Chemotherapy + Rucaparib for Digestive System Cancers

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for individuals with certain metastatic digestive system cancers, such as pancreatic, colorectal, gastroesophageal, or biliary cancers. It combines chemotherapy drugs, including fluorouracil, leucovorin calcium, and liposomal irinotecan, with rucaparib, a medication that blocks a protein aiding cancer cell repair. The trial aims to determine the optimal dose and assess the effectiveness of this combination. Suitable candidates have metastatic pancreatic, colorectal, gastroesophageal, or biliary cancer with limited prior treatments. This trial may offer a new treatment option if previous ones have been ineffective. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing an opportunity to be among the first to receive this new combination therapy.

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.

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

Research has shown that the combination of liposomal irinotecan, fluorouracil, and leucovorin calcium is generally safe and well-tolerated. One study found this mix to be a practical treatment option. Some patients reported side effects like tiredness and diarrhea, but these were manageable for most.

Rucaparib, a medication used in this trial, has received FDA approval for other uses, indicating a known safety record. Other studies have reported mild to moderate side effects like nausea and tiredness, which were usually not severe.

Overall, the treatments in this trial have demonstrated tolerability, with side effects manageable in a clinical setting. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for digestive system cancers because it combines chemotherapy with a targeted approach using rucaparib. Rucaparib is a PARP inhibitor, which means it helps prevent cancer cells from repairing themselves, making them more susceptible to the effects of chemotherapy. This combination aims to enhance the effectiveness of standard chemotherapy drugs like fluorouracil and irinotecan, potentially leading to better outcomes for patients. Unlike traditional treatments that focus solely on chemotherapy, this approach targets the cancer cells more precisely, potentially reducing the likelihood of disease progression.

What evidence suggests that this trial's treatments could be effective for metastatic digestive system cancers?

Research has shown that using fluorouracil with other chemotherapy drugs can improve response rates in advanced colorectal cancer to 40-50%. Leucovorin enhances the effectiveness of fluorouracil, making it a standard part of treatment for these cancers. Liposomal irinotecan has shown promise, with studies indicating that patients with advanced cancer have a median survival of about 6-10 months. Rucaparib, a PARP inhibitor, demonstrated a 54% response rate in some studies, suggesting it can be effective, especially when tumors cannot repair themselves. In this trial, participants will receive a combination of these treatments, potentially offering more effective options for advanced digestive system cancers by combining their strengths. ^{6 7 8 9 10}

Who Is on the Research Team?

Tanios S Bekaii-Saab

Principal Investigator

Academic and Community Cancer Research United

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6660349/

Impact of 5 Fluorouracil Chemotherapy on Gut Inflammation ... When used in the treatment of CRC, it is estimated that approximately 1% of the injected compound reaches the colon to induce a potential anti-tumor effect.

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK549808/

Fluorouracil - StatPearls - NCBI Bookshelf The overall response rate of advanced colorectal cancer to fluorouracil monotherapy is only 10% to 15% and 40% to 50% when combined with other chemotherapeutic ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2468202023000384

Gut microbiota: Impact on 5-fluorouracil efficacy and toxicity The effectiveness of 5-fluorouracil is influenced by the gut microbiome. Butyrate-producing bacteria could protect the host from 5-fluorouracil-induced ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.59

Analysis of the impact of eliminating bolus 5-fluorouracil in ... Background: 5-Fluorouracil (5-FU) is a component of first-line treatment regimens for metastatic colorectal cancer (mCRC).

5. sciencedirect.com sciencedirect.com/science/article/pii/S0753332221000706

5-Fluorouracil (5-FU) resistance and the new strategy to ... Although there has been an improvement in response rate and disease-free survival in various cancers, 5-FU has shown the highest impact in the treatment of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03337087?term=Immunologic%20Factors%20AND%20PALB2&viewType=Table&rank=8&tab=results

Study Results | Liposomal Irinotecan, Fluorouracil, ... Members are chosen based on the scientific skills and knowledge needed to monitor the particular trial. Also called a data safety and monitoring board, or DSMB.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11871866/

Outcomes of Liposomal Irinotecan With 5‐FU and ... This study investigated the effectiveness and safety of liposomal irinotecan plus 5-fluorouracil (5-FU) and leucovorin (LV) as a second-line ...

8. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03337087/

Clinical Trial: NCT03337087 This phase I/II trial studies the side effects and best dose of liposomal irinotecan and rucaparib when given together with fluorouracil and ...

9. asco.org asco.org/abstracts-presentations/ABSTRACT320565

Efficacy and safety of liposomal irinotecan plus fluorouracil ... We analyzed clinical outcomes of nal-IRI + 5-FU/LV in mPAC patients after progression on conventional irinotecan-containing chemotherapy. Methods: In this ...

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40034960/

Outcomes of Liposomal Irinotecan With 5-FU and ... Liposomal irinotecan plus 5-FU/LV regimen is a feasible second-line treatment option for PDAC patients with borderline performance status, with a safety ...