IDX-1197 + Chemotherapy for Stomach Cancer

Recruiting at 23 trial locations

Overseen By Minju Hong

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Idience Co., Ltd.

Must not be taking: Cytochrome P3A4, UGT1A1 inhibitors

Disqualifiers: Brain metastasis, Uncontrolled illness, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 12 months

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the safety and effectiveness of a new drug, IDX-1197 (also known as Venadaparib or NOV1401), when combined with chemotherapy treatments XELOX or irinotecan for advanced stomach cancer. Researchers seek to determine patient tolerance and the optimal dosage for this combination. The study is open to individuals with advanced or recurrent stomach cancer, particularly if the cancer is located in the stomach's upper part or the gastroesophageal junction. Suitable participants include those who have either never received treatment for their cancer or have undergone two or more rounds of chemotherapy. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial requires that you stop using any medications that are cytochrome P3A4 inhibitors or inducers, as well as strong UGT1A1 inhibitors. If you're taking these, you may need to stop or switch them before participating.

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

Research shows that IDX-1197, the treatment tested in this trial, belongs to a group of drugs called PARP inhibitors. The FDA has approved these drugs for treating other cancers like ovarian and breast cancer, indicating a known safety record. However, since IDX-1197 is still under study, its specific safety in humans remains under evaluation.

Irinotecan, another treatment in the trial, is already used for various cancers. It is effective but can cause serious side effects, requiring careful monitoring. Previous studies have highlighted the importance of managing its use to prevent severe reactions.

XELOX, a combination of capecitabine and oxaliplatin, is generally considered safe for patients with advanced stomach cancer. Research has shown it to be effective, with manageable side effects.

Participants should know that while these treatments have shown promise, they can also cause side effects. Discussing with the trial team can provide more personalized safety information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

IDX-1197 is unique because it targets a specific enzyme called PARP, which plays a role in cancer cell repair, making it different from the standard chemotherapy options like 5-FU or cisplatin used for stomach cancer. Researchers are excited because IDX-1197, combined with chemotherapy regimens like Irinotecan and XELOX, might enhance the effectiveness of treatment by preventing cancer cells from repairing themselves. This dual approach could potentially increase the treatment's success rate and offer a new hope for patients with stomach cancer.

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

This trial will evaluate IDX-1197, a new treatment that targets cancer cells by blocking certain enzymes, in combination with chemotherapy. Studies have shown promising results for IDX-1197, especially for patients with specific genetic changes. Participants in this trial may receive IDX-1197 alongside either Irinotecan or XELOX. In some trials, Irinotecan demonstrated response rates of up to 43% for advanced stomach cancer. XELOX, a combination of capecitabine and oxaliplatin, showed a 62.2% response rate in patients with advanced stomach cancer. These findings suggest that the treatments being studied could benefit those with advanced stomach cancer. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced gastric cancer, including tumors at the gastroesophageal junction or upper stomach. Group 1 includes those who haven't had treatment before, while Group 2 has had two or more rounds of chemotherapy. Participants must be relatively healthy and active (ECOG ≤1) and have at least one measurable tumor. People with HIV, hepatitis B/C, heart issues, uncontrolled illnesses like diabetes or infections needing IV antibiotics can't join.

Inclusion Criteria

I have advanced stomach cancer and have had at least 2 rounds of chemotherapy.

I am fully active or can carry out light work.

I have at least one tumor that can be measured or evaluated.

Exclusion Criteria

I have no ongoing major side effects from previous treatments.

My heart's electrical activity is abnormal, or I have a family history of long QT syndrome.

I have been diagnosed with myelodysplastic syndrome or acute myeloid leukemia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive IDX-1197 in combination with XELOX or Irinotecan to determine the MTD and RP2D

Up to 12 months

Regular visits as per dose escalation protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• IDX-1197
• Irinotecan
• XELOX

Trial Overview The study tests IDX-1197 in combination with either XELOX (a mix of capecitabine and oxaliplatin) or irinotecan to see how safe they are together and to find the best doses for treating advanced gastric cancer. It's an early-phase trial where everyone knows what treatment they're getting (open-label).

How Is the Trial Designed?

Group I: Group 2 Experimental Treatment 1 Intervention

Group II: Group 1 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Idience Co., Ltd.

Lead Sponsor

Trials

4

Recruited

280+

Published Research Related to This Trial

Intraperitoneal paclitaxel (IP-PTX) combined with capecitabine and oxaliplatin (XELOX) significantly improved overall survival (14.6 months) and progression-free survival (9.5 months) in patients with gastric cancer peritoneal metastases compared to standard systemic chemotherapy (10.6 months OS and 4.4 months PFS).

In patients who responded well to the treatment, conversion surgery was performed in 36.1% of cases, leading to a median overall survival of 24.2 months, indicating that IP-PTX with XELOX not only enhances survival but also allows for surgical intervention in select patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases. Chia, DKA., Sundar, R., Kim, G., et al.[2022]

The recommended dose of intraperitoneal docetaxel (100 mg/m2) combined with systemic capecitabine and cisplatin showed promising efficacy in advanced gastric cancer patients with peritoneal metastasis, resulting in a median progression-free survival of 11.0 months and overall survival of 15.1 months.

While the treatment was effective, the most common severe side effects included neutropenia (38.6%) and abdominal pain (30.8%), with abdominal pain increasing in later treatment cycles, suggesting a need for dose adjustments to manage this toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of a combination of capecitabine, cisplatin, and intraperitoneal docetaxel (XP ID) in advanced gastric cancer patients with peritoneal metastasis. Cho, H., Ryu, MH., Kim, KP., et al.[2018]

The combination of irinotecan, epirubicin, and capecitabine has shown an acceptable toxicity profile in an open-label phase I study involving patients with metastatic adenocarcinomas, indicating it may be a safe treatment option.

The study is still ongoing, as the dose-limiting toxicity has not yet been reached, and further investigations will determine the optimal sequencing of the regimen to enhance clinical efficacy in treating upper gastrointestinal malignancies and breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan, epirubicin, and capecitabine in metastatic adenocarcinomas: preliminary results of a phase I study. Becerra, CR.[2018]

In a study involving six patients with locally advanced gastric cancer, the neoadjuvant chemotherapy regimen of capecitabine and oxaliplatin (G-XELOX) was found to be feasible and had acceptable toxicity, with no treatment-related deaths reported.

Out of the five patients who underwent surgical resection after treatment, four achieved pathological down-staging, indicating a positive response to the neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Neoadjuvant Chemotherapy with Capecitabine and Oxaliplatin for Locally Advanced Gastric Cancer. Satake, H., Kondo, M., Mizumoto, M., et al.[2022]

The combination of irinotecan and docetaxel showed some anti-tumor activity in patients with advanced gastric cancer, achieving an overall response rate of 20.4% in a study of 49 patients, but the treatment was associated with significant toxicity.

Due to high rates of severe side effects, including neutropenia and febrile neutropenia, the combination therapy is not considered feasible as a second-line treatment for patients who have already failed prior chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of irinotecan and docetaxel combination chemotherapy for patients with previously treated metastatic or recurrent advanced gastric cancer. Sym, SJ., Chang, HM., Kang, HJ., et al.[2018]

In a study of 141 patients with locally advanced rectal cancer, the combination of capecitabine and oxaliplatin (Xelox) during volumetric modulated arc therapy (VMAT) was found to be feasible and well tolerated, with a low incidence of severe side effects (only 9.9% for hematologic and 16.3% for non-hematologic adverse events).

The treatment resulted in a complete resection rate of 100% and a pathological complete response (pCR) rate of 32.6%, indicating effective tumor reduction and down-staging, which supports the use of Xelox in preoperative chemoradiotherapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Feasibility study on Xelox (capecitabine plus oxapliplatin) in the volumetric modulated arc therapy (VMAT)-based preoperative chemoradiotherapy for locally advanced rectal cancer]. Xiao, L., Huang, R., You, K., et al.[2020]

Capecitabine and irinotecan, when used together, show promising response rates and manageable toxicities in patients with metastatic colorectal cancer, based on early-phase European trials.

Upcoming phase III trials will further evaluate the effectiveness of the capecitabine/irinotecan regimen compared to standard treatments, involving around 700 patients, which will help clarify its role in colorectal cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine/irinotecan in colorectal cancer: European early-phase data and planned trials. Kerr, D.[2018]

The combination of docetaxel (DTX) and irinotecan (CPT-11) can be safely administered biweekly to patients with advanced breast cancer (BC) and non-small-cell lung cancer (NSCLC), with dose escalation reaching 80 mg/m² for DTX and 100 mg/m² for CPT-11 supported by filgrastim.

The treatment showed promising efficacy, with an overall response rate of 51% across 41 patients, including a 59% response rate in BC patients and a 36% response rate in NSCLC patients, indicating potential for further phase II studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biweekly docetaxel-irinotecan with filgrastim support in pretreated breast and non-small-cell lung cancer patients. A phase I study. Frasci, G., Comella, P., Thomas, R., et al.[2018]

In a study of 32 patients with metastatic gastric cancer who had prior chemotherapy, the combination of irinotecan (CPT-11) and cisplatin (CDDP) showed a partial response rate of 28% and a median overall survival of 283 days, indicating its potential efficacy in this patient population.

The treatment was generally well-tolerated, with significant adverse effects like grade 4 neutropenia occurring in 69% of patients, but no treatment-related deaths were reported, suggesting a manageable safety profile for this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination chemotherapy with irinotecan and cisplatin in pretreated patients with unresectable or recurrent gastric cancer. Ueda, S., Hironaka, S., Boku, N., et al.[2019]

The modified XELOX regimen, using oxaliplatin and capecitabine, showed a 39.1% overall tumor response rate in 49 patients with advanced gastric cancer, indicating its efficacy as a first-line treatment.

The treatment was associated with manageable safety concerns, with the most common severe side effects being anemia and hand-foot syndrome, suggesting that the regimen is practical for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified biweekly oxaliplatin and capecitabine for advanced gastric cancer: a retrospective analysis from a medical center. Kuo, YC., Liu, HT., Lin, YL., et al.[2018]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4045

Efficacy of venadaparib plus irinotecan in homologous ... Venadaparib in combination with irinotecan demonstrated promising efficacy in patients with mGC, particularly those with HRD gene mutations.

2. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04725994/

Clinical Trial: NCT04725994 This is an open-label, Phase 1b study to evaluate the safety and tolerability of IDX-1197 and determine the MTD and RP2D in combination with XELOX or ...

3. withpower.com withpower.com/trial/phase-1-stomach-neoplasms-5-2021-6c40e

IDX-1197 + Chemotherapy for Stomach Cancer Research shows that the combination of capecitabine and irinotecan has been effective in treating colorectal cancer, and irinotecan with docetaxel has shown ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9978881/

Venadaparib Is a Novel and Selective PARP Inhibitor with ... Venadaparib specifically inhibits PARP-1 and -2 enzymes. Oral administration of venadaparib HCl at doses above 12.5 mg/kg significantly reduced tumor growth in ...

5. nature.com nature.com/articles/d43747-020-01104-1

Idience: developing selective and potent PARP inhibitor ... Developing a better PARP inhibitor​​ Idience's focus on anticancer drugs that could transform patient quality of life is exemplified by its lead asset IDX-1197, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04725994

Study to Assess the Safety, Tolerability, and Efficacy of IDX ... Study to Assess the Safety, Tolerability, and Efficacy of IDX-1197 in Combination with XELOX or Irinotecan in Patients with Advanced Gastric Cancer.