BRCA1 MutationPhase 1NCT04598321
BrUOG 390: Neoadjuvant Treatment With Talazoparib
A Phase 1 study testing Talazoparib Oral Capsule in people with BRCA1 Mutation and BRCA2 Mutation, run by Brown University at 2 sites in United States.
Trial summary
Ovarian cancer is the most fatal gynecologic cancer; in the US alone an estimated 22,000 women will be diagnosed in 2019, with over 13,000 dying of the disease. Approximately half of epithelial ovarian cancers (EOC) exhibit defective DNA repair through alterations in the homologous recombination (HR) pathway, with 14%… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- BRCA1 Mutation, BRCA2 Mutation, Ovarian Cancer
- What is being tested?
- Talazoparib Oral Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 2 sitesUnited States
- Study dates
- 29 Mar 2021to 6 Dec 2022
- Phase
- Phase 1
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Volunteers must have clinical and radiographic evidence of newly detected FIGO stage II, III or IV epithelial ovarian, primary peritoneal or fallopian tube cancer, deemed by a gynecologic oncologist as not amenable to an R0 resection at presentation.
- Institutional confirmation of Müllerian epithelial adenocarcinoma
- Histologic epithelial cell types: high grade serous carcinoma, high grade endometrioid carcinoma, or a combination of these.
- Documented mutation in BRCA1 or BRCA2 by genetic or commercial somatic testing. Reports will require submission at the time of enrollment.
- Measurable disease as defined by RECIST 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be ≥ 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or ≥ 20 mm when measured by chest x-ray. Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI.14
- Age ≥ 18
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- Adequate hematologic function determined within 28 days of consent as follows:
- ANC greater than or equal to 1,500/mcl. NOTE: ANC cannot have been induced by granulocyte colony stimulating factors.
- Platelets greater than or equal to 100,000/mcl
- Hemoglobin greater than 10 mg/dl (NOTE: While transfusions are permitted to achieve baseline hemoglobin level, patients must not have transfusion within 14 days prior to obtaining baseline screening labs)
- Creatinine Clearance > 15 mL/min. (NOTE: Please see Section 6.2.1 for dosing requirements for patients with renal insufficiency)
- CrCl = (140- age in years) x weight in kg x 0.85/ 72 x serum creatinine in mg/ dL
- Adequate hepatic function within 14 days prior to registration defined as follows:
- Bilirubin ≤ 1.5 x ULN
- ALT and AST < 2.5 x ULN
- Alkaline phosphatase ≤ 2.5 x ULN
- Neurologic function: Neuropathy (sensory and motor) less than or equal to CTCAE v5.0 Grade 1.
- Ability to swallow and retain oral medication. Adequate gastrointestinal absorption with no use of parenteral nutrition within two weeks of trial enrollment and no evidence of bowel obstruction.
- The volunteer must provide study-specific informed consent prior to study entry.
Who cannot join
- Suspected non-gynecologic malignancy, evidenced by tumor markers and/or histologic evaluation.
- Prior history of other invasive malignancies, with the exception of nonmelanoma skin cancer and other specific malignancies as noted in Section 4.2.4 and Section 4.2.5 are excluded if there is any evidence of other malignancy being present within the last three years (2 years for breast cancer, see Section 4.2.4). Volunteers are also excluded if their previous cancer treatment contraindicates this protocol therapy.
- Prior chemotherapy for any abdominal or pelvic tumor within the last three years is excluded. Volunteers may have received prior adjuvant chemotherapy and radiotherapy for localized breast cancer, provided that it was completed more than 2 years prior to registration, the volunteer remains free of recurrent or metastatic disease and hormonal therapy has been discontinued.
- Prior radiotherapy to any portion of the abdominal cavity or pelvis or thoracic cavity within the last three years are excluded. Prior radiation for localized cancer of the head and neck or skin is permitted, provided that it was completed more than three years prior to registration, and the volunteer remains free of recurrent or metastatic disease.
- Synchronous primary endometrial cancer, or a past history of primary endometrial cancer, unless all of the following conditions are met: Stage not greater than I-A, grade 1 or 2, no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including serous, clear cell or other FIGO grade 3 lesions.
- Severe, active co-morbidity defined as follows:
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- Chronic or current active infectious disease requiring systemic antibiotics, antifungal or antiviral treatment
- Known brain or central nervous system metastases or history of uncontrolled seizures
- Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from enrollment, New York Heart Association Class III or IV congestive heart failure, and serious arrhythmia requiring medication (this does not include asymptomatic atrial fibrillation with controlled ventricular rate).
- Partial or complete gastrointestinal obstruction
- Volunteers who are not candidates for major abdominal surgery due to known medical comorbidities.
- Volunteers with any condition that in the judgment of the investigator would jeopardize safety or volunteer compliance with the protocol.
- Concurrent anticancer therapy (e.g. chemotherapy, radiation therapy, biologic therapy, immunotherapy, hormonal therapy, investigational therapy).
- Receipt of an investigational study drug for any indication within 30 days or 5 half-lives (whichever is longer) prior to Day 1 of protocol therapy.
- Prior exposure to a PARP inhibitor.
- People of child-bearing potential (WOCB). This includes:
- Any volunteer who has experienced menarche and who has not undergone surgical sterilization (hysterectomy and/or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12-month amenorrhea in a woman over 45 in the absence of other biological or physiological causes.
- Volunteers who are pregnant or nursing. Volunteers 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 7 months after completing therapy.
- People with an intact uterus and ovaries must have a screening negative serum or urine pregnancy test within 14 days of registration. A second pregnancy test must be done within 24 hours prior to the start of the first cycle of study treatment
- Potent P-gp inhibitors that result in ≥ 2-fold increase in the exposure of an in vivo probe P-gp substrate, including: amiodarone, carvedilol, clarithromycin, cobicistat, dronedarone, erythromycin, glecaprevir/pibrentasvir, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, sofosbuvir/velpatasvir/voxilaprevir, telaprevir, tipranavir, valspodar and verapamil.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Rhode Island Hospital
Providence, Rhode Island, 02903
Women & Infants Hospital
Providence, Rhode Island, 02903
About this study
Official title: BrUOG 390: Neoadjuvant Treatment With Talazoparib for Women With Newly Diagnosed, Advanced Ovarian Cancer Associated With a Mutation in BRCA1 or BRCA2 (mBRCA)
Ovarian cancer is the most fatal gynecologic cancer; in the US alone an estimated 22,000 women will be diagnosed in 2019, with over 13,000 dying of the disease. Approximately half of epithelial ovarian cancers (EOC) exhibit defective DNA repair through alterations in the homologous recombination (HR) pathway, with 14% accounted for by germline mutations in BRCA genes (mBRCA); this goes up to about one in five (20%) women when one includes tumor-associated (somatic) mBRCA.The approach to women with mBRCA-associated ovarian cancer has heralded precision treatment in our field with the availability of PARP inhibitors. Now indicated as treatment for women with documented mBRCA (genomic or somatic), it also has shown significant benefits for women with recurrent EOC who respond to platinum-based therapy when administered as maintenance treatment.
- Conditions
- BRCA1 Mutation, BRCA2 Mutation, Ovarian Cancer, Fallopian Tube Cancer, High Grade Serous Carcinoma
- Being tested
- Talazoparib Oral Capsule
- Medical subject headings
- Ovarian Neoplasms, Fallopian Tube Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Talazoparib Oral CapsuleDrug
Also called Talzenna
An orally available PARP inhibitor for the treatment of advanced breast cancer with germline BRCA mutations.
| Study group | Role | What they receive |
|---|---|---|
| Planned Therapy | Experimental | Talazoparib monotherapy as 1 mg capsule orally on a daily basis for three cycles, defined as a 21-day period, prior to surgery. Volunteers will continue treatment to complete three cycles, unless disease progression or unacceptable toxicity occurs.Volunteers who complete neoadjuvant treatment with talazoparib should undergo surgical cytoreduction within three weeks of their last dose of talazoparib. All volunteers should then undergo standard of care adjuvant therapy using carboplatin and paclitaxel. For volunteers, who agree to continue talazoparib as maintenance therapy, treatment should begin three weeks (+/- 2 weeks) from the end of adjuvant chemotherapy or after cytoreductive surgery alone. Receives: Drug: Talazoparib Oral Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the Preliminary Effectiveness of Talazorparib
Define the proportion of volunteers completing the planned 9 weeks of treatment without disease progression.
Measured: First 9 weeks of treatment
Secondary outcomes (1)
Feasibility of the Trial Design.
Define whether 30 volunteers can successfully be enrolled within 2 years within participating institutions.
Measured: First 2 years of study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2020
- Study start29 Mar 2021
- Primary completion30 Nov 2022
- Study completion6 Dec 2022
Why it stopped: termination of research grant agreement
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 BRCA1 MutationStudies of the same condition, open and under way.
- More trials run by Brown UniversityThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brown University
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, Lifespan
- Responsible party
- Sponsor
- Investigators
- Don S Dizon, MD, Principal investigator, Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04598321
- Sponsor's protocol ID
- BrUOG 390
- Status last verified
- Dec 2022
- First submitted
- 16 Oct 2020
- Last updated
- 12 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BrUOG 390: Neoadjuvant Treatment With Talazoparib for Women With Newly Diagnosed, Advanced Ovarian Cancer Associated With a Mutation in BRCA1 or BRCA2 (mBRCA)
- ClinicalTrials.gov ID
- NCT04598321
- Acronym / sponsor ID
- BrUOG 390
- Conditions
- BRCA1 Mutation, BRCA2 Mutation, Ovarian Cancer, Fallopian Tube Cancer, High Grade Serous Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: termination of research grant agreement
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Brown UniversityUniversity, hospital or other
- Collaborators
- Pfizer, Lifespan
- Study start
- 29 Mar 2021 (actual)
- Primary completion
- 30 Nov 2022 (actual)
- Study completion
- 6 Dec 2022 (actual)
- First posted
- 22 Oct 2020 (actual)
- Results
- Posted 12 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ovarian cancer is the most fatal gynecologic cancer; in the US alone an estimated 22,000 women will be diagnosed in 2019, with over 13,000 dying of the disease. Approximately half of epithelial ovarian cancers (EOC) exhibit defective DNA repair through alterations in the homologous recombination (HR) pathway, with 14% accounted for by germline mutations in BRCA genes (mBRCA); this goes up to about one in five (20%) women when one includes tumor-associated (somatic) mBRCA.The approach to women with mBRCA-associated ovarian cancer has heralded precision treatment in our field with the availability of PARP inhibitors. Now indicated as treatment for women with documented mBRCA (genomic or somatic), it also has shown significant benefits for women with recurrent EOC who respond to platinum-based therapy when administered as maintenance treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Planned Therapy | Experimental | Drug: Talazoparib Oral CapsuleTalazoparib monotherapy as 1 mg capsule orally on a daily basis for three cycles, defined as a 21-day period, prior to surgery. Volunteers will continue treatment to complete three cycles, unless disease progression or unacceptable toxicity occurs.Volunteers who complete neoadjuvant treatment with talazoparib should undergo surgical cytoreduction within three weeks of their last dose of talazoparib. All volunteers should then undergo standard of care adjuvant therapy using carboplatin and paclitaxel. For volunteers, who agree to continue talazoparib as maintenance therapy, treatment should begin three weeks (+/- 2 weeks) from the end of adjuvant chemotherapy or after cytoreductive surgery alone. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Volunteers must have clinical and radiographic evidence of newly detected FIGO stage II, III or IV epithelial ovarian, primary peritoneal or fallopian tube cancer, deemed by a gynecologic oncologist as not amenable to an R0 resection at presentation.
- Institutional confirmation of Müllerian epithelial adenocarcinoma
- Histologic epithelial cell types: high grade serous carcinoma, high grade endometrioid carcinoma, or a combination of these.
- Documented mutation in BRCA1 or BRCA2 by genetic or commercial somatic testing. Reports will require submission at the time of enrollment.
- Measurable disease as defined by RECIST 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be ≥ 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or ≥ 20 mm when measured by chest x-ray. Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI.14
Key exclusion criteria (20 listed)
- Suspected non-gynecologic malignancy, evidenced by tumor markers and/or histologic evaluation.
- Prior history of other invasive malignancies, with the exception of nonmelanoma skin cancer and other specific malignancies as noted in Section 4.2.4 and Section 4.2.5 are excluded if there is any evidence of other malignancy being present within the last three years (2 years for breast cancer, see Section 4.2.4). Volunteers are also excluded if their previous cancer treatment contraindicates this protocol therapy.
- Prior chemotherapy for any abdominal or pelvic tumor within the last three years is excluded. Volunteers may have received prior adjuvant chemotherapy and radiotherapy for localized breast cancer, provided that it was completed more than 2 years prior to registration, the volunteer remains free of recurrent or metastatic disease and hormonal therapy has been discontinued.
- Prior radiotherapy to any portion of the abdominal cavity or pelvis or thoracic cavity within the last three years are excluded. Prior radiation for localized cancer of the head and neck or skin is permitted, provided that it was completed more than three years prior to registration, and the volunteer remains free of recurrent or metastatic disease.
- Synchronous primary endometrial cancer, or a past history of primary endometrial cancer, unless all of the following conditions are met: Stage not greater than I-A, grade 1 or 2, no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including serous, clear cell or other FIGO grade 3 lesions.
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 |
|---|---|---|
| Talazoparib Oral CapsuleAlso: TalzennaAn orally available PARP inhibitor for the treatment of advanced breast cancer with germline BRCA mutations. | Drug | Planned Therapy |
Primary outcome
Determine the Preliminary Effectiveness of Talazorparib
Time frame: First 9 weeks of treatment
Define the proportion of volunteers completing the planned 9 weeks of treatment without disease progression.
1 secondary outcome
Feasibility of the Trial Design.
Time frame: First 2 years of study.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Don S Dizon, MD principal investigator
Brown University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Talazoparib Oral Capsule in people with BRCA1 Mutation and BRCA2 Mutation, run by Brown University at 2 sites 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 19 inclusion and 20 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: stopped early, as of the sponsor's last update on 12 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Yes. Results are posted in the registry (first posted 12 Oct 2023). 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?
Determine the Preliminary Effectiveness of Talazorparib (time frame: First 9 weeks of treatment). 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 12 Oct 2023.