IDX-1197 + Chemotherapy for Stomach Cancer

Recruiting at 16 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

Trial Summary

What is the purpose of this trial?

This is an open-label, Phase 1b/2a study to evaluate the safety and tolerability of IDX-1197 and determine the MTD and RP2D in combination with XELOX or irinotecan in patients with advanced gastric cancer.

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.

What data supports the effectiveness of the drug combination IDX-1197, Venadaparib, NOV1401, Irinotecan, Camptosar, CPT-11, XELOX, Capecitabine/Oxaliplatin 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 promise in advanced gastric cancer. Additionally, capecitabine and oxaliplatin have been studied for locally advanced gastric cancer, suggesting potential benefits for stomach cancer treatment. ^{1 2 3 4 5}

What safety data exists for IDX-1197 + Chemotherapy for Stomach Cancer?

The combination of irinotecan (Camptosar) and capecitabine (Xeloda) has shown manageable toxicities in early-phase trials for colorectal cancer. Additionally, a modified XELOX regimen (capecitabine plus oxaliplatin) was evaluated for advanced gastric cancer, indicating a practical safety profile in clinical practice. ^{1 3 6 7 8}

What makes the drug IDX-1197 + Chemotherapy unique for stomach cancer?

The drug IDX-1197 combined with chemotherapy is unique because it includes Venadaparib (IDX-1197), which is not commonly used in standard treatments for stomach cancer. This combination aims to enhance the effectiveness of chemotherapy agents like Irinotecan and XELOX (Capecitabine/Oxaliplatin), potentially offering a novel approach for patients with this condition. ^{4 5 7 9 10}

Eligibility Criteria

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 advanced or recurrent stomach cancer that has not been treated yet.

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

References

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

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

2. Greece pubmed.ncbi.nlm.nih.gov

Phase I Study of Neoadjuvant Chemotherapy with Capecitabine and Oxaliplatin for Locally Advanced Gastric Cancer. [2022]

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

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

4. Germany 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. [2018]

5. Germany 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. [2018]

6. China 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]. [2020]

7. United States 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. [2022]

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

Modified biweekly oxaliplatin and capecitabine for advanced gastric cancer: a retrospective analysis from a medical center. [2018]

9. Japan 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. [2018]

10. Japan pubmed.ncbi.nlm.nih.gov

Combination chemotherapy with irinotecan and cisplatin in pretreated patients with unresectable or recurrent gastric cancer. [2019]