Ignite Creation Date:
2025-12-24 @ 2:19 PM
Ignite Modification Date:
2025-12-25 @ 12:56 PM
Study NCT ID:
NCT04209595
Status:
COMPLETED
Last Update Posted:
2025-03-17
First Post:
2019-12-21
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Phase I/II Trial of PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers
Status:
COMPLETED
Status Verified Date:
2025-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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. 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....
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.
* 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 Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 20-C-0013 | None | None | View |