BI 765883 Alone or With Chemotherapy for Pancreatic Cancer

Recruiting at 19 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must not be taking: Gemcitabine, Paclitaxel

Disqualifiers: Neurologic, Psychiatric, Cardiovascular, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 350 days

68 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is open to adults with advanced pancreatic cancer for whom previous treatment was not successful or no treatment exists. The purpose of this study is to find the highest dose of BI 765883 that people with advanced pancreatic cancer can tolerate when taken alone or together with chemotherapy. Another purpose is to check whether BI 765883 helps people with advanced pancreatic cancer. In this study, BI 765883 is given to humans for the first time. Participants receive either BI 765883 alone or BI 765883 in combination with chemotherapy. Participants can stay in the study as long as they benefit from treatment and can tolerate it. At study visits, doctors collect information on any health problems of the participants and check the severity of participants' cancer.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you have had prior radiotherapy or systemic therapy within 14 days before starting the trial.

What data supports the effectiveness of the drug BI 765883 alone or with chemotherapy for pancreatic cancer?

Gemcitabine, a component of the treatment, has been shown to improve survival in some patients with advanced pancreatic cancer, although the overall survival benefit is modest. Additionally, combining gemcitabine with other drugs, like capecitabine, has led to better survival outcomes in certain cases. ^{1 2 3 4 5}

What safety data exists for BI 765883 and related treatments in humans?

The combination of nab-paclitaxel (also known as Abraxane or albumin-bound paclitaxel) and gemcitabine (also known as Gemzar) has shown an acceptable safety profile in patients with advanced solid tumors, including pancreatic cancer. This suggests that these drugs, when used together, are generally safe for human use in similar conditions. ^{4 6 7 8 9}

What makes the drug BI 765883 unique for treating pancreatic cancer?

The drug BI 765883 is unique because it is being studied both alone and in combination with chemotherapy for pancreatic cancer, which may offer a new approach compared to standard chemotherapy regimens like FOLFIRINOX or gemcitabine-based treatments. This trial could provide insights into its effectiveness and potential benefits over existing therapies. ^{10 11 12 13 14}

Eligibility Criteria

Adults with advanced pancreatic cancer who have not had success with previous treatments or for whom no treatment exists. They must be able to provide informed consent, have a life expectancy of at least 3 months, and agree to use effective birth control. A confirmed diagnosis of Pancreatic ductal adenocarcinoma (PDAC) is required, along with an ECOG performance status ≤1.

Inclusion Criteria

I have signed and understand the consent form for this trial.

6. Life expectancy ≥3 months in the opinion of the investigator 7. Archived tumor tissue from a tissue core biopsy (e.g. paraffin-embedded formalin-fixed tissue blocks), OR fresh tumor tissue available for retrospective biomarker analysis; in both cases, a minimum of at least two core needle biopsies (18 gauge or greater) is required. Only non-significant risk procedures per the investigator's judgment will be used to obtain any biopsies specified in this study in cases where a fresh tumor biopsy is required.

I am using or willing to use effective birth control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BI 765883 alone or in combination with chemotherapy. The treatment continues as long as participants benefit and can tolerate it.

Up to 350 days

Regular study visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• BI 765883
• gemcitabine
• nab-paclitaxel

Trial Overview The trial is testing the highest tolerable dose of BI 765883 alone or combined with chemotherapy in treating advanced pancreatic cancer. It's the first time BI 765883 is given to humans, aiming to check its effectiveness against this type of cancer.

Participant Groups

Group I: BI 765883 escalation arm Experimental Treatment 1 Intervention

phase Ia

Group II: BI 765883 + gemcitabine + nab-paclitaxel expansion arm Experimental Treatment 3 Interventions

phase Ib

Group III: BI 765883 + gemcitabine + nab-paclitaxel escalation arm Experimental Treatment 3 Interventions

phase Ia

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Findings from Research

The ESPAC-4 trial demonstrated that combining gemcitabine with capecitabine significantly improves 5-year survival rates for patients undergoing surgery for pancreatic cancer compared to gemcitabine alone.

This finding is expected to change the standard treatment approach for pancreatic cancer patients who are eligible for surgery, highlighting the importance of combination therapy in improving outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic Cancer Survival Increases with Chemo Combo. [2022]

In a study of 985 patients with pancreatic adenocarcinoma, completing all six cycles of adjuvant chemotherapy significantly improved overall survival rates, with a hazard ratio of 0.516, indicating a strong benefit for those who completed the full course.

The timing of chemotherapy initiation did not affect overall survival for the entire group, suggesting that delaying treatment for up to 12 weeks post-surgery is acceptable to allow for recovery, particularly for patients who may not complete the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study. Valle, JW., Palmer, D., Jackson, R., et al.[2022]

Chemotherapy for advanced pancreatic cancer shows low overall activity but can provide a slight survival benefit and improve quality of life for some patients, as indicated by a systematic review of eight small randomized trials.

While gemcitabine is an approved treatment in some countries, there is no standard chemotherapy regimen established, and conclusive evidence for the use of adjuvant chemotherapy remains lacking due to the small number of patients in relevant trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in the treatment of cancer of the pancreas. Glimelius, B.[2022]

In a phase II study involving 45 patients with unresectable or metastatic pancreatic cancer, the combination of irinotecan and gemcitabine showed promising efficacy, with a 20% overall response rate and a median survival of 5.7 months.

The treatment was well tolerated, with severe toxicities being rare, primarily consisting of low rates of grade 4 neutropenia and vomiting, indicating a favorable safety profile for this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor marker responses in patients with previously untreated advanced pancreatic cancer. Rocha Lima, CM., Savarese, D., Bruckner, H., et al.[2022]

Despite gemcitabine being the first-line treatment for advanced pancreatic cancer for 15 years, median survival times have not significantly improved, with a pooled median survival of only 6.15 months from 21 trials involving 6348 patients.

Only one trial showed a significant improvement in survival when combining a novel agent with gemcitabine, highlighting the need for further research into new treatments to enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled survival and response data from phase III randomized controlled trials for gemcitabine-based regimes in the treatment of advanced pancreatic cancer. Arshad, A., Al-Leswas, D., Al-Taan, O., et al.[2022]

Dovitinib, when combined with gemcitabine and capecitabine, was found to be safe at a recommended dose of 300 mg daily, with manageable side effects such as fatigue and neutropenia in a study involving 29 patients with advanced pancreatic and biliary tract cancers.

The combination treatment showed promising efficacy, with partial responses observed in 5 patients, indicating potential benefits for those suffering from advanced pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of the FGFR/VEGFR Inhibitor Dovitinib With Gemcitabine and Capecitabine in Advanced Solid Tumor and Pancreatic Cancer Patients. Ma, WW., Xie, H., Fetterly, G., et al.[2022]

Itacitinib, a selective JAK1 inhibitor, combined with nab-paclitaxel and gemcitabine, showed an acceptable safety profile and clinical activity in patients with advanced solid tumors, including pancreatic cancer, with a 24% overall response rate across various doses.

The study indicated that while itacitinib was tolerated at lower doses, treatment-related toxicities such as neutropenia and fatigue were common, leading to dose adjustments; however, the study was terminated early due to negative results from a related phase III trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. Beatty, GL., Shahda, S., Beck, T., et al.[2022]

In a randomized phase II trial involving 51 patients with borderline-resectable pancreatic cancer, neoadjuvant chemotherapy using either FOLFIRINOX or GEM/nab-PTX was found to be feasible and well tolerated, achieving an R0 resection rate of 67.4%.

The study reported a 3-year overall survival rate of 54.7% and a median survival time of 39.4 months, indicating that neoadjuvant chemotherapy can provide significant survival benefits despite a notable incidence of adverse events (45.1% experienced grade >3 adverse events).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a Phase II Study on the Use of Neoadjuvant Chemotherapy (FOLFIRINOX or GEM/nab-PTX) for Borderline-resectable Pancreatic Cancer (NUPAT-01). Yamaguchi, J., Yokoyama, Y., Fujii, T., et al.[2023]

In a phase II study involving 7 patients with advanced pancreatic cancer, the combination of panobinostat and bortezomib showed no treatment responses and was associated with significant early treatment-related toxicity, leading to the study's suspension.

The median progression-free survival for patients was only 2.1 months, with severe side effects such as thrombocytopenia occurring in 57% of patients and diarrhea in 29%, indicating that this treatment regimen is not effective or safe for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of panobinostat and bortezomib in patients with pancreatic cancer progressing on gemcitabine-based therapy. Wang, H., Cao, Q., Dudek, AZ.[2022]

In a phase 2 study involving 36 patients with advanced pancreatic cancer, the combination of cisplatin and gemcitabine showed promising activity, with 62.8% of patients achieving stable disease or better, and a median survival of 9.5 months.

While significant hematological toxicities were observed, they were mostly asymptomatic, and the treatment regimen demonstrated potential for improving survival, warranting further investigation in a larger randomized controlled trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of weekly cisplatin and gemcitabine in patients with advanced pancreatic cancer: is this a strategy still worth pursuing? Clayton, AJ., Mansoor, AW., Jones, ET., et al.[2022]

Gemcitabine has changed the perception of pancreatic cancer treatment, showing good tolerability and low side effects, making it a viable option for combination therapies with drugs like cisplatin and 5-fluorouracil.

Combination regimens with gemcitabine and cisplatin have shown response rates between 11.4% and 58% and median survival times of 7.4 to 10 months, while gemcitabine with 5-FU has lower response rates and survival times, indicating the need for further optimization of treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine-based combination treatment of pancreatic cancer. Heinemann, V.[2022]

In a study of 190 patients with advanced pancreatic cancer, the three chemotherapy regimens (CapOx, CapGem, and mGemOx) showed similar efficacy, with median progression-free survival rates of 4.2 months, 5.7 months, and 3.9 months, respectively.

While all regimens had manageable toxicity profiles, the Gem-containing treatments (CapGem and mGemOx) were associated with higher rates of severe hematological toxicities, indicating that while effective, they may require closer monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine plus oxaliplatin (CapOx) versus capecitabine plus gemcitabine (CapGem) versus gemcitabine plus oxaliplatin (mGemOx): final results of a multicenter randomized phase II trial in advanced pancreatic cancer. Boeck, S., Hoehler, T., Seipelt, G., et al.[2022]

Pancreatic cancer, despite being a small percentage of overall cancer cases, is highly lethal, with only 10%-15% of patients having tumors that can be surgically removed, highlighting the need for effective treatment strategies.

Current treatment for locally advanced pancreatic cancer typically involves chemotherapy combined with radiation, but there is ongoing debate about the best chemotherapy agent to use, with research exploring biologically targeted therapies to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Locally advanced pancreatic cancer: current therapeutic approach. Cardenes, HR., Chiorean, EG., Dewitt, J., et al.[2006]

Neoadjuvant chemotherapy using S-1 and gemcitabine significantly improves survival rates for patients with resectable pancreatic cancer compared to immediate surgery, while maintaining similar perioperative outcomes.

Japanese guidelines now recommend neoadjuvant chemotherapy for resectable pancreatic cancer due to its ability to increase R0 resection rates, although identifying predictive markers for chemotherapy response is crucial to avoid missing surgical opportunities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Present status and perspective of perioperative chemotherapy for patients with resectable pancreatic cancer in Japan. Yamada, Y.[2022]

References

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

Pancreatic Cancer Survival Increases with Chemo Combo. [2022]

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

Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

Chemotherapy in the treatment of cancer of the pancreas. [2022]

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

Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor marker responses in patients with previously untreated advanced pancreatic cancer. [2022]

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

Pooled survival and response data from phase III randomized controlled trials for gemcitabine-based regimes in the treatment of advanced pancreatic cancer. [2022]

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

A Phase Ib Study of the FGFR/VEGFR Inhibitor Dovitinib With Gemcitabine and Capecitabine in Advanced Solid Tumor and Pancreatic Cancer Patients. [2022]

7. England pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. [2022]

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

Results of a Phase II Study on the Use of Neoadjuvant Chemotherapy (FOLFIRINOX or GEM/nab-PTX) for Borderline-resectable Pancreatic Cancer (NUPAT-01). [2023]

9. Greece pubmed.ncbi.nlm.nih.gov

Phase II study of panobinostat and bortezomib in patients with pancreatic cancer progressing on gemcitabine-based therapy. [2022]

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

A phase II study of weekly cisplatin and gemcitabine in patients with advanced pancreatic cancer: is this a strategy still worth pursuing? [2022]

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

Gemcitabine-based combination treatment of pancreatic cancer. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Capecitabine plus oxaliplatin (CapOx) versus capecitabine plus gemcitabine (CapGem) versus gemcitabine plus oxaliplatin (mGemOx): final results of a multicenter randomized phase II trial in advanced pancreatic cancer. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Locally advanced pancreatic cancer: current therapeutic approach. [2006]

14. Japan pubmed.ncbi.nlm.nih.gov

Present status and perspective of perioperative chemotherapy for patients with resectable pancreatic cancer in Japan. [2022]