profile, with significant toxicities including grade 3/4 neutropenia in 9.8% and anemia in 7.8% of patients, but no treatment-related deaths were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of oxaliplatin, fluorouracil and folinic acid (FOLFOX-6) as first-line chemotherapy in advanced or recurrent gastric cancer. Luo, HY., Xu, RH., Zhang, L., et al.[2022]

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 44 previously untreated patients with advanced gastric cancer, the combination of cetuximab and XELOX chemotherapy resulted in a significant overall response rate of 52.3%, with median progression-free survival of 6.5 months and overall survival of 11.8 months.

The treatment was generally safe, with most side effects being mild to moderate (grade 1 or 2), such as anemia and asthenia, and serious hematologic toxicities were rare, indicating that cetuximab combined with XELOX is a viable first-line option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective phase II study of cetuximab in combination with XELOX (capecitabine and oxaliplatin) in patients with metastatic and/or recurrent advanced gastric cancer. Kim, C., Lee, JL., Ryu, MH., et al.[2021]

In a study of 65 patients with KRAS wild-type metastatic colorectal cancer who were resistant to standard chemotherapy, the combination of panitumumab and irinotecan resulted in an objective response rate of 29.2%, with a median overall survival of 9.7 months.

The treatment was particularly effective in patients without additional mutations, showing a 46.3% response rate, while those with other mutations (NRAS, BRAF, or rare KRAS) did not respond, highlighting the importance of biomarker selection in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab combined with irinotecan for patients with KRAS wild-type metastatic colorectal cancer refractory to standard chemotherapy: a GERCOR efficacy, tolerance, and translational molecular study. André, T., Blons, H., Mabro, M., et al.[2023]

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