Ovarian CancerPhase 1NCT01237067
Olaparib in Combination With Carboplatin for Refractory or Recurrent Women s Cancers
A Phase 1 study testing Carboplatin and Olaparib in people with Ovarian Cancer and Breast Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Ovarian Cancer, Breast Cancer, Primary Peritoneal Cancer
- What is being tested?
- Carboplatin and Olaparib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Feb 2011to 12 Dec 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have confirmed at the NCI, histologically or cytologically recurrent/refractory gynecologic cancers such as but not restricted to epithelial ovarian, fallopian, primary peritoneal, uterine papillary serous cancer, cervix cancer, malignant mixed mullerian tumors, or any type of breast cancer that is metastatic or unresectable and for whom curative therapies do not exist.
- All patients must have measurable and/or evaluable disease; biomarker-only disease is not considered measurable or evaluable; eligibility of bone only disease is a PI decision on an individual patient basis.
- Breast cancer patients with locally advanced, unresectable disease must have been previously treated with standard therapy.
- Breast cancer patients with deleterious mutation in DNA repair enzymes with locally advanced or metastatic disease do not have to have had prior therapy for their progressive disease. Men with BRCA1/2 mutation and metastatic breast cancer will be eligible for study. Ovarian or endometrial cancer patients with deleterious mutation in DNA repair enzymes may be treated in first recurrence independent of platinum-sensitivity history.
- There is no limit on number of prior therapies. Patients must be at least 6 months from their last platinum exposure and platinum-resistant patients may participate.
- Age greater than or equal to 18 years
Show all 17Show fewer
- ECOG performance status less than or equal to 2
- Patients must have normal organ and marrow function as defined below:
- Absolute neutrophil count greater than or equal to 1,500/mm3
- Platelets greater than or equal to 100,000/mm3
- Serum Creatinine less or than or equal to 1.5 mg/dL or if low, Cr Cl greater than 60 mL/min
- Total bilirubin less than or equal to 1.5 times the limit of normal (ULN) in the absence of Gilbert s syndrome
- AST(SGOT0/ALT(SGPT) less than or equal to 3 times the ULN (CTCAE4.0 grade 2)
- Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least three months following the last dose of experimental therapy.
- Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to the start of the study.
- Ability to understand and the willingness to sign a written informed consent document
- Inclusion of Women and Minorities: Women and members of all races and ethnic groups are eligible for this trial.
Who cannot join
- Patients who have had treatment for their disease, such as chemotherapy, biological therapy, radiotherapy, surgery, or complementary and alternative therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
- Patients who were treated with other PARP inhibitors greater than 28 days prior to study are eligible.
- Must be at least 2 weeks from the last phase 0 intervention (longer at the discretion of the PI) and at least 1 day from non-cancer-related complementary and alternative medicine prior to entering the study.
- Previous treatment with olaparib (AZD2281).
- Invasive cancer, other than co-existent breast/gynecologic cancers, within the past 2 years. Noninvasive nonmelanoma skin cancers are not exclusions.
- Patients with known brain metastases diagnosed within 1 year will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
Show all 16Show fewer
- Patients with brain metastases diagnosed greater than 1 year prior to study entry may be considered if they received sterilizing therapy to the CNS (resection or radiation) and have been CNS recurrence-free for a full 1-year period
- History of grade 4 allergic reactions to platinums:
- Patients with allergic reaction to platinums (up to and including grade 3 without a reaction protocol, and up to and including grade 2 in the face of aggressive pre-treatment) may be eligible pending review of experience, and PI approval.
- Patients who have not been rechallenged after a severe reaction may be eligible on a case-by-case basis.
- Clinically significant GI bleeding or hemoptysis within 28 days prior to the start of the study
- Inability to swallow pills
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (no antibiotics prior to entering the study within 7 days), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant and breast-feeding women: If a woman becomes pregnant or suspects she is pregnant while participating in this study, she should inform her treating physician immediately.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD2281. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy such as carboplatin. HIV- positive patients who are not on combination antiretroviral therapy but with CD4 counts >500, eligibility is a PI decision on an individual patient basis.
- Major surgery within the past 28 days
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Ovarian Cancer, Breast Cancer, Primary Peritoneal Cancer, Fallopian Tube Cancer, Endometrial Cancer
- Being tested
- Carboplatin, Olaparib
- Keywords
- PARP inhibitor, womens's cancers, relapsed, recurrent, Ovarian, breast, endometrial, cervical, Carboplatin, BRCA 1 and BRCA 2
- Medical subject headings
- Ovarian Neoplasms, Breast Neoplasms, Fallopian Tube Neoplasms, Endometrial Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarboplatinDrug
A phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of 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.
OlaparibDrug
A phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of 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.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Dose esc: A phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of 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 Receives: Drug: Carboplatin; Drug: Olaparib |
| Group 2A | Experimental | Randomized: A phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of 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. Receives: Drug: Carboplatin; Drug: Olaparib |
| Group 2B | Experimental | Randomized: A phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of 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. Receives: Drug: Carboplatin; Drug: Olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the pharmacodynamic effects of the sequence of administration of olaparib and carboplatin and the schedule-associated safety of the combination.
Pharmacodynamic study results and toxicity during Cycle 1 at 24 and 48 hours
Measured: Cycle 1 at 24 and 48 hours
Safety of combination of olaparib and carboplatin
Toxicity at the end of Cycle 2
Measured: End of Cycle 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2010 (estimated)
- Study start7 Feb 2011
- Primary completion16 Nov 2014
- Study completion12 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Ovarian 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jung-Min Lee, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01237067
- Sponsor's protocol ID
- 110022
- Other IDs
- 11-C-0022
- Status last verified
- 12 Dec 2019
- First submitted
- 6 Nov 2010
- Last updated
- 17 Dec 2019
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Alderson T. New targets for cancer chemotherapy--poly(ADP-ribosylation) processing and polyisoprene metabolism. Biol Rev Camb Philos Soc. 1990 Nov;65(4):623-41. doi: 10.1111/j.1469-185x.1990.tb01240.x. No abstract available.
PubMed 2124932Berger NA, Adams JW, Sikorski GW, Petzold SJ, Shearer WT. Synthesis of DNA and poly(adenosine diphosphate ribose) in normal and chronic lymphocytic leukemia lymphocytes. J Clin Invest. 1978 Jul;62(1):111-8. doi: 10.1172/JCI109094.
PubMed 659624Cottet F, Blanche H, Verasdonck P, Le Gall I, Schachter F, Burkle A, Muiras ML. New polymorphisms in the human poly(ADP-ribose) polymerase-1 coding sequence: lack of association with longevity or with increased cellular poly(ADP-ribosyl)ation capacity. J Mol Med (Berl). 2000;78(8):431-40. doi: 10.1007/s001090000132.
PubMed 11097112
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01237067
- Acronym / sponsor ID
- 110022
- Conditions
- Ovarian Cancer, Breast Cancer, Primary Peritoneal Cancer, Fallopian Tube Cancer, Endometrial Cancer
- Keywords
- PARP inhibitor, womens's cancers, relapsed, recurrent, Ovarian, breast, endometrial, cervical, Carboplatin, BRCA 1 and BRCA 2
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 7 Feb 2011
- Primary completion
- 16 Nov 2014 (actual)
- Study completion
- 12 Dec 2019 (actual)
- First posted
- 9 Nov 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Carboplatin, Drug: OlaparibDose esc: A phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of 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 |
| Group 2A | Experimental | Drug: Carboplatin, Drug: OlaparibRandomized: A phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of 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. |
| Group 2B | Experimental | Drug: Carboplatin, Drug: OlaparibRandomized: A phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of 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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients must have confirmed at the NCI, histologically or cytologically recurrent/refractory gynecologic cancers such as but not restricted to epithelial ovarian, fallopian, primary peritoneal, uterine papillary serous cancer, cervix cancer, malignant mixed mullerian tumors, or any type of breast cancer that is metastatic or unresectable and for whom curative therapies do not exist.
- All patients must have measurable and/or evaluable disease; biomarker-only disease is not considered measurable or evaluable; eligibility of bone only disease is a PI decision on an individual patient basis.
- Breast cancer patients with locally advanced, unresectable disease must have been previously treated with standard therapy.
- Breast cancer patients with deleterious mutation in DNA repair enzymes with locally advanced or metastatic disease do not have to have had prior therapy for their progressive disease. Men with BRCA1/2 mutation and metastatic breast cancer will be eligible for study. Ovarian or endometrial cancer patients with deleterious mutation in DNA repair enzymes may be treated in first recurrence independent of platinum-sensitivity history.
- There is no limit on number of prior therapies. Patients must be at least 6 months from their last platinum exposure and platinum-resistant patients may participate.
Key exclusion criteria (16 listed)
- Patients who have had treatment for their disease, such as chemotherapy, biological therapy, radiotherapy, surgery, or complementary and alternative therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
- Patients who were treated with other PARP inhibitors greater than 28 days prior to study are eligible.
- Must be at least 2 weeks from the last phase 0 intervention (longer at the discretion of the PI) and at least 1 day from non-cancer-related complementary and alternative medicine prior to entering the study.
- Previous treatment with olaparib (AZD2281).
- Invasive cancer, other than co-existent breast/gynecologic cancers, within the past 2 years. Noninvasive nonmelanoma skin cancers are not exclusions.
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 |
|---|---|---|
| CarboplatinA phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of 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. | Drug | Group 1, Group 2A, Group 2B |
| OlaparibA phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of 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. | Drug | Group 1, Group 2A, Group 2B |
Primary outcome
Determine the pharmacodynamic effects of the sequence of administration of olaparib and carboplatin and the schedule-associated safety of the combination.
Time frame: Cycle 1 at 24 and 48 hours
Pharmacodynamic study results and toxicity during Cycle 1 at 24 and 48 hours
Safety of combination of olaparib and carboplatin
Time frame: End of Cycle 2
Toxicity at the end of Cycle 2
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 2124932Alderson T. New targets for cancer chemotherapy--poly(ADP-ribosylation) processing and polyisoprene metabolism. Biol Rev Camb Philos Soc. 1990 Nov;65(4):623-41. doi: 10.1111/j.1469-185x.1990.tb01240.x. No abstract available.
- Background: PubMed 659624Berger NA, Adams JW, Sikorski GW, Petzold SJ, Shearer WT. Synthesis of DNA and poly(adenosine diphosphate ribose) in normal and chronic lymphocytic leukemia lymphocytes. J Clin Invest. 1978 Jul;62(1):111-8. doi: 10.1172/JCI109094.
- Background: PubMed 11097112Cottet F, Blanche H, Verasdonck P, Le Gall I, Schachter F, Burkle A, Muiras ML. New polymorphisms in the human poly(ADP-ribose) polymerase-1 coding sequence: lack of association with longevity or with increased cellular poly(ADP-ribosyl)ation capacity. J Mol Med (Berl). 2000;78(8):431-40. doi: 10.1007/s001090000132.
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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.
Jung-Min Lee, 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 study testing Carboplatin and Olaparib in people with Ovarian Cancer and Breast Cancer, 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 17 inclusion and 16 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 17 Dec 2019. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Determine the pharmacodynamic effects of the sequence of administration of olaparib and carboplatin and the schedule-associated safety of the combination. (time frame: Cycle 1 at 24 and 48 hours). 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?
On the ClinicalTrials.gov record for NCT01237067, which also lists 3 linked publications.
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 17 Dec 2019.