Novel Treatments for Stomach Cancer

Recruiting at 28 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 is testing new combinations of drugs to treat advanced stomach cancer that can't be removed by surgery or has spread. Researchers want to see if these drug combinations are effective and safe, and how the body handles them. A group of patients will participate to find the best dose.

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 the XELOX treatment generally safe for humans?

The XELOX treatment, which combines capecitabine and oxaliplatin, has been studied for safety in patients with advanced gastric cancer. These studies suggest that XELOX is generally safe, but like all treatments, it can have side effects, which should be discussed with a healthcare provider. ^{1 2 3 4 5}

What makes the drug AZD2936, FOLFOX, MEDI5752, XELOX unique for stomach cancer treatment?

This treatment is unique because it combines traditional chemotherapy (FOLFOX and XELOX) with MEDI5752, a novel bispecific antibody that targets two immune checkpoints, PD-1 and CTLA4, potentially enhancing the immune system's ability to fight cancer. This combination aims to improve outcomes by leveraging both chemotherapy and advanced immunotherapy. ^{4 5 6 7 8}

What data supports the effectiveness of the drug AZD2936, FOLFOX, FOLFOX4, FOLFOX6, FOLFOX7, MEDI5752, Volrustomig, MEDI-5752, PD-1/CTLA-4 bispecific mAb, PD-l/CTLA-4 DuetMab, XELOX, Capecitabine/Oxaliplatin for stomach cancer?

Research shows that combinations like FOLFOX and XELOX, which include drugs like oxaliplatin and capecitabine, are effective in treating advanced gastric (stomach) cancer. Additionally, MEDI5752, which targets immune checkpoints, has shown promising results in various tumors, suggesting potential benefits for stomach cancer as well. ^{4 5 7 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]

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. Germany 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. [2018]

2. Switzerland 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. [2022]

3. Germany 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. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

5. China pubmed.ncbi.nlm.nih.gov

[Preliminary study of XELOX regimen as the first-line chemotherapy in advanced or recurrent gastric cancer]. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Phase I study of sunitinib plus capecitabine/cisplatin or capecitabine/oxaliplatin in advanced gastric cancer. [2022]

7. United States 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. [2021]

8. England 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. [2023]

9. Netherlands 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. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibition in Gastro-Oesophageal Cancer. [2019]