Breast CancerEarly Phase 1NCT03911453
Window of Opportunity Trial, PARP Inhibitor Rucaparib Affect on PD-L1 Expression in Triple Negative Breast Tumors
A Early Phase 1 study testing Rucaparib in people with Breast Cancer, run by University of Arizona at 1 site in United States.
Trial summary
This is a single arm window of opportunity trial conducted in patients with early stage triple negative breast tumors to evaluate if treatment with a Poly(ADP-ribose) polymerase (PARP) inhibitor will increase expression of programmed cell death-1 with ligand (PD-L1) in triple negative breast tumors. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Rucaparib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Apr 2019to 16 Jul 2021
- Phase
- Early 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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have histologically documented triple negative breast cancer (TNBC) (defined as ER expression ≤10% by IHC, progesterone receptor (PR) expression≤10% by IHC and HER2 0 or 1+ by IHC or Fluorescence in situ hybridization (FISH) ratio <2 or human epidermal growth factor receptor 2 (HER2) gene copy number of <6)
- Early stage breast cancer (stage I-III) and not be candidate for neoadjuvant chemotherapy
- Be informed of the investigational nature of the study and all pertinent aspects of the trial
- Have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Have the ability to understand and the willingness to sign a written informed consent document in accordance with institutional and federal guidelines
- Be ≥ 21 years of age
Show all 9Show fewer
- Have serum creatinine < 1.5 x institutional upper limit of normal (IULN) or a calculated creatinine clearance ≥ 30ml/min (calculated by Cockcroft Gault equation), bilirubin ≤ 2.0, and an serum glutamic oxaloacetic transaminase (SGOT)/s erum glutamic pyruvic transaminase (SGPT)/alkaline phosphatase ≤ 2.0 x IULN
- Have adequate bone marrow function (ANC >1000, Platelets >100,000/ml, Hemoglobin >10gm/dL)
- Women of childbearing potential or male patients of reproductive potential with female partners of childbearing potential must not consider getting pregnant and must avoid pregnancy during the study and for at least 6 months after the last dose of rucaparib. Female and male patients of reproductive potential must practice highly effective methods of contraception with their partners, if of reproductive potential, during treatment and for 6 months following last dose of rucaparib
Who cannot join
- Ongoing or prior treatment with a PARPi for breast cancer or other malignancies
- Receiving concurrent anti-neoplastic therapy for their breast cancer or another malignancy
- Known documented or suspected hypersensitivity to the components of the study drug or analogs.
- Pre-existing gastrointestinal disorders or defects (like duodenal stent etc) that would, in the opinion of the investigator, interfere with absorption of rucaparib
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Arizona Cancer Center
Tucson, Arizona, 85724
About this study
Official title: Window of Opportunity Trial to Evaluate Change in PD-L1 Expression in Triple Negative Breast Tumors in Response to the PARP Inhibitor Rucaparib
This is a single arm window of opportunity trial conducted in patients with early stage triple negative breast tumors to evaluate if treatment with a Poly(ADP-ribose) polymerase (PARP) inhibitor will increase expression of programmed cell death-1 with ligand (PD-L1) in triple negative breast tumors.
Read the detailed description
This is a single arm window of opportunity trial conducted in patients with early stage triple negative breast tumors. Patients who are planning to undergo surgery as part of their initial treatment will be eligible for this study. They will be treated with single agent rucaparib for 3 weeks and then proceed to surgery. Core-biopsies obtained at the time of diagnosis and tumor from the surgical resection will be assessed for change in expression of PD-L1 by Immunohistochemical assay (IHC).
- Conditions
- Breast Cancer
- Being tested
- Rucaparib
- Keywords
- Breast Cancer, Triple Negative, Breast Tumors, PD-L1, PARP, PARPi, Rucaparib
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RucaparibDrug
Patients will be treated with single agent rucaparib for 3wks and then proceed to surgery. Core-biopsies (at the time of diagnosis) and tumor from the surgical resection will be assessed for change in expression of PD-L1 by Immunohistochemical assay (IHC).
| Study group | Role | What they receive |
|---|---|---|
| Treatment (rucaparib) | Experimental | Patients will be treated with single agent rucaparib for 3wks and then proceed to surgery. Core-biopsies (at the time of diagnosis) and tumor from the surgical resection will be assessed for change in expression of programmed cell death-1 with ligand (PD-L1) by immunohistochemistry (IHC)
. Starting Dose 600 mg twice daily Dose Level -1 500 mg twice daily Dose Level -2 400 mg twice daily Dose Level -3 300 mg twice daily Receives: Drug: Rucaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of expression of PD-L1 by IHC via core biopsy.
To evaluate change in expression of programmed cell death-1 with ligand (PD-L1) by Immunohistochemistry (IHC) of tissue sample via core biopsy after treatment with single agent PARPi (rucaparib).
Measured: Six months
Secondary outcomes (5)
Measure change in expression of Ki67 by IHC after treatment with PARPi.
Measure change in expression of Ki67 by immunohistochemistry of tissue sample via core biopsy after treatment with single agent Poly(ADP-ribose) polymerase inhibitor (PARPi) (rucaparib).
Measured: Six months
Measure and quantify change in number of tumor-infiltrating lymphocytes.
Measure and quantify change in number of tumor-infiltrating lymphocytes via blood testing.
Measured: Six months
Measure levels of tumor PARylation in pre- and post-PARPi therapy by IHC.
Measure levels of tumor PARylation (the addition of poly-ADP-ribose polymers) in pre- and post-PARPi therapy by immunohistochemistry of tissue sample via core biopsy.
Measured: Six months
Measure change in expression of programmed cell death-1 with ligand (PD-L1) pre- and post-PARPi therapy in circulating tumor cells (CTCs).
Measure change in expression of programmed cell death-1 with ligand (PD-L1) pre- and post-PARPi therapy in circulating tumor cells (CTCs) via blood/plasma collection.
Measured: Six months
Measure cfDNA mutational expression for homologous recombination deficiency (HRD) and correlate with PD-L1 expression at baseline and change overtime.
Measure circulating free DNA (cfDNA) mutational expression for homologous recombination deficiency (HRD) and correlate with PD-L1 expression at baseline and change overtime via blood/plasma collection.
Measured: Six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2019
- Study start19 Apr 2019
- Primary completion16 Jul 2021
- Study completion16 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University of ArizonaThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pavani Chalasani, MD, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03911453
- Sponsor's protocol ID
- 30388
- Other IDs
- 1903397220
- Status last verified
- Oct 2024
- First submitted
- 9 Apr 2019
- Last updated
- 3 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Window of Opportunity Trial to Evaluate Change in PD-L1 Expression in Triple Negative Breast Tumors in Response to the PARP Inhibitor Rucaparib
- ClinicalTrials.gov ID
- NCT03911453
- Acronym / sponsor ID
- 30388
- Conditions
- Breast Cancer
- Keywords
- Breast Cancer, Triple Negative, Breast Tumors, PD-L1, PARP, PARPi, Rucaparib
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Study start
- 19 Apr 2019 (actual)
- Primary completion
- 16 Jul 2021 (actual)
- Study completion
- 16 Jul 2021 (actual)
- First posted
- 11 Apr 2019 (actual)
- 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.
This is a single arm window of opportunity trial conducted in patients with early stage triple negative breast tumors to evaluate if treatment with a Poly(ADP-ribose) polymerase (PARP) inhibitor will increase expression of programmed cell death-1 with ligand (PD-L1) in triple negative breast tumors.
Detailed description
This is a single arm window of opportunity trial conducted in patients with early stage triple negative breast tumors. Patients who are planning to undergo surgery as part of their initial treatment will be eligible for this study. They will be treated with single agent rucaparib for 3 weeks and then proceed to surgery. Core-biopsies obtained at the time of diagnosis and tumor from the surgical resection will be assessed for change in expression of PD-L1 by Immunohistochemical assay (IHC).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (rucaparib) | Experimental | Drug: RucaparibPatients will be treated with single agent rucaparib for 3wks and then proceed to surgery. Core-biopsies (at the time of diagnosis) and tumor from the surgical resection will be assessed for change in expression of programmed cell death-1 with ligand (PD-L1) by immunohistochemistry (IHC) . Starting Dose 600 mg twice daily Dose Level -1 500 mg twice daily Dose Level -2 400 mg twice daily Dose Level -3 300 mg twice daily |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Have histologically documented triple negative breast cancer (TNBC) (defined as ER expression ≤10% by IHC, progesterone receptor (PR) expression≤10% by IHC and HER2 0 or 1+ by IHC or Fluorescence in situ hybridization (FISH) ratio <2 or human epidermal growth factor receptor 2 (HER2) gene copy number of <6)
- Early stage breast cancer (stage I-III) and not be candidate for neoadjuvant chemotherapy
- Be informed of the investigational nature of the study and all pertinent aspects of the trial
- Have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Have the ability to understand and the willingness to sign a written informed consent document in accordance with institutional and federal guidelines
Key exclusion criteria (4 listed)
- Ongoing or prior treatment with a PARPi for breast cancer or other malignancies
- Receiving concurrent anti-neoplastic therapy for their breast cancer or another malignancy
- Known documented or suspected hypersensitivity to the components of the study drug or analogs.
- Pre-existing gastrointestinal disorders or defects (like duodenal stent etc) that would, in the opinion of the investigator, interfere with absorption of rucaparib
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 |
|---|---|---|
| RucaparibPatients will be treated with single agent rucaparib for 3wks and then proceed to surgery. Core-biopsies (at the time of diagnosis) and tumor from the surgical resection will be assessed for change in expression of PD-L1 by Immunohistochemical assay (IHC). | Drug | Treatment (rucaparib) |
Primary outcome
Measurement of expression of PD-L1 by IHC via core biopsy.
Time frame: Six months
To evaluate change in expression of programmed cell death-1 with ligand (PD-L1) by Immunohistochemistry (IHC) of tissue sample via core biopsy after treatment with single agent PARPi (rucaparib).
5 secondary outcomes
Measure change in expression of Ki67 by IHC after treatment with PARPi.
Time frame: Six months
Measure and quantify change in number of tumor-infiltrating lymphocytes.
Time frame: Six months
Measure levels of tumor PARylation in pre- and post-PARPi therapy by IHC.
Time frame: Six months
Measure change in expression of programmed cell death-1 with ligand (PD-L1) pre- and post-PARPi therapy in circulating tumor cells (CTCs).
Time frame: Six months
Measure cfDNA mutational expression for homologous recombination deficiency (HRD) and correlate with PD-L1 expression at baseline and change overtime.
Time frame: Six months
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 3 Oct 2024.
- Individual participant dataSharing planned: No
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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.
Pavani Chalasani, MD principal investigator
University of Arizona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Rucaparib in people with Breast Cancer, run by University of Arizona 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 9 inclusion and 4 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 3 Oct 2024. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Measurement of expression of PD-L1 by IHC via core biopsy. (time frame: Six months). 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 3 Oct 2024.