Preoperative Therapy for Stomach Cancer

(TOPGEAR Trial)

Not currently recruiting at 64 trial locations

Overseen By Christine Aiken

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Australasian Gastro-Intestinal Trials Group

Disqualifiers: Metastatic disease, Prior chemotherapy, Cardiac failure, others

Stay on Your Current Meds You can continue your current medications while participating

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new preoperative treatments for stomach cancer by adding chemoradiotherapy (a combination of chemotherapy and radiation) to standard chemotherapy before surgery. The researchers aim to determine if this approach can increase the chances of a complete response and improve overall survival rates for patients undergoing surgery to remove stomach cancer. They seek participants with stomach cancer that can potentially be surgically removed and has not spread to other parts of the body. This trial may suit individuals diagnosed with locally advanced stomach cancer who have not received prior chemotherapy or radiotherapy. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to potentially groundbreaking advancements in stomach cancer treatment.

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 to get specific guidance based on your situation.

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

Research has shown that both preoperative chemoradiotherapy and preoperative chemotherapy have been studied for their safety in humans.

Studies have found that preoperative chemoradiotherapy can cause stomach and digestive issues, such as nausea or diarrhea, in about 28% of patients. However, overall survival rates remain similar to those who receive only chemotherapy, indicating that while side effects exist, the treatment is generally manageable.

For preoperative chemotherapy, research indicates it is safe and practical. Studies suggest that minimally invasive surgery after chemotherapy is safe for patients with advanced stomach cancer. Chemotherapy alone is a standard treatment and has been tested in many trials, supporting its safety.

These findings demonstrate that while both treatments can have side effects, they are generally well-tolerated by patients with stomach cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these preoperative therapies for stomach cancer because they combine chemotherapy and chemoradiotherapy to potentially improve patient outcomes. Unlike the standard of care, which typically involves chemotherapy alone, these treatments integrate radiation to target tumors more effectively before surgery. The combinations of drugs used, such as epirubicin, cisplatin, and 5-fluorouracil, are designed to shrink tumors more efficiently and reduce the risk of cancer returning. Additionally, using capecitabine as an oral alternative to 5-fluorouracil offers a more convenient administration route, which can improve patient comfort and adherence.

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

Research has shown that combining chemotherapy and radiation before surgery might offer long-term benefits for treating advanced stomach cancer. In this trial, some participants will receive preoperative chemoradiotherapy, which studies have shown results in a median survival of 46 months. Another study noted that adding radiation helped prevent cancer growth in the treated area. Meanwhile, other participants will receive preoperative chemotherapy alone, which has demonstrated that about 50.1% of patients were alive three years later. This suggests that chemotherapy alone can significantly extend life for some patients. Both treatment options are promising, but adding radiation might help stop local cancer growth. ^{6 7 8 9 10}

Who Is on the Research Team?

Trevor Leong, MBBS, MD

Principal Investigator

Peter MacCallum Cancer Centre, Australia

Are You a Good Fit for This Trial?

This trial is for adults over 18 with certain stages of stomach cancer (Stage IB-III) that can potentially be removed by surgery. Participants must have a good performance status, meaning they're able to carry out daily activities with minimal assistance. They need normal blood counts and liver function, adequate kidney function, and if there's a history of heart disease or they are over 60, their heart pumping function needs to be confirmed as sufficient.

Inclusion Criteria

My cancer is between stage IB (only T1N1) and IIIC according to AJCC 7th edition.

My liver tests are within the required range.

Bone marrow: Haemoglobin >=90 g/L, Absolute neutrophil count (ANC) >=1.5 x 10⁹ /L, White blood cell count >=3 x 10⁹ /L, Platelet count >=100 x 10⁹ /L

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Chemotherapy

Participants receive 2-3 cycles of preoperative chemotherapy with epirubicin, cisplatin, and 5-fluorouracil or alternative regimens

6-9 weeks

Preoperative Chemoradiotherapy

Participants in the experimental arm receive 5 weeks of preoperative chemoradiotherapy

5 weeks

Surgery

Participants undergo gastric resection surgery

Postoperative Chemotherapy

Participants receive 3-4 cycles of adjuvant chemotherapy with epirubicin, cisplatin, and 5-fluorouracil or alternative regimens

9-12 weeks

Follow-up

Participants are monitored for disease progression, survival, and toxicities

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Epirubicin + cisplatin + 5-fluorouracil OR epirubicin + cisplatin + capecitabine OR epirubicin + oxaliplatin + capecitabine OR 5-Fluorouracil + leucovorin + oxaliplatin + docetaxel
• Gastric resection
• Post-operative chemotherapy
• Preoperative chemoradiotherapy
• Pre-operative chemotherapy

Trial Overview The TOPGEAR trial is testing whether adding chemoradiotherapy (a combination of chemotherapy drugs and radiation therapy) before surgery improves outcomes compared to just chemotherapy before surgery in patients with resectable gastric cancer. After the initial treatments, all patients will undergo surgery followed by more chemotherapy.

How Is the Trial Designed?

Group I: Preoperative chemoradiotherapy Experimental Treatment 3 Interventions

2 cycles preoperative chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine). OR epirubicin + oxaliplatin + capecitabine OR 3 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel 5 weeks preoperative chemoradiotherapy. Gastric resection. 3 cycles adjuvant chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine). OR epirubicin + oxaliplatin + capecitabine OR 4 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel

Group II: Preoperative chemotherapy Active Control 2 Interventions

3 cycles preoperative chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine). OR epirubicin + oxaliplatin + capecitabine OR 4 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel Gastric resection. 3 cycles adjuvant chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine) OR epirubicin + oxaliplatin + capecitabine OR 4 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel

Who Is Running the Clinical Trial?

Australasian Gastro-Intestinal Trials Group

Lead Sponsor

Trials

26

Recruited

8,000+

National Health and Medical Research Council, Australia

Collaborator

Trials

167

Recruited

473,000+

Trans Tasman Radiation Oncology Group

Collaborator

Trials

50

Recruited

16,600+

European Organisation for Research and Treatment of Cancer - EORTC

Collaborator

Trials

417

Recruited

166,000+

NCIC Clinical Trials Group

Collaborator

Trials

190

Recruited

145,000+

Published Research Related to This Trial

The biweekly FLOT chemotherapy regimen, which includes oxaliplatin, leucovorin, fluorouracil, and docetaxel, showed a 57.7% objective response rate in 54 patients with metastatic gastric cancer, indicating its efficacy.

Despite some significant side effects like neutropenia and leukopenia, the treatment demonstrated a favorable safety profile, with only 3.8% of patients experiencing complicated neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Al-Batran, SE., Hartmann, JT., Hofheinz, R., et al.[2022]

Chemotherapy significantly increases survival and improves quality of life in patients with advanced gastric carcinoma compared to supportive measures alone.

Current standard treatments include infusional 5-FU combined with cisplatin or ECF, while newer third-generation combinations with taxanes and irinotecan show similar effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Patient with stomach cancer with metastases. What is the value of chemotherapy?]. Wilke, H., Stahl, M., Vanhoefer, U.[2013]

A patient with HER2- and PD-L1-positive locally advanced gastric carcinoma achieved a pathologic complete response after receiving a neoadjuvant therapy regimen that included toripalimab, Herceptin, and FLOT chemotherapy, followed by surgery.

This case suggests that combining immunotherapy with chemotherapy may be an effective neoadjuvant treatment strategy for gastric carcinoma, but further large-scale phase III clinical trials are needed to confirm the safety and efficacy of such approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toripalimab combined with targeted therapy and chemotherapy achieves pathologic complete response in gastric carcinoma: A case report. Liu, R., Wang, X., Ji, Z., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8025817/

Comparison of Perioperative Chemotherapy versus ... Sixty-seven (76%) patients received PCR, while 21 (24%) patients received PC. The median overall survival of the whole group was 34 months, with ...

2. nature.com nature.com/articles/s41598-024-82807-8

Evaluating survival outcomes and treatment ... Patients who received PC had the highest OS (median 86.80 months, 95% CI 73.40-NE), while chemoradiotherapy in the neoadjuvant and adjuvant ...

3. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-022-09297-7

Preoperative versus postoperative chemo-radiotherapy for ... In conclusion, preoperative chemo-radiotherapy may have better long-term outcomes for locally advanced gastric cancer, compared with post- ...

4. falkfoundation.org falkfoundation.org/en/fgr/detail/preoperative-chemoradiotherapy-for-resectable-gastric-cancer/

Preoperative chemoradiotherapy for resectable gastric ... The median overall survival was 46 months with preoperative chemoradiotherapy and 49 months with perioperative chemotherapy (hazard ratio for death = 1.05; 95% ...

5. dmr.amegroups.org dmr.amegroups.org/article/view/9085/html

Radiotherapy in gastric cancer: does it still play a significant ... Local progression-free survival (PFS) after tumor resection was significantly improved by induction chemoradiotherapy (HR: 0.37; 95% CI: 0.16–0.85). The ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12401422/

a systematic review and meta-analysis - PMC Chemoradiotherapy was associated with higher recurrence-free survival (HR: 0.79, P = 0.004) and slightly improved overall survival (HR: 0.85, P ...

7. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2405195

Preoperative Chemoradiotherapy for Resectable Gastric ... The median overall survival was 46 months with preoperative chemoradiotherapy and 49 months with perioperative chemotherapy (hazard ratio for death, 1.05; 95% ...

8. esmo.org esmo.org/oncology-news/no-survival-benefit-from-adding-preoperative-chemoradiotherapy-to-perioperative-chemotherapy-in-patients-with-resectable-gastric-gej-adenocarcinoma

No Survival Benefit from Adding Preoperative ... The overall incidence of gastrointestinal side-effects was 28% in the preoperative chemoradiotherapy group and 25% in the perioperative ...

9. healio.com healio.com/news/hematology-oncology/20241127/preoperative-chemotherapy-does-not-improve-outcomes-in-resectable-gastric-cancer

Preoperative chemoradiotherapy does not improve ... Preoperative chemoradiotherapy did not improve survival for individuals with resectable gastric cancer. The regimen did produce higher rates ...

10. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-022-10272-5

Safety and short-term outcomes of gastrectomy after ... In patients with AGC, gastrectomy with D2 or D2 + lymphadenectomy after PCIT had comparable short-term oncological outcomes to PCT.