Ignite Creation Date:
2025-12-25 @ 12:37 AM
Ignite Modification Date:
2026-02-27 @ 11:19 AM
Study NCT ID:
NCT01237067
Status:
COMPLETED
Last Update Posted:
2019-12-17
First Post:
2010-11-06
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Olaparib in Combination With Carboplatin for Refractory or Recurrent Women s Cancers
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Pharmacokinetic/Pharmacodynamic Study With a Phase I Run-In With a PARP Inhibitor (Olaparib) in Combination With Carboplatin for Refractory or Recurrent Women's Cancers
Status:
COMPLETED
Status Verified Date:
2019-12-12
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:
\- Olaparib is an experimental anti-cancer drug that is part of a class of drugs called PARP inhibitors. PARP is a protein that is involved in repairing DNA damage, but it may also encourage precancerous cells to develop into cancer cells. Olaparib has been given safely in combination with carboplatin, a drug used to treat breast, ovarian, uterine, and cervical cancer, but more research is needed to determine whether the drugs are more effective when given together or which drug should be given first.
Objectives:
\- To determine the safety and effectiveness of combined carboplatin and olaparib as a treatment for gynecologic (female organ) or breast cancer.
Eligibility:
* Women at least 18 years of age who have breast, ovarian, uterine, or cervical cancer that has not responded to standard treatments.
* Men at least 18 years of age who have metastatic breast cancer and have a BRCA-1/2 mutation.
Design:
* Participants will be screened with a physical examination and medical history, as well as blood and tumor samples and imaging studies as required by the researchers. Study participants will then be divided into two groups.
* Group 1: Participants will receive olaparib tablets twice a day for 7 days (14 doses) and will receive carboplatin by vein on day 1 or 2, for a 21-day treatment cycle. Group 1 study is designed to determine the safety of new tablet formulation of olaparib.
* Group 2: Participants will be divided into two smaller groups, with reversed treatment schedules. Group 2 study is designed to evaluate which drug should be given first through endpoint studies in blood samples.
* Group 2A: Participants will receive olaparib tablets twice a day for 7 days (14 doses) and then carboplatin on day 8 of the first cycle. Cycle 2 will start with carboplatin on day 1 and olaparib starting on day 2 for 7 days (14 doses).
* Group 2B: Participants will receive carboplatin on the first day of the first cycle, and then olaparib on day 2, twice a day for 7 days (14 doses) of the first cycle. Cycle 2 will start with 7 days of olaparib (14 doses) and carboplatin will be given on day 8.
* From cycle 3 until completion of therapy, all Group 2 participants will follow the schedule used for Group 1 (carboplatin on day 1 or 2 of the week of olaparib therapy, also in 21-day cycles).
* Additional blood and tissue samples and imaging studies will be conducted throughout the treatment period.
* All participants may receive no more than 8 cycles of olaparib and carboplatin therapy, but may continue to take olaparib if their cancer responds to the treatment.
\- Olaparib is an experimental anti-cancer drug that is part of a class of drugs called PARP inhibitors. PARP is a protein that is involved in repairing DNA damage, but it may also encourage precancerous cells to develop into cancer cells. Olaparib has been given safely in combination with carboplatin, a drug used to treat breast, ovarian, uterine, and cervical cancer, but more research is needed to determine whether the drugs are more effective when given together or which drug should be given first.
Objectives:
\- To determine the safety and effectiveness of combined carboplatin and olaparib as a treatment for gynecologic (female organ) or breast cancer.
Eligibility:
* Women at least 18 years of age who have breast, ovarian, uterine, or cervical cancer that has not responded to standard treatments.
* Men at least 18 years of age who have metastatic breast cancer and have a BRCA-1/2 mutation.
Design:
* Participants will be screened with a physical examination and medical history, as well as blood and tumor samples and imaging studies as required by the researchers. Study participants will then be divided into two groups.
* Group 1: Participants will receive olaparib tablets twice a day for 7 days (14 doses) and will receive carboplatin by vein on day 1 or 2, for a 21-day treatment cycle. Group 1 study is designed to determine the safety of new tablet formulation of olaparib.
* Group 2: Participants will be divided into two smaller groups, with reversed treatment schedules. Group 2 study is designed to evaluate which drug should be given first through endpoint studies in blood samples.
* Group 2A: Participants will receive olaparib tablets twice a day for 7 days (14 doses) and then carboplatin on day 8 of the first cycle. Cycle 2 will start with carboplatin on day 1 and olaparib starting on day 2 for 7 days (14 doses).
* Group 2B: Participants will receive carboplatin on the first day of the first cycle, and then olaparib on day 2, twice a day for 7 days (14 doses) of the first cycle. Cycle 2 will start with 7 days of olaparib (14 doses) and carboplatin will be given on day 8.
* From cycle 3 until completion of therapy, all Group 2 participants will follow the schedule used for Group 1 (carboplatin on day 1 or 2 of the week of olaparib therapy, also in 21-day cycles).
* Additional blood and tissue samples and imaging studies will be conducted throughout the treatment period.
* All participants may receive no more than 8 cycles of olaparib and carboplatin therapy, but may continue to take olaparib if their cancer responds to the treatment.
Detailed Description:
Background:
* Olaparib (AZD2281) is an oral PARP-1/2 inhibitor (PARPi) that affects tumors by impairing repair of single stranded DNA and causing double strand breaks. Carboplatin covalently crosslinks DNA causing stalled replication forks repaired through nucleotide excision repair and homologous recombination (HR).
* There is no published data on sequence-specificity of PARPi with platinums. Our preclinical data indicate sequence may be important in growth inhibition and DNA damage and repair.
* We have demonstrated activity and safety with concomitant administration of olaparib and carboplatin.
* We hypothesize that elucidation of sequence specificity may improve upon that clinical benefit by optimizing drug administration and potentially safety.
Objectives:
* To determine safe dose of olaparib tablet with carboplatin.
* To estimate the pharmacokinetic (PK) and pharmacodynamic (PD) effects of two schedules of olaparib and carboplatin using peripheral blood mononuclear cells (PBMCs).
* To determine the schedule-associated safety of olaparib and carboplatin in women s cancers.
Eligibility:
* Adult women with recurrent/refractory epithelial ovarian cancer, fallopian, primary peritoneal, uterine papillary serous cancer, or malignant mixed mullerian tumors, or recurrent/refractory breast cancer that is metastatic or unresectable and for which standard therapies do not exist or are no longer effective. BRCA1/2 mutation carriers will be eligible with any metastatic disease.
* Patients must be off prior chemotherapy, radiation therapy, hormonal therapy, or biological therapy for at least 4 weeks.
* ECOG performance status 0-2 and adequate organ and marrow function.
Design:
* A phase I 3 plus 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the trial will be AUC4.
* Subsequent accrual will randomize patients to one of 2 schedules on cycle 1 with the other schedule on cycle 2. A: olaparib d1-7 \> carbo d8; B: carbo d1 \> olaparib d2-8.
* Cycle 3-8 will be schedule B. After 8 cycles of carboplatin, olaparib will be administered alone on a daily basis.
* Research samples will be obtained for PD endpoints prior to and approximately 24 hours after carboplatin infusion and prior to the 1st and 3rd of olaparib.
* Blood samples for olaparib PK will be obtained in all patients after the first dose of olaparib in cycles 1 and 2.
* Patients will be evaluated for toxicity in clinic every 3 weeks and every two cycles for response using RECIST criteria. Imaging studies will be obtained every 3 cycles for patients who stay on the study longer than four years.
* Olaparib (AZD2281) is an oral PARP-1/2 inhibitor (PARPi) that affects tumors by impairing repair of single stranded DNA and causing double strand breaks. Carboplatin covalently crosslinks DNA causing stalled replication forks repaired through nucleotide excision repair and homologous recombination (HR).
* There is no published data on sequence-specificity of PARPi with platinums. Our preclinical data indicate sequence may be important in growth inhibition and DNA damage and repair.
* We have demonstrated activity and safety with concomitant administration of olaparib and carboplatin.
* We hypothesize that elucidation of sequence specificity may improve upon that clinical benefit by optimizing drug administration and potentially safety.
Objectives:
* To determine safe dose of olaparib tablet with carboplatin.
* To estimate the pharmacokinetic (PK) and pharmacodynamic (PD) effects of two schedules of olaparib and carboplatin using peripheral blood mononuclear cells (PBMCs).
* To determine the schedule-associated safety of olaparib and carboplatin in women s cancers.
Eligibility:
* Adult women with recurrent/refractory epithelial ovarian cancer, fallopian, primary peritoneal, uterine papillary serous cancer, or malignant mixed mullerian tumors, or recurrent/refractory breast cancer that is metastatic or unresectable and for which standard therapies do not exist or are no longer effective. BRCA1/2 mutation carriers will be eligible with any metastatic disease.
* Patients must be off prior chemotherapy, radiation therapy, hormonal therapy, or biological therapy for at least 4 weeks.
* ECOG performance status 0-2 and adequate organ and marrow function.
Design:
* A phase I 3 plus 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the trial will be AUC4.
* Subsequent accrual will randomize patients to one of 2 schedules on cycle 1 with the other schedule on cycle 2. A: olaparib d1-7 \> carbo d8; B: carbo d1 \> olaparib d2-8.
* Cycle 3-8 will be schedule B. After 8 cycles of carboplatin, olaparib will be administered alone on a daily basis.
* Research samples will be obtained for PD endpoints prior to and approximately 24 hours after carboplatin infusion and prior to the 1st and 3rd of olaparib.
* Blood samples for olaparib PK will be obtained in all patients after the first dose of olaparib in cycles 1 and 2.
* Patients will be evaluated for toxicity in clinic every 3 weeks and every two cycles for response using RECIST criteria. Imaging studies will be obtained every 3 cycles for patients who stay on the study longer than four years.
Study Oversight
Has Oversight DMC:
None
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 |
|---|---|---|---|---|
| 11-C-0022 | None | None | View |