PLX038 + Rucaparib for Solid Cancers and Small Cell Lung Cancer

Overseen By Danielle F Pinkiert, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A inhibitors, UGT1A1 inhibitors

Disqualifiers: HIV, HCV, HBV, Gilbert's syndrome, others

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

Compensation: Varies

Number of Visits: 2

Duration: Until progression or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments to determine if it can safely shrink tumors. The study focuses on using PLX038, a newer chemotherapy, with rucaparib, a drug that helps stop tumor growth, specifically targeting solid tumors and small cell lung cancer. Researchers aim to find out if this combination is both safe and effective. Individuals with solid tumors, small cell lung cancer, or small cell cancer outside the lungs, who have tried other treatments without success, may qualify for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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 take certain drugs that affect liver enzymes (CYP3A or UGT1A1 inhibitors) during the study. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research has shown that rucaparib, a PARP inhibitor, is generally well-tolerated by patients with advanced solid tumors. Studies have found that most patients do not experience severe side effects, though common ones like tiredness and nausea have been reported, usually as mild to moderate.

Specific safety information for PLX038 in humans is limited, as this is an early study. Researchers are closely monitoring patient responses to ensure safety during this initial phase.

The combination of PLX038 and rucaparib is being tested to determine a safe dose for patients. Early trials aim to identify side effects and adjust doses to minimize them. The primary goal is to find a safe combination that effectively shrinks tumors without causing significant issues for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PLX038 combined with Rucaparib because this duo offers a novel approach to treating solid tumors and small cell lung cancer. Unlike the standard chemotherapy options that attack rapidly dividing cells, PLX038 is a PEGylated form of SN38, which allows for more prolonged circulation and targeted delivery, potentially improving effectiveness and reducing side effects. Rucaparib, on the other hand, is a PARP inhibitor that specifically targets cancer cells with DNA repair deficiencies, enhancing the treatment's precision. This combination aims to provide a more effective and personalized treatment strategy, targeting cancer cells more directly and potentially improving patient outcomes.

What evidence suggests that this trial's treatments could be effective for solid tumors and small cell lung cancer?

Studies have shown that PARP inhibitors like rucaparib can stop tumor growth in several cancers, including breast, ovarian, prostate, and pancreatic cancers. Rucaparib effectively maintains treatment for some recurring cancers. This trial will explore combining PLX038, a long-lasting form of chemotherapy, with rucaparib. Lab tests have shown promising results for this combination, especially for tumors lacking certain genes like BRCA1 and ATM. Research suggests that using these treatments together can enhance chemotherapy's effectiveness and might reduce its side effects. Early findings indicate that this combination could shrink tumors in solid cancers and small cell lung cancer (SCLC). ^{1 3 4 6 7}

Who Is on the Research Team?

Anish Thomas, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults with solid tumors or small cell cancers, including lung and extra-pulmonary, who've progressed after standard chemotherapy. They must be able to perform daily activities to a certain extent, have adequate organ function, agree to use contraception during the study and for 6 months after, and sign informed consent. Excluded are those with severe genetic enzyme deficiencies, active viral infections on antivirals, recent radiotherapy or other treatments, breastfeeding women, and those with uncontrolled illnesses.

Inclusion Criteria

Subjects must be able to understand and willing to sign a written informed consent document

I have a confirmed diagnosis of a solid tumor, small cell lung cancer, or small cell cancer outside the lungs.

I can take care of myself and perform daily activities.

Exclusion Criteria

I have been diagnosed with Gilbert's syndrome.

I do not have any severe illnesses or social situations that could affect my treatment.

I haven't had cancer treatment or major surgery in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple visits for physical exams, blood tests, and imaging

Treatment

Participants receive PLX038 by IV on Day 1 and rucaparib orally from Days 3 to 19 in 21-day cycles

Until progression or unacceptable toxicity

IV administration on Day 1 of each cycle, regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 30 days after treatment ends

1 in-person visit, followed by calls or emails every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• PLX038
• Rucaparib

Trial Overview The trial is testing PLX038 (a new form of chemo) combined with rucaparib (a PARP inhibitor) in shrinking tumors. Participants will receive PLX038 intravenously on day one of each cycle (21 days), followed by oral rucaparib from day three to nineteen. The goal is finding a safe dosage that effectively reduces tumor size.

How Is the Trial Designed?

Group I: Phase IIB Arm 2 Experimental Treatment 3 Interventions

Phase IIB Participants with extra-pulmonary small cell carcinomas enrolled at the maximum tolerated dose (MTD) of PLX038 (PEGylated SN38) and rucaparib after the MTD of PLX038 and rucaparib is established. Level 2, PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 600 mg by mouth (PO); Level 3, PLX038, every 3 weeks, 1.7 g/m\^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 600 mg by mouth (PO); Level 4, PLX038, every 3 weeks, 2.3 g/m\^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 600 mg by mouth (PO); Level 2A PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 400 mg by mouth (PO); and/or Level 3A. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 600 mg by mouth (PO).

Group II: Phase IIA Arm 2 Experimental Treatment 3 Interventions

Phase IIA Participants with small cell lung cancer (SCLC) enrolled at the maximum tolerated dose (MTD) of PLX038 (PEGylated SN38) and rucaparib after the MTD of PLX038 and rucaparib is established. Level 2, PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 600 mg by mouth (PO); Level 3, PLX038, every 3 weeks, 1.7 g/m\^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 600 mg by mouth (PO); Level 4, PLX038, every 3 weeks, 2.3 g/m\^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 600 mg by mouth (PO); Level 2A PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 400 mg by mouth (PO); and/or Level 3A. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 600 mg by mouth (PO).

Group III: Phase I Arm 1 Level 1, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 400 mg Experimental Treatment 3 Interventions

Phase I - Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 400 mg by mouth (PO)

Group IV: Phase I Arm 1 Level -1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 200 mg Experimental Treatment 3 Interventions

Phase I - Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 200 mg by mouth (PO)

Group V: Phase I - Arm 1 Level 1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 300 mg Experimental Treatment 3 Interventions

Phase I Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 300 mg by mouth (PO)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04209595

PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors ... To find a safe combination of PLX038 and rucaparib, and to see if this mix will cause tumors to shrink. Eligibility: People age 18 and older with solid tumors, ...

2. ctv.veeva.com ctv.veeva.com/study/plx038-pegylated-sn38-and-rucaparib-in-solid-tumors-and-small-cell-cancers

PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors ... Background: Drugs known as poly-adenosine diphosphate ribose polymerase (PARP) inhibitors are known to help stop tumor growth in patients ...

3. nature.com nature.com/articles/s41598-024-64186-2

PLX038A, a long-acting SN-38, penetrates the blood-tumor ... Central nervous system tumors have resisted effective chemotherapy because most therapeutics do not penetrate the blood-tumor-brain-barrier.

4. withpower.com withpower.com/trial/phase-2-carcinoma-small-cell-3-2020-f84b4

PLX038 + Rucaparib for Solid Cancers and Small Cell ... Objective:To find a safe combination of PLX038 and rucaparib, and to see if this mix will cause tumors to shrink.Eligibility:People age 18 and older with solid ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10673686/

PLX038: A Long-Acting Topoisomerase I Inhibitor With Robust ... PLX038 monotherapy and combination with PARP inhibition potently inhibited the growth of both BRCA1- and ATM-deficient tumors.

6. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/ProtocolDetails.aspx?id=2020-C-0013

NIH Clinical Center: Search the Studies To find a safe combination of PLX038 and rucaparib, and to see if this mix will cause tumors to shrink. Eligibility: People age 18 and older with solid tumors, ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04209595/

Clinical Trial: NCT04209595 Objective: To find a safe combination of PLX038 and rucaparib, and to see if this mix will cause tumors to shrink. Eligibility: People age 18 ...