Small Cell Lung CancerPhase 1/2NCT04209595
PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers
A Phase 1/2 study testing PLX038, Rucaparib and Ondansetron in people with Small Cell Lung Cancer and Extra-Pulmonary Small Cell Carcinomas, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Cancer, Extra-Pulmonary Small Cell Carcinomas
- What is being tested?
- PLX038, Rucaparib and Ondansetron
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Apr 2020to 24 Feb 2025
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects with:
- histologically confirmed solid tumors (Phase I), OR
- histologically or cytologically confirmed small cell lung cancer (SCLC) (Phase II), OR
- histologically or cytologically confirmed extra-pulmonary small cell carcinomas (Phase II).
- Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of PLX038 (PEGylated SN38) in combination with rucaparib in participants <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
- Subjects must have progressed on or after standard first-line systemic chemotherapy and have no effective treatment options.
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- Participants must have disease that is not amenable to potentially curative resection.
- Participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- Participants with asymptomatic brain metastases and treated brain metastases are eligible.
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
- Adequate hematological function defined by:
- white blood cell (WBC) count greater than or equal to 3 x 10^9/L,
- absolute neutrophil count (ANC) greater than or equal to 1.5 x10^9/L,
- platelet count greater than or equal to 100 x 10^9/L,
- Hemoglobin (Hgb) greater than or equal to 9 g/ dL
- Adequate hepatic function defined by:
- a total bilirubin level less than or equal to 1.5 x upper limit of normal (ULN),
- an aspartate aminotransferase (AST) level less than or equal to 2.5xULN, (less than or equal to 5X ULN if liver metastasis)
- an alanine transaminase (ALT) level less than or equal to 2.5 xULN, (less than or equal to 5X ULN if liver metastasis).
- Adequate renal function defined by:
- Creatinine OR Measured, or calculated creatinine clearance (CrCl) (estimated glomerular filtration rate (eGFR) may also be used in place of CrCl): < 1.5x institution upper limit of normal OR greater than or equal to 45 mL/min/1.73 m^2 for participant with creatinine levels greater than or equal to 1.5 X institutional ULN.
- Note: Creatinine clearance (CrCl) or eGFR should be calculated per institutional standard.
- The effects of the study treatment on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment and up to 6 months after the last dose of the study drug (s). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Subjects must be able to understand and willing to sign a written informed consent document.
Who cannot join
- Participants who are receiving any other investigational agents.
- Systemic anti-cancer treatment or major surgery within 2 weeks prior to enrollment.
- Radiotherapy within 24 hours prior to enrollment.
- Participants who require treatment with strong inhibitors or inducers of Cytochrome P450, family 3, subfamily A (CYP3A) or with uridine diphosphate glucuronosyltransferase 1A1 gene (UGT1A1) inhibitors during the planned period of investigational treatment with PLX038.
- Participants with known Gilbert's syndrome.
- Participants homozygous for the UGT1A1*28 variant allele with severely reduced UGT1A1 activity.
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- Participants with known human immunodeficiency virus (HIV), hepatitis C virus (HCV), Hepatitis B virus (HBV) status on antiviral drugs are excluded due to the absence of previous experience with concurrent use of antiviral medications and the investigational drug product to be evaluated in the current study and possible for adverse pharmacokinetic and/or pharmacodynamic interactions.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to PLX038 or rucaparib.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that may impair the participants tolerance of study treatments.
- Pregnant women are excluded from this study because PEGSN38 and rucaparib potential for teratogenic or abortifacient effects are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with PEGSN38 and rucaparib, breastfeeding should be discontinued if the mother is treated with study drugs.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Phase I/II Trial of PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers
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.
Read more
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....
Read the detailed description
Background:
- We hypothesize that a dose-escalation strategy that incorporates tumor targeted deoxyribonucleic acid (DNA)-damaging chemotherapy and DNA-damage response (DDR) inhibitors could allow safe and effective administration of DNA damage response (DDR) inhibitor-chemotherapy combination.
- PLX038 is a PEGylated conjugate of SN38 with improved properties including increased solubility, higher exposure and longer half-life. SN-38 is the active metabolite of CPT-11 (irinotecan) that inhibits topoisomerase 1 (Top1) and causes DNA strand breakage. As a specific DNA damaging agent, SN-38 enhances cell kill in tumors deficient in the DNA-damage response and when combined with inhibitors of the DDR.
- Rucaparib is a potent oral poly ADP ribose polymerase (PARP) inhibitor that is approved for the maintenance treatment of participants with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.
- We hypothesize that the combination of PLX038 plus rucaparib is more efficacious than either agent alone.
Objectives:
- Phase I: To identify the maximum tolerated dose (MTD) of PLX038 in combination with rucaparib.
- Phase II: To assess the efficacy with respect to clinical benefit rate (CBR) (CR+PR+SD) for 4 months according to Response Evaluation Criteria (RECIST 1.1) of a combination of PLX038 and rucaparib in participants with small cell lung cancer and extra-pulmonary small cell carcinomas.
Eligibility:
- Subjects with histologically confirmed solid tumors (Phase I) OR histologically or cytologically confirmed small cell lung cancer (SCLC) (Phase II) OR histologically or cytologically confirmed extra-pulmonary small cell carcinomas (Phase II).
- Age greater than or equal to 18 years
- Subjects must have evaluable, or measurable disease.
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
- Adequate organ function
Design:
- This is an open label Phase I/II trial accruing initially one cohort to determine maximum tolerated dose (MTD) of combined treatment of PLX038 and rucaparib (Phase I); and to examine the safety and efficacy of PLX038 in combination with rucaparib in the following cohort (Phase II).
- PLX038 will be administered by intravenous (IV) infusion on day 1 of every 21-days cycle, rucaparib will be administered by mouth (PO) twice daily on days 6 to 19 of every cycle.
- Treatment will continue until progression or unacceptable toxicity.
- Biomarkers of participant response to treatment will be investigated in an exploratory manner pre- and post-treatment.
- Being tested
- PLX038, Rucaparib, Ondansetron
- Keywords
- PARP Inhibitor, Chemotherapy, DDR Inhibitor
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PLX038Drug
Also called PEGylated SN38
Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days).
RucaparibDrug
Also called Rubraca
Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.
OndansetronDrug
Also called Zofran
Participants will be recommended to have 8 mg of ondansetron taken with a small meal or snack to prevent nausea and vomiting approximately 30 minutes prior to each dose of rucaparib.
| Study group | Role | What they receive |
|---|---|---|
| Phase I Arm 1 Level -1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 200 mg | Experimental | 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) Receives: Drug: PLX038; Drug: Rucaparib; Drug: Ondansetron |
| Phase I Arm 1 Level 1, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 400 mg | Experimental | 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) Receives: Drug: PLX038; Drug: Rucaparib; Drug: Ondansetron |
| Phase I - Arm 1 Level 1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 300 mg | Experimental | 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) Receives: Drug: PLX038; Drug: Rucaparib; Drug: Ondansetron |
| Phase IIA Arm 2 | Experimental | 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). Receives: Drug: PLX038; Drug: Rucaparib; Drug: Ondansetron |
| Phase IIB Arm 2 | Experimental | 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). Receives: Drug: PLX038; Drug: Rucaparib; Drug: Ondansetron |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase II: Clinical Benefit Rate
Assess the efficacy with respect to clinical benefit rate (CBR) (Complete Response (CR)+ partial response (PR)+ stable disease (SD) for 4 months according to Response Evaluation Criteria (RECIST 1.1) of a combination of PLX038(PEGylated SN38) and rucaparib in previously treated participants with small cell lung cancer and extra-pulmonary small cell carcinomas. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). CR is disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Measured: Disease progression at 4 months
Phase I: Maximum Tolerated Dose (MTD) of PLX038 (PEGylated SN38) in Combination With Rucaparib
Maximum tolerated dose (MTD) of PLX038 (PEGylated SN38) in combination with rucaparib. The MTD is the dose level at which no more than 1 of 6 participants experience dose limiting toxicity (DLT) during the DLT evaluation period, and the dose below that at which at least 2 (of 6) participants have DLT as a result of the drug. A DLT is (if deemed drug-related) a Grade 4 neutropenia that does not resolve within 7 days; Grade 4 thrombocytopenia or grade 3 thrombocytopenia complicated with hemorrhage; Grade 4 anemia that does not resolve within 7 days despite optimal therapy; Inability to begin subsequent treatment course within 21 days of the scheduled date, due to study drug toxicity.
Measured: One cycle, approximately 21 (+7) days
Secondary outcomes (4)
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib
The safety of the treatment will be monitored, and any toxicities identified will be reported by type and grade. Toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.
Measured: Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.
Phase IIA Progression-free Survival (PFS)
Among participants in the phase IIA cohort, median progression free survival (PFS) will be calculated from the on-study date using the Kaplan-Meier method, along with 95% confidence intervals on the median PFS. PFS is defined as the time from on-study date to documented evidence of disease progression. Disease progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And appearance of one or more new lesions.
Measured: Time from the on-study date to documented evidence of disease progression
Phase IIA Overall Survival
Among participants in the phase IIA cohort, median overall survival (OS) will be calculated from the on-study date using the Kaplan-Meier method, along with 95% confidence intervals on the median OS.OS is defined as the date of on-study to the date of death from any cause or last follow-up.
Measured: Date of on-study to the date of death from any cause or last follow-up
Phase I - Number of Participants Who Experience a Clinical Response (Complete Response (CR)+Partial Response (PR)
The number of participants who experience a clinical response (Complete Response (CR)+Partial Response (PR) will be reported. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). CR is disappearance of all target lesions; any pathological lymph nodes must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Measured: Disease progression, a median of 43 days with range of 20 to 350 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2019
- Study start8 Apr 2020
- Primary completion13 Aug 2021
- Study completion24 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, James Gulley, M.D., National Cancer Institute (NCI)
- Investigators
- James Gulley, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04209595
- Sponsor's protocol ID
- 200013
- Other IDs
- 20-C-0013
- Status last verified
- Aug 2026
- First submitted
- 21 Dec 2019
- Last updated
- 26 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers
- ClinicalTrials.gov ID
- NCT04209595
- Acronym / sponsor ID
- 200013
- Keywords
- PARP Inhibitor, Chemotherapy, DDR Inhibitor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 8 Apr 2020 (actual)
- Primary completion
- 13 Aug 2021 (actual)
- Study completion
- 24 Feb 2025 (actual)
- First posted
- 24 Dec 2019 (actual)
- Results
- Posted 3 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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....
Detailed description
Background:
- We hypothesize that a dose-escalation strategy that incorporates tumor targeted deoxyribonucleic acid (DNA)-damaging chemotherapy and DNA-damage response (DDR) inhibitors could allow safe and effective administration of DNA damage response (DDR) inhibitor-chemotherapy combination.
- PLX038 is a PEGylated conjugate of SN38 with improved properties including increased solubility, higher exposure and longer half-life. SN-38 is the active metabolite of CPT-11 (irinotecan) that inhibits topoisomerase 1 (Top1) and causes DNA strand breakage. As a specific DNA damaging agent, SN-38 enhances cell kill in tumors deficient in the DNA-damage response and when combined with inhibitors of the DDR.
- Rucaparib is a potent oral poly ADP ribose polymerase (PARP) inhibitor that is approved for the maintenance treatment of participants with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.
- We hypothesize that the combination of PLX038 plus rucaparib is more efficacious than either agent alone.
Objectives:
- Phase I: To identify the maximum tolerated dose (MTD) of PLX038 in combination with rucaparib.
- Phase II: To assess the efficacy with respect to clinical benefit rate (CBR) (CR+PR+SD) for 4 months according to Response Evaluation Criteria (RECIST 1.1) of a combination of PLX038 and rucaparib in participants with small cell lung cancer and extra-pulmonary small cell carcinomas.
Eligibility:
- Subjects with histologically confirmed solid tumors (Phase I) OR histologically or cytologically confirmed small cell lung cancer (SCLC) (Phase II) OR histologically or cytologically confirmed extra-pulmonary small cell carcinomas (Phase II).
- Age greater than or equal to 18 years
- Subjects must have evaluable, or measurable disease.
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
- Adequate organ function
Design:
- This is an open label Phase I/II trial accruing initially one cohort to determine maximum tolerated dose (MTD) of combined treatment of PLX038 and rucaparib (Phase I); and to examine the safety and efficacy of PLX038 in combination with rucaparib in the following cohort (Phase II).
- PLX038 will be administered by intravenous (IV) infusion on day 1 of every 21-days cycle, rucaparib will be administered by mouth (PO) twice daily on days 6 to 19 of every cycle.
- Treatment will continue until progression or unacceptable toxicity.
- Biomarkers of participant response to treatment will be investigated in an exploratory manner pre- and post-treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Phase I Arm 1 Level -1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 200 mg | Experimental | Drug: PLX038, Drug: Rucaparib, Drug: OndansetronPhase 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) |
| Phase I Arm 1 Level 1, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 400 mg | Experimental | Drug: PLX038, Drug: Rucaparib, Drug: OndansetronPhase 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) |
| Phase I - Arm 1 Level 1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 300 mg | Experimental | Drug: PLX038, Drug: Rucaparib, Drug: OndansetronPhase 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) |
| Phase IIA Arm 2 | Experimental | Drug: PLX038, Drug: Rucaparib, Drug: OndansetronPhase 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). |
| Phase IIB Arm 2 | Experimental | Drug: PLX038, Drug: Rucaparib, Drug: OndansetronPhase 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Subjects with:
- Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of PLX038 (PEGylated SN38) in combination with rucaparib in participants <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
- Subjects must have progressed on or after standard first-line systemic chemotherapy and have no effective treatment options.
- Participants must have disease that is not amenable to potentially curative resection.
- Participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Key exclusion criteria (10 listed)
- Participants who are receiving any other investigational agents.
- Systemic anti-cancer treatment or major surgery within 2 weeks prior to enrollment.
- Radiotherapy within 24 hours prior to enrollment.
- Participants who require treatment with strong inhibitors or inducers of Cytochrome P450, family 3, subfamily A (CYP3A) or with uridine diphosphate glucuronosyltransferase 1A1 gene (UGT1A1) inhibitors during the planned period of investigational treatment with PLX038.
- Participants with known Gilbert's syndrome.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PLX038Also: PEGylated SN38Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days). | Drug | Phase I - Arm 1 Level 1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 300 mg, Phase I Arm 1 Level -1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 200 mg, Phase I Arm 1 Level 1, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 400 mg, Phase IIA Arm 2, Phase IIB Arm 2 |
| RucaparibAlso: RubracaPhase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle. | Drug | Phase I - Arm 1 Level 1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 300 mg, Phase I Arm 1 Level -1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 200 mg, Phase I Arm 1 Level 1, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 400 mg, Phase IIA Arm 2, Phase IIB Arm 2 |
| OndansetronAlso: ZofranParticipants will be recommended to have 8 mg of ondansetron taken with a small meal or snack to prevent nausea and vomiting approximately 30 minutes prior to each dose of rucaparib. | Drug | Phase I - Arm 1 Level 1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 300 mg, Phase I Arm 1 Level -1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 200 mg, Phase I Arm 1 Level 1, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 400 mg, Phase IIA Arm 2, Phase IIB Arm 2 |
Primary outcome
Phase II: Clinical Benefit Rate
Time frame: Disease progression at 4 months
Assess the efficacy with respect to clinical benefit rate (CBR) (Complete Response (CR)+ partial response (PR)+ stable disease (SD) for 4 months according to Response Evaluation Criteria (RECIST 1.1) of a combination of PLX038(PEGylated SN38) and rucaparib in previously treated participants with small cell lung cancer and extra-pulmonary small cell carcinomas. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). CR is disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Phase I: Maximum Tolerated Dose (MTD) of PLX038 (PEGylated SN38) in Combination With Rucaparib
Time frame: One cycle, approximately 21 (+7) days
Maximum tolerated dose (MTD) of PLX038 (PEGylated SN38) in combination with rucaparib. The MTD is the dose level at which no more than 1 of 6 participants experience dose limiting toxicity (DLT) during the DLT evaluation period, and the dose below that at which at least 2 (of 6) participants have DLT as a result of the drug. A DLT is (if deemed drug-related) a Grade 4 neutropenia that does not resolve within 7 days; Grade 4 thrombocytopenia or grade 3 thrombocytopenia complicated with hemorrhage; Grade 4 anemia that does not resolve within 7 days despite optimal therapy; Inability to begin subsequent treatment course within 21 days of the scheduled date, due to study drug toxicity.
4 secondary outcomes
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib
Time frame: Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.
Phase IIA Progression-free Survival (PFS)
Time frame: Time from the on-study date to documented evidence of disease progression
Phase IIA Overall Survival
Time frame: Date of on-study to the date of death from any cause or last follow-up
Phase I - Number of Participants Who Experience a Clinical Response (Complete Response (CR)+Partial Response (PR)
Time frame: Disease progression, a median of 43 days with range of 20 to 350 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Gulley, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PLX038, Rucaparib and Ondansetron in people with Small Cell Lung Cancer and Extra-Pulmonary Small Cell Carcinomas, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase II: Clinical Benefit Rate (time frame: Disease progression at 4 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2026.