BI 905711 + Chemotherapy for Gastrointestinal Cancer

Recruiting at 9 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must be taking: Chemotherapy, Bevacizumab

Must not be taking: Anti-angiogenics, Anti-EGFR

Disqualifiers: Irinotecan, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 4

Duration: Up to 54 weeks

13 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is for adults with advanced colorectal or pancreatic cancer. It tests a new drug, BI 905711, combined with standard treatments to find the safest dose and see if it helps shrink tumors. Patients receive the treatment regularly and are monitored for health changes and tumor size.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had certain cancer treatments recently, like specific drugs or radiation therapy, before starting the trial.

What data supports the effectiveness of the drug combination BI 905711 + Chemotherapy for gastrointestinal cancer?

Research shows that combinations including irinotecan, 5-fluorouracil, and folinic acid (components of FOLFIRI) have been effective in treating advanced gastric and colorectal cancers, with improved survival rates and response rates over other treatments. These findings suggest that similar combinations could be beneficial for gastrointestinal cancers. ^{1 2 3 4 5}

Is the combination of BI 905711 and chemotherapy safe for humans?

The combination of chemotherapy drugs like FOLFIRI and bevacizumab (also known as Avastin) has been studied for safety in patients with metastatic colorectal cancer. These studies show that while the treatment can be effective, it may also lead to significant side effects such as neutropenia (low white blood cell count) and diarrhea, especially at higher doses. Safety profiles can vary based on genetic factors, and some trials were stopped due to unacceptable toxicity levels. ^{6 7 8 9 10}

What makes the drug BI 905711 + FOLFIRI unique for gastrointestinal cancer?

The combination of BI 905711 with FOLFIRI is unique because it integrates a novel agent, BI 905711, with an established chemotherapy regimen (FOLFIRI) that includes irinotecan, 5-fluorouracil, and folinic acid, which have shown efficacy in treating various gastrointestinal cancers. This combination may offer a new therapeutic option by potentially enhancing the effectiveness of standard chemotherapy. ^{3 5 11 12 13}

Eligibility Criteria

Inclusion Criteria

Of legal adult age (according to local legislation) at screening.

Eastern Cooperative Oncology Group (ECOG) performance status ≤1.

Signed and dated written informed consent in accordance with International Council of Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.

Exclusion Criteria

You have taken any non-experimental drugs, like bevacizumab, ramucirumab, aflibercept, cetuximab, or panitumumab, within the past 14 days.

- Currently enrolled in another investigational device or drug trial. Patients who are in follow-up/observation for another clinical trial are eligible.

- Radiation therapy within 4 weeks prior to start of treatment. However, palliative radiotherapy for symptomatic metastasis is allowed if completed within 2 weeks prior to start of treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants with colorectal cancer receive BI 905711 combined with chemotherapy and bevacizumab to find the highest dose they can tolerate.

Up to 35 days

Every 2 weeks

Treatment

Participants receive BI 905711, chemotherapy, and bevacizumab every 2 weeks to test if BI 905711 makes tumors shrink.

Up to 54 weeks

Every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Bevacizumab
• BI 905711
• FOLFIRI

Participant Groups

Group I: 1.2 mg/kg BI 905711 + FOLFIRI + bevacizumab Experimental Treatment 3 Interventions

Patients with colorectal adenocarcinoma (CRC) received a single administration of 1.2 mg/kg of BI 905711 intravenously on Day 3 of each 14-day cycle. Patients also received FOLFIRI (irinotecan: 180 mg/m2 over 1.5 hours (hrs), leucovorin: 400 mg/m2 (in Japan: levoleucovorin: 200 mg/m2) over 2 hrs, fluorouracil: 400 mg/m2 bolus or 2400 mg/m2 46 hrs continuous infusion) in combination with bevacizumab, 5 mg/kg over 30 minutes (min) intravenously on Day 1 of each 14-day cycle.

Group II: 0.6 mg/kg BI 905711 + FOLFIRI + bevacizumab Experimental Treatment 3 Interventions

Patients with colorectal adenocarcinoma (CRC) received a single administration of 0.6 milligrams (mg) / kilograms (kg) of BI 905711 intravenously on Day 3 of each 14-day cycle. Patients also received FOLFIRI (irinotecan: 180 mg/squaremeters (m2) over 1.5 hours (hrs), leucovorin: 400 mg/m2 (in Japan: levoleucovorin: 200 mg/m2) over 2 hrs, fluorouracil: 400 mg/m2 bolus or 2400 mg/m2 46 hrs continuous infusion) in combination with bevacizumab, 5 mg/kg over 30 minutes (min) intravenously on Day 1 of each 14-day cycle.

Group III: FOLFIRI + bevacizumab Active Control 2 Interventions

Patients with colorectal adenocarcinoma (CRC) received FOLFIRI (irinotecan: 180 mg/m2 over 1.5 hours (hrs), leucovorin \[or levoleucovorin\]: 400 mg/m2 (in Japan: levoleucovorin: 200 mg/m2) over 2 hrs, fluorouracil: 400 mg/m2 bolus or 2400 mg/m2 46 hrs continuous infusion) in combination with bevacizumab, 5 mg/kg over 30 minutes (min) intravenously on Day 1 of each 14-day cycle.

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Findings from Research

In a study of 115 patients with advanced gastric cancer, the combination of irinotecan, 5-fluorouracil (5-FU), and folinic acid (FA) showed a higher overall response rate of 42.4% and a median survival time of 10.7 months compared to 32.1% and 6.9 months for the irinotecan/cisplatin combination.

The irinotecan/5-FU/FA regimen had a better safety profile, with significantly lower rates of severe neutropenia (27% vs. 65.7%) compared to irinotecan/cisplatin, making it the preferred choice for further investigation in a phase III trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study. Pozzo, C., Barone, C., Szanto, J., et al.[2020]

Irinotecan has been shown to significantly prolong survival in patients with 5-FU-resistant colorectal cancer compared to best supportive care or 5-FU-based chemotherapy, based on Phase III studies.

Combining irinotecan with other treatments, such as raltitrexed or oral fluoropyrimidines, has shown promising results in terms of safety and efficacy, with response rates exceeding 30% and median survival benefits in various cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical advances with topoisomerase I inhibitors in gastrointestinal malignancies. Armand, JP., Cunningham, D., van Cutsem, E., et al.[2019]

In a study of 69 Asian patients with metastatic colorectal cancer, the combination of FOLFOXIRI and bevacizumab resulted in a high progression-free survival (PFS) rate of 75.2% at 10 months, indicating its effectiveness as a first-line treatment.

However, this regimen was associated with significant adverse events, particularly high rates of neutropenia (72.5%) and hypertension (34.8%), highlighting the need for careful monitoring, especially in patients with specific UGT1A1 genetic polymorphisms that increase the risk of severe neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicenter Clinical Phase II Study of FOLFOXIRI Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer: QUATTRO Study. Oki, E., Kato, T., Bando, H., et al.[2022]

The maximum tolerated dose (MTD) of irinotecan for patients with the UGT1A1 *1/*1 genotype is 310 mg/m2, while for those with the *1/*28 genotype, it is 260 mg/m2, indicating that genetic differences can influence drug tolerance in metastatic colorectal cancer treatment.

Bevacizumab does not significantly affect the pharmacokinetics of irinotecan, suggesting that the dosing adjustments based on genotype can be made without concern for altered drug metabolism due to this additional treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genotype-Guided Dosing Study of FOLFIRI plus Bevacizumab in Patients with Metastatic Colorectal Cancer. Toffoli, G., Sharma, MR., Marangon, E., et al.[2022]

The modified 5-fluorouracil/leucovorin/irinotecan (mFOLFIRI) regimen showed a response rate of 29.7% and a clinical benefit rate of 57.2% in 91 patients with advanced gastric cancer, indicating its efficacy as a second-line treatment.

Despite its effectiveness, the mFOLFIRI regimen was associated with significant adverse events, including neutropenia in 18.7% of patients, highlighting the need for careful monitoring and potential dose modifications during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified 5-fluorouracil/leucovorin/irinotecan as a feasible and efficacious second-line chemotherapeutic regimen in advanced gastric cancers. Ramaswamy, A., Ostwal, V., Gupta, K., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study. [2020]

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

Aflibercept in Combination With FOLFIRI as First-line Chemotherapy in Patients With Metastatic Colorectal Cancer (mCRC): A Phase II Study (FFCD 1302). [2021]

3. England pubmed.ncbi.nlm.nih.gov

Clinical advances with topoisomerase I inhibitors in gastrointestinal malignancies. [2019]

4. England pubmed.ncbi.nlm.nih.gov

A phase II study of irinotecan with bi-weekly, low-dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFIRI) as salvage therapy for patients with advanced or metastatic gastric cancer. [2022]

5. France pubmed.ncbi.nlm.nih.gov

[Irinotecan in combination for colon cancer]. [2018]

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

A Multicenter Clinical Phase II Study of FOLFOXIRI Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer: QUATTRO Study. [2022]

7. Spain pubmed.ncbi.nlm.nih.gov

Efficacy and safety of high doses of irinotecan in patients with metastatic colorectal cancer treated with the FOLFIRI regimen based on the UGT1A1 genotype: A systematic review. [2022]

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

Genotype-Guided Dosing Study of FOLFIRI plus Bevacizumab in Patients with Metastatic Colorectal Cancer. [2022]

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

High-Dose FOLFIRI plus Bevacizumab in the Treatment of Metastatic Colorectal Cancer Patients with Two Different UGT1A1 Genotypes: FFCD 0504 Study. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Irinotecan plus folinic acid/continuous 5-fluorouracil as simplified bimonthly FOLFIRI regimen for first-line therapy of metastatic colorectal cancer. [2018]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Third-Line Chemotherapy with Irinotecan plus 5-Fluorouracil in Caucasian Metastatic Gastric Cancer Patients. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

Salvage chemotherapy of biweekly irinotecan plus S-1 (biweekly IRIS) in previously treated patients with advanced gastric cancer. [2023]

13. India pubmed.ncbi.nlm.nih.gov

Modified 5-fluorouracil/leucovorin/irinotecan as a feasible and efficacious second-line chemotherapeutic regimen in advanced gastric cancers. [2022]