Chemotherapy + Rucaparib for Digestive System Cancers

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Academic and Community Cancer Research United

Must not be taking: Antiretrovirals, PARP inhibitors

Disqualifiers: Pregnancy, HIV, Uncontrolled illness, others

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

Compensation: Varies

Number of Visits: 2

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I/II trial studies the side effects and best dose of liposomal irinotecan and rucaparib when given together with fluorouracil and leucovorin calcium and to see how well they work in treating patients with pancreatic, colorectal, gastroesophageal, or biliary cancer that has spread to other places in the body (metastatic). Chemotherapy drugs, such as liposomal irinotecan, fluorouracil, and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as rucaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Giving liposomal irinotecan and rucaparib together with fluorouracil and leucovorin calcium may work better in treating patients with pancreatic, colorectal, gastroesophageal, or biliary cancer.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you must stop any prior chemotherapy at least 28 days before joining the trial.

What data supports the effectiveness of the drug combination of Chemotherapy + Rucaparib for Digestive System Cancers?

Research shows that combining irinotecan with 5-fluorouracil (5-FU) and leucovorin improves response rates and delays disease progression in colorectal cancer. Additionally, liposomal irinotecan combined with 5-FU and leucovorin has shown positive outcomes in pancreatic cancer, suggesting potential benefits for digestive system cancers. ^{1 2 3 4 5}

Is the combination of chemotherapy drugs including 5-fluorouracil, leucovorin, and irinotecan safe for treating digestive system cancers?

The combination of chemotherapy drugs like 5-fluorouracil, leucovorin, and irinotecan has been studied for various digestive system cancers and is generally considered safe, though it can have manageable side effects. For example, the FOLFIRINOX regimen, which includes these drugs, is known to be more toxic than some alternatives but still safe with manageable side effects. ^{2 6 7 8 9}

What makes the chemotherapy + Rucaparib drug unique for digestive system cancers?

This treatment combines traditional chemotherapy drugs like 5-fluorouracil and leucovorin with rucaparib, a newer drug that targets specific cancer cell mechanisms, potentially offering a novel approach for digestive system cancers compared to standard chemotherapy alone. ^{2 6 10 11 12}

Research Team

Tanios S Bekaii-Saab

Principal Investigator

Academic and Community Cancer Research United

Eligibility Criteria

This trial is for adults with certain metastatic cancers (pancreatic, colorectal, gastroesophageal, or biliary) who've had limited prior treatments. They must have a good performance status and adequate organ function. Pregnant or nursing individuals can't join, nor those with HIV on antiretrovirals, other recent cancers, severe diseases that could interfere with the study, or if they've had specific treatments like PARP inhibitors.

Inclusion Criteria

Placement of an intrauterine device or intrauterine system

Platelet count >= 100,000/mm^3 (obtained =< 21 days prior to registration)

I have gastroesophageal cancer and received only one prior treatment for it in the metastatic stage.

Exclusion Criteria

I cannot swallow.

I have not taken PARPi treatments recently, or it's been over a year since my last dose.

Corrected QT interval (QTc) prolongation > 480 msec, as calculated by either the Bazett or Fridericia formula, as per institutional standard

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase Ia Treatment

Patients receive liposomal irinotecan, leucovorin calcium, and fluorouracil intravenously, and rucaparib orally. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Visits on days 1 and 15 for IV administration

Phase Ib/II Treatment

Patients receive liposomal irinotecan and fluorouracil intravenously, and rucaparib orally. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Visits on days 1 and 15 for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Every 6 months for 3 years

Treatment Details

Interventions

• Fluorouracil
• Leucovorin Calcium
• Liposomal Irinotecan
• Rucaparib

Trial Overview The trial tests liposomal irinotecan and rucaparib combined with fluorouracil and leucovorin calcium to see how well they treat metastatic digestive system cancers. It aims to find the best dose of these drugs together while assessing their effectiveness against tumor growth.

Participant Groups

Group I: Treatment (nal-IRI, leucovorin, fluorouracil, rucaparib) Experimental Treatment 5 Interventions

PHASE Ia: Patients receive liposomal irinotecan IV over 90 minutes, leucovorin calcium IV, and fluorouracil IV over 46 hours on days 1 and 15. Patients also receive rucaparib PO BID on days 4-13 and 18-27. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. PHASE Ib/II: Patients receive liposomal irinotecan IV over 90 minutes and fluorouracil IV over 46 hours on days 1 and 15. Patients also receive rucaparib PO BID on days 4-13 and 18-27. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity.

Fluorouracil is already approved in United States, European Union, Canada for the following indications:

Approved in United States as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Skin cancer

Approved in European Union as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Approved in Canada as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Academic and Community Cancer Research United

Lead Sponsor

Trials

54

Recruited

4,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Irinotecan has been approved for patients with colorectal cancer who do not respond to 5-fluorouracil and has shown effectiveness both alone and in combination with other agents like 5-fluorouracil and leucovorin.

Oxaliplatin, when combined with 5-fluorouracil and leucovorin, results in a higher response rate compared to 5-fluorouracil alone, and it has shown clinical activity even in patients whose disease progressed on previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel chemotherapeutic agents for gastrointestinal cancers. Royce, ME., Pazdur, R.[2019]

The combination of traditional chemotherapy agents like fluorouracil (5FU) with newer drugs such as irinotecan and oxaliplatin has significantly improved treatment effectiveness for colorectal cancer, leading to better patient outcomes.

Emerging targeted therapies are showing promise in reducing toxicity compared to traditional chemotherapy, and their integration into treatment protocols may extend survival rates for metastatic colorectal cancer patients from 2 to potentially 3 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The modern treatment of colorectal cancer. Present and future]. András, C., Farczádi, E., Szántó, J.[2018]

Fluorouracil (5-FU) has been the standard treatment for advanced colorectal cancer for over 40 years, but only a small number of patients show a significant clinical response, highlighting the need for improved therapies.

New oral fluoropyrimidines and combination therapies with oxaliplatin or irinotecan have shown comparable efficacy to traditional 5-FU treatments while reducing side effects like febrile neutropenia and mucositis, suggesting a promising direction for enhancing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colorectal cancer: chemotherapy treatment overview. Royce, ME., Medgyesy, D., Zukowski, TH., et al.[2018]

The study established the maximum tolerated dose (MTD) for the combination treatment NALIRIFOX in patients with metastatic pancreatic ductal adenocarcinoma, with 32 out of 56 patients receiving the MTD, indicating a manageable safety profile despite some patients experiencing severe treatment-related adverse events.

Patients treated with NALIRIFOX showed a median progression-free survival of 9.2 months and overall survival of 12.6 months, suggesting that this treatment regimen may be effective for this difficult-to-treat cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line liposomal irinotecan with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) in pancreatic ductal adenocarcinoma: A phase I/II study. Wainberg, ZA., Bekaii-Saab, T., Boland, PM., et al.[2021]

The FOLFIRINOX regimen, while more toxic than gemcitabine, is considered safe and manageable for treating pancreatic cancer, as evidenced by its use in a case involving steatohepatitis that mimicked liver metastasis.

This case highlights the importance of recognizing atypical adverse events in patients undergoing FOLFIRINOX treatment, which can significantly impact treatment management and decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Steatohepatitis due to FOLFIRINOX regimen in adjuvant pancreas cancer treatment mimicking liver metastasis. Bozkurt Duman, B., Çil, T.[2020]

Recent trials indicate that oral fluoropyrimidine agents like capecitabine (Xeloda) and UFT/leucovorin are as effective as standard intravenous 5-FU in treating advanced colorectal cancer, showing similar response rates and survival outcomes.

These oral agents also have the added benefit of reducing side effects such as neutropenia and stomatitis, making them a promising option for patients undergoing treatment for colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of oral chemotherapy in colorectal cancer. Donehower, RC.[2015]

Oral fluoropyrimidines, such as capecitabine and UFT/LV, offer a more convenient and less toxic alternative to traditional intravenous 5-fluorouracil (5-FU) for treating advanced colorectal cancer (CRC).

Oxaliplatin, with a different mechanism of action than 5-FU, significantly improves response rates and time to disease progression when used in combination with 5-FU and leucovorin in first-line treatment, and is effective even in patients whose cancer has progressed after 5-FU treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel chemotherapy agents for colorectal cancer: oral fluoropyrimidines, oxaliplatin, and raltitrexed. Royce, ME., Hoff, PM., Padzur, R.[2019]

References

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

Treatment outcomes of nanoliposomal irinotecan as second-line chemotherapy after gemcitabine and nab-paclitaxel in metastatic and recurrent pancreatic cancer. [2023]

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

Novel chemotherapeutic agents for gastrointestinal cancers. [2019]

3. Hungary pubmed.ncbi.nlm.nih.gov

[The modern treatment of colorectal cancer. Present and future]. [2018]

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

Colorectal cancer: chemotherapy treatment overview. [2018]

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

Phase II trial of 5-fluorouracil/leucovorin/gemcitabine/cisplatin as second-line treatment in patients with metastatic or recurrent colorectal carcinoma: a cancer therapeutics research group study. [2022]

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

A phase II study of irinotecan, continuous 5-fluorouracil, and leucovorin (FOLFIRI) combination chemotherapy for patients with recurrent or metastatic gastric cancer previously treated with a fluoropyrimidine-based regimen. [2018]

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

First-line liposomal irinotecan with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) in pancreatic ductal adenocarcinoma: A phase I/II study. [2021]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Phase II study of irinotecan, 5-fluorouracil, and leucovorin in relapsed or metastatic colorectal cancer as first-line therapy. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Steatohepatitis due to FOLFIRINOX regimen in adjuvant pancreas cancer treatment mimicking liver metastasis. [2020]

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

Role of oral chemotherapy in colorectal cancer. [2015]

11. Poland pubmed.ncbi.nlm.nih.gov

Survival and relative dose intensity of 5-fluorouracil, oxaliplatin and irinotecan in real-life treatment of metastatic colorectal cancer. [2022]

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

Novel chemotherapy agents for colorectal cancer: oral fluoropyrimidines, oxaliplatin, and raltitrexed. [2019]