Olaparib in Treating Patients With Newly Diagnosed BRCA-Mutant Ovarian, Primary Peritoneal, or Fallopian Cancer Before Surgery
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|ClinicalTrials.gov Identifier: NCT03943173|
Recruitment Status : Recruiting
First Posted : May 9, 2019
Last Update Posted : June 1, 2022
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|Condition or disease||Intervention/treatment||Phase|
|BRCA-Mutated Ovarian Carcinoma BRCA1 Gene Mutation BRCA2 Gene Mutation High Grade Fallopian Tube Serous Adenocarcinoma High Grade Ovarian Serous Adenocarcinoma Primary Peritoneal High Grade Serous Adenocarcinoma Stage III Fallopian Tube Cancer AJCC v8 Stage III Ovarian Cancer AJCC v8 Stage III Primary Peritoneal Cancer AJCC v8 Stage IIIA Fallopian Tube Cancer AJCC v8 Stage IIIA Ovarian Cancer AJCC v8 Stage IIIA Primary Peritoneal Cancer AJCC v8 Stage IIIA1 Fallopian Tube Cancer AJCC v8 Stage IIIA1 Ovarian Cancer AJCC v8 Stage IIIA2 Fallopian Tube Cancer AJCC v8 Stage IIIA2 Ovarian Cancer AJCC v8 Stage IIIB Fallopian Tube Cancer AJCC v8 Stage IIIB Ovarian Cancer AJCC v8 Stage IIIB Primary Peritoneal Cancer AJCC v8 Stage IIIC Fallopian Tube Cancer AJCC v8 Stage IIIC Ovarian Cancer AJCC v8 Stage IIIC Primary Peritoneal Cancer AJCC v8 Stage IV Fallopian Tube Cancer AJCC v8 Stage IV Ovarian Cancer AJCC v8 Stage IV Primary Peritoneal Cancer AJCC v8 Stage IVA Fallopian Tube Cancer AJCC v8 Stage IVA Ovarian Cancer AJCC v8 Stage IVA Primary Peritoneal Cancer AJCC v8 Stage IVB Fallopian Tube Cancer AJCC v8 Stage IVB Ovarian Cancer AJCC v8 Stage IVB Primary Peritoneal Cancer AJCC v8||Drug: Chemotherapy Drug: Olaparib Procedure: Therapeutic Conventional Surgery||Early Phase 1|
I. To determine the feasibility of daily olaparib given in the neoadjuvant setting in women with primary advanced high grade non-mucinous epithelial ovarian, fallopian tube, or primary peritoneal cancer.
I. Estimate efficacy of olaparib given in the neoadjuvant setting using response rate (by Response Evaluation Criteria in Solid Tumors [RECIST] in subjects with measurable disease).
II. Estimate proportion of subjects able to proceed immediately to interval tumor reductive surgery (without chemotherapy).
III. Determine progression-free survival (PFS). IV. Determine complete pathologic response rate at the time of surgery. V. Determine the toxicity of daily olaparib given in the neoadjuvant setting. VI. Evaluate the toxicity of chemotherapy given after neoadjuvant olaparib. VII. Measure longitudinal symptom burden of study subjects treated with neoadjuvant olaparib and chemotherapy after olaparib.
I. Explore deoxyribonucleic acid (DNA) copy number and level of ribonucleic acid (RNA) and protein expression in homologous recombination-related pathways before and after treatment with olaparib in women with primary advanced high grade non-mucinous epithelial ovarian, fallopian tube, or primary peritoneal cancer.
II. Correlate molecular results to clinical endpoints including response and survival.
Patients receive olaparib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. After treatment, patients either undergo surgery then receive standard chemotherapy for up to 4 cycles or receive standard chemotherapy within 14 days for up to 4 cycles then undergo surgery in the absence of disease progression or unacceptable toxicity at the discretion of the treating physician.
After completion of study treatment, patients are followed up at 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||17 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||NOW: Neoadjuvant Olaparib Window Trial in Newly Diagnosed BRCA-Mutant Ovarian Cancer|
|Actual Study Start Date :||June 7, 2019|
|Estimated Primary Completion Date :||December 31, 2022|
|Estimated Study Completion Date :||December 31, 2022|
Experimental: Treatment (olaparib)
Patients receive olaparib PO BID on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. After treatment, patients either undergo surgery then receive standard chemotherapy for up to 4 cycles or receive standard chemotherapy within 14 days for up to 4 cycles then undergo surgery in the absence of disease progression or unacceptable toxicity at the discretion of the treating physician.
Given standard chemotherapy
Procedure: Therapeutic Conventional Surgery
- Feasibility of olaparib [ Time Frame: Up to 1 year ]Feasibility defined by number of subjects who are able to receive two cycles of PARP inhibition without unacceptable toxicity or disease progression (new disease or increase of CA125 from baseline > 50%). Will be analyzed using descriptive statistics. Will be estimated using a 90% credible interval
- Response rate [ Time Frame: U to 1 year ]For categorical endpoints, standard descriptive statistics, including frequency table and exact 95% confidence intervals will be computed using the Clopper-Pearson method.
- Complete pathologic response [ Time Frame: For up to 1 year ]For categorical endpoints, standard descriptive statistics, including frequency table and exact 95% confidence intervals will be computed using the Clopper-Pearson method.
- Incidence of adverse events [ Time Frame: For up to 1 year ]For categorical endpoints, standard descriptive statistics, including frequency table and exact 95% confidence intervals will be computed using the Clopper-Pearson method.
- Symptom burden and health status [ Time Frame: For up to 1 year ]Will be assessed by the MD Anderson Symptom Inventory (MDASI) ."For categorical endpoints, standard descriptive statistics, including frequency table and exact 95% confidence intervals will be computed using the Clopper-Pearson method.
- Progression-free survival [ Time Frame: Up to 1 year ]Summarized using descriptive statistics, including Kaplan-Meier curve and estimates.
- Symptom burden and health status [ Time Frame: For up to 1 year ]Will be assessed by EuroQol 5-dimension. For categorical endpoints, standard descriptive statistics, including frequency table and exact 95% confidence intervals will be computed using the Clopper-Pearson method.
- Symptom burden and health status [ Time Frame: For up to 1 year ]Will be assessed by 5-level (EQ-5D-5L) instruments. For categorical endpoints, standard descriptive statistics, including frequency table and exact 95% confidence intervals will be computed using the Clopper-Pearson method.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||Female|
|Accepts Healthy Volunteers:||No|
- Written informed consent and any locally-required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA] in the United States of America [USA]) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
- Histology showing high-grade epithelial non-mucinous ovarian, primary peritoneal, or fallopian tube cancer
- Documented BRCA pathway mutations
- No prior treatment for primary advanced (stage III or IV) epithelial ovarian, primary peritoneal, or fallopian tube carcinoma such as irradiation, chemotherapy, hormonal therapy, immunotherapy, investigational therapy, surgery, and/or other concurrent agents or therapies
- A disposition to neoadjuvant chemotherapy (NACT) with planned interval tumor reductive surgery after 3 complete cycles of treatment
- Have measurable disease based on RECIST version 1.1 or evaluable disease. Measurable disease is defined at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each "target" lesion must be > 20 mm when measured by conventional techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic resonance imaging (MRI), or > 10 mm when measured by spiral CT. Evaluable disease includes nonmeasurable lesions, ascites, pleural effusion
- Peripheral neuropathy grade 0 or 1 by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy of >= 16 weeks
- Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1. Postmenopausal is defined as: amenorrheic for 1 year or more following cessation of exogenous hormonal treatments, luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the postmenopausal range for women under 50, radiation-induced oophorectomy with last menses > 1 year ago, chemotherapy-induced menopause with > 1 year interval since last menses, or surgical sterilization (bilateral oophorectomy or hysterectomy). Women of childbearing potential (WoCBP) must utilize acceptable contraception for two weeks before the first dose of olaparib, for the duration of the study, and for at least 6 months after the last dose of olaparib
- Hemoglobin >= 10.0 g/dL (with no blood transfusion in the past 28 days) (measured within 28 days prior to administration of study treatment)
- Absolute neutrophil count (ANC) >= 1.5 x 109/L (> 1500 per mm3) (measured within 28 days prior to administration of study treatment)
- Platelet count >= 100 x 109/L (> 100,000 per mm3) (measured within 28 days prior to administration of study treatment)
- Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN) (measured within 28 days prior to administration of study treatment)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN unless liver metastases are present, in which case it must be =< 5 x ULN (measured within 28 days prior to administration of study treatment)
- Serum creatinine clearance (CrCL) >= 51 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of CrCL (measured within 28 days prior to administration of study treatment)
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Previous enrollment in the present study
- Prior treatment for ovarian, fallopian tube, or primary peritoneal cancer
- Histology showing mucinous or low grade epithelial carcinoma
- Participation in another clinical study with an investigational product (IP) during the last 4 weeks
- History of another primary malignancy except for: malignancy treated with curative intent and with no known active disease >= 5 years before the first dose of study drug and of low potential risk for recurrence, adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, and/or adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ
- Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, mean QT interval corrected for heart rate with Fridericia's correction (QTcF) prolongation > 500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome
- Any unresolved toxicity (> CTCAE grade 2) from previous anti-cancer therapy, excluding alopecia
- History of hypersensitivity to olaparib or its excipients
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV) or otherwise immunocompromised subjects, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
- History of leptomeningeal carcinomatosis
- Subjects who are pregnant and/or breast-feeding
- Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of subject safety or study results
- Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids. The subject can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
- Subjects with uncontrolled seizures
- Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML)
- Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
- Any previous treatment with PARP inhibitor, including olaparib
- Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks
- Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's wort ) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
- Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
- Previous allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
- Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable outside of 28 days prior to treatment)
- Non-English speakers will be excluded from participating in the patient-reported outcomes component of the study
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03943173
|Contact: Shannon N Westinfirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Shannon N. Westin 713-794-4314|
|Principal Investigator: Shannon N. Westin|
|Principal Investigator:||Shannon N Westin||M.D. Anderson Cancer Center|
|Responsible Party:||M.D. Anderson Cancer Center|
|Other Study ID Numbers:||
NCI-2019-00503 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2018-0775 ( Other Identifier: M D Anderson Cancer Center )
|First Posted:||May 9, 2019 Key Record Dates|
|Last Update Posted:||June 1, 2022|
|Last Verified:||May 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Plan Description:||Pending discussions with AstraZeneca regarding the level and quantity of data that may be shared. Discussions will also include potential modifications of the contract to allow for data sharing.|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Neoplasms by Site
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Genital Neoplasms, Female
Endocrine System Diseases
Fallopian Tube Diseases
Digestive System Neoplasms
Digestive System Diseases
Neoplasms, Cystic, Mucinous, and Serous