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: Unknown

10 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Drugs known as poly-adenosine diphosphate ribose polymerase (PARP) inhibitors are known to help stop tumor growth in patients with breast, ovarian cancers and many other cancers including prostate and pancreatic cancers. Many research studies done in animals and human cells have shown that these types of drugs can improve how well chemotherapy works. Standard chemotherapy can be too toxic to be combined with PARP inhibitors. In this study, we use a new form of chemotherapy called PLX038 (PEGylated SN38) to see if it can be safely combined with PARP inhibitors to shrink tumors. 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 tumors, small cell lung cancer (SCLC), or small cell cancer outside their lungs. Design: Participants will be screened with: Physical exam Blood tests Records of their diagnosis (or they will have a tumor biopsy). A review of their symptoms and medications. A review of their ability to perform their normal activities. Electrocardiograms, to measure the electrical activity of the heart. Computed tomography (CT) scans of the chest, abdomen, and pelvis. CT scans are a series of X-rays. Participants will get PLX038 by intravenous catheter on Day 1 of each cycle (1 cycle = 21 days). For this, a small plastic tube is put into an arm vein. They will take rucaparib twice daily by mouth on Days 3 to 19 of each cycle. They will keep a medicine diary. Participants may give a hair sample. They may have optional tumor biopsies. Screening tests are repeated throughout the study. About 30 days after treatment ends, participants will have a safety follow-up visit. They will give blood samples, talk about their health, and get a physical exam. Then they will be called or emailed every 6 months....

Research Team

Anish Thomas, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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.

Treatment Details

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.

Participant Groups

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+