Brief Title
BrUOG 390: Neoadjuvant Treatment With Talazoparib
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)
Brief 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% 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 Phase
Phase 1
Study Type
Interventional
Primary Outcome
Determine the preliminary effectiveness of Talazorparib
Secondary Outcome
Feasibility of the trial design.
Condition
BRCA1 Mutation
Intervention
Talazoparib Oral Capsule
Study Arms / Comparison Groups
Planned Therapy
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
1
Start Date
March 29, 2021
Completion Date
January 2027
Primary Completion Date
September 2023
Eligibility Criteria
Inclusion Criteria:
1. 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.
2. Institutional confirmation of Müllerian epithelial adenocarcinoma
3. Histologic epithelial cell types: high grade serous carcinoma, high grade endometrioid
carcinoma, or a combination of these.
4. Documented mutation in BRCA1 or BRCA2 by genetic or commercial somatic testing.
Reports will require submission at the time of enrollment.
5. 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
6. Age ≥ 18
7. 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)
8. 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
9. 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
10. Neurologic function: Neuropathy (sensory and motor) less than or equal to CTCAE v5.0
Grade 1.
11. 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.
12. The volunteer must provide study-specific informed consent prior to study entry.
Exclusion Criteria:
1. Suspected non-gynecologic malignancy, evidenced by tumor markers and/or histologic
evaluation.
2. 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.
3. 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.
4. 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.
5. 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.
6. Severe, active co-morbidity defined as follows:
- 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
7. Volunteers who are not candidates for major abdominal surgery due to known medical
comorbidities.
8. Volunteers with any condition that in the judgment of the investigator would
jeopardize safety or volunteer compliance with the protocol.
9. Concurrent anticancer therapy (e.g. chemotherapy, radiation therapy, biologic therapy,
immunotherapy, hormonal therapy, investigational therapy).
10. 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.
11. Prior exposure to a PARP inhibitor.
12. 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
13. 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.
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Don S Dizon, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04598321
Organization ID
BrUOG 390
Responsible Party
Sponsor
Study Sponsor
Brown University
Collaborators
Pfizer
Study Sponsor
Don S Dizon, MD, Principal Investigator, Brown University
Verification Date
November 2022