Liposomal Irinotecan + Veliparib for Cancer

No longer recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Antiretrovirals, CYP3A4 inhibitors

Disqualifiers: Brain metastases, Lung disease, GI disorders, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two drugs: liposomal irinotecan (a chemotherapy drug) and veliparib (a PARP inhibitor). The aim is to evaluate their effectiveness and side effects in treating solid tumor cancers. Researchers seek to determine the optimal dose that halts tumor growth by blocking the enzymes cancer cells need to grow. This trial may suit individuals with confirmed solid tumor cancer who have no other standard treatments available to improve life expectancy. Participants should not have undergone recent chemotherapy or radiotherapy and must not be pregnant. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment combination.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you need to use medications that strongly affect the liver enzyme CYP3A4. It's best to discuss your current medications with the trial team to see if they might interfere.

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

Research has shown that liposomal irinotecan is often used to treat various cancers and is generally well tolerated. However, about one in four patients in past studies lowered their dose due to side effects. This indicates that some individuals might experience discomfort or reactions requiring dose adjustments.

For veliparib, studies have found it is usually well tolerated, especially in patients with advanced solid tumors. Reported side effects include anemia (a deficiency of healthy red blood cells), low platelet count, nausea, and tiredness.

Overall, both treatments have been used in other studies and have some side effects, but these are often manageable. Participants should consider these potential side effects and consult their healthcare provider before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about liposomal irinotecan combined with veliparib because this duo offers a fresh approach to cancer treatment. Unlike traditional chemotherapies, which broadly target fast-growing cells, liposomal irinotecan delivers its cancer-fighting agent directly to the tumor site using a liposomal delivery system, potentially reducing side effects. Veliparib adds another layer of innovation by inhibiting a protein called PARP, which cancer cells rely on to repair themselves. Together, these treatments aim to enhance effectiveness and limit the harsh impacts often associated with cancer therapies.

What evidence suggests that liposomal irinotecan and veliparib might be effective treatments for solid tumors?

Research has shown that liposomal irinotecan, when combined with other treatments, can fight cancer by remaining in the body longer and targeting tumors more effectively. In some studies, it increased survival by about two months compared to other treatments. Veliparib, administered alongside liposomal irinotecan in this trial, has shown promise in enhancing the effects of chemotherapy, leading to better response rates in some patients. However, it may cause side effects such as nausea and tiredness. Both treatments block enzymes that aid cancer cell growth, making them potentially effective options for treating solid tumors. ^{2 4 5 6 7}

Who Is on the Research Team?

Susan E Bates

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

Adults with solid tumor cancers lacking life-extending standard therapies can join this trial. Prior PARP inhibitor therapy is okay, except for ovarian cancer patients with a BRCA mutation who must have had olaparib. Participants need normal bilirubin levels, acceptable blood counts, and organ function; they should not be pregnant or breastfeeding and must agree to use contraception. Excluded are those with recent chemo/radiotherapy, severe allergies to similar drugs, HIV on antiretrovirals, symptomatic brain metastases, interstitial lung disease, GI disorders preventing pill swallowing.

Inclusion Criteria

Hemoglobin >= 10 g/dL (within 28 days prior to administration of ABT-888)

Leukocytes >= 3,000/mcL (within 28 days prior to administration of ABT-888)

Platelets >= 100,000/mcL (within 28 days prior to administration of ABT-888)

Exclusion Criteria

I have no major GI issues, except for a past treated bowel blockage.

I have been diagnosed with interstitial lung disease.

I have no allergies to veliparib, MM-398, or similar drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive liposomal irinotecan IV over 90 minutes on days 1 and 15 and veliparib PO BID on days 5-12 and 19-25 or 3-12 and 17-25. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Liposomal Irinotecan
• Veliparib

Trial Overview The trial tests the combination of liposomal irinotecan and veliparib for treating solid tumors by blocking enzymes that promote cell growth. It aims to determine the safest doses while monitoring side effects using MRI scans and biomarker analysis in participants without standard treatment options.

How Is the Trial Designed?

Group I: Treatment (liposomal irinotecan, veliparib) Experimental Treatment 5 Interventions

Patients receive liposomal irinotecan IV over 90 minutes on days 1 and 15 and veliparib PO BID on days 5-12 and 19-25 or 3-12 and 17-25. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Within 2-6 days prior to beginning liposomal irinotecan treatment, patients may optionally receive FMX IV and undergo MRI at baseline and 24 hours after FMX infusion.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

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

Outcomes of Liposomal Irinotecan With 5-FU and ... Tumor response rates to liposomal irinotecan + 5-FU/LV were partial response in 3%, stable disease in 23%, and progressive disease in 74%, with ...

2. tandfonline.com tandfonline.com/doi/full/10.2217/fon-2020-0902

Real-World Outcomes Associated with Liposomal ... The authors examined 320 patients treated with liposomal irinotecan-based regimens. About a quarter of the patients had their dose reduced. The data suggest ...

3. onivyde.com onivyde.com/en-us/hcp/clinical-evidence/primary-efficacy-analysis

clinically significant os and pfs ONIVYDE + 5-FU/LV increased median overall survival (OS) by approximately 2 months vs 5-FU/LV alone (primary endpoint)

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e16260

Survival outcomes of liposomal irinotecan in patients with ... The median progression-free survival (mPFS) was 1.9 (95% confidence interval [CI] 1.7 – 2.0) months, while the 6-month PFS rate was 24.4%. The ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12433562/

Effectiveness and cost analysis of liposomal irinotecan in ... The liposomal encapsulation of irinotecan enables prolonged systemic circulation and enhances antitumor efficacy while modulating toxicity ...

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

Outcomes of Liposomal Irinotecan With 5‐FU and ... Tumor response rates to liposomal irinotecan + 5-FU/LV were partial response in 3%, stable disease in 23%, and progressive disease in 74%, with ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S104084282400129X

Safety and efficacy of liposomal irinotecan as the second- ... Liposomal irinotecan showed significantly better overall survival (pooled mean difference=0.29 months (95 % CI=0.18–0.39).