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Talazoparib in Determining Genetic Effects on Disease Response in Patients With Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (POSITION)

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ClinicalTrials.gov Identifier: NCT02316834
Recruitment Status : Active, not recruiting
First Posted : December 15, 2014
Last Update Posted : May 22, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This pilot early phase I trial studies talazoparib to determine if certain characteristics of the deoxyribonucleic acid (DNA) affect how the disease responds to therapy in patients with ovarian, fallopian tube, or primary peritoneal cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Studying samples of tissue in the laboratory from patients receiving talazoparib may help doctors learn more about the effects of talazoparib on cells and may help doctors understand how well patients respond to treatment.

Condition or disease Intervention/treatment Phase
Fallopian Tube Serous Adenocarcinoma High Grade Ovarian Serous Adenocarcinoma Ovarian Mass Primary Peritoneal Serous Adenocarcinoma Stage III Fallopian Tube Cancer AJCC v7 Stage III Ovarian Cancer AJCC v6 and v7 Stage III Primary Peritoneal Cancer AJCC v7 Stage IIIA Fallopian Tube Cancer AJCC v7 Stage IIIA Ovarian Cancer AJCC v6 and v7 Stage IIIA Primary Peritoneal Cancer AJCC v7 Stage IIIB Fallopian Tube Cancer AJCC v7 Stage IIIB Ovarian Cancer AJCC v6 and v7 Stage IIIB Primary Peritoneal Cancer AJCC v7 Stage IIIC Fallopian Tube Cancer AJCC v7 Stage IIIC Ovarian Cancer AJCC v6 and v7 Stage IIIC Primary Peritoneal Cancer AJCC v7 Stage IV Fallopian Tube Cancer AJCC v6 and v7 Stage IV Ovarian Cancer AJCC v6 and v7 Stage IV Primary Peritoneal Cancer AJCC v7 Other: Laboratory Biomarker Analysis Drug: BMN 673 Early Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. To explore basal levels and effects of talazoparib (BMN 673) on DNA copy number, loss of heterozygosity and mutation, and level of ribonucleic acid (RNA) and protein expression (together described as "molecular results") in homologous recombination-related pathways before and after treatment in women with primary advanced high grade serous ovarian, fallopian tube, or primary peritoneal cancer.

SECONDARY OBJECTIVES:

I. To correlate molecular results to clinical endpoints including response and survival.

II. To correlate molecular results to pathologic endpoints including tumor volume and apoptosis.

III. To compare DNA copy number and level of RNA and protein expression in homologous recombination-related pathways in tissue from patients treated with BMN 673 to those untreated with BMN 673 in the preoperative period.

IV. To determine the toxicity of daily BMN 673 given preoperatively, with a focus on postoperative wound healing.

V. To determine feasibility of daily BMN 673 given preoperatively.

OUTLINE:

Patients receive talazoparib orally (PO) once daily (QD) for up to 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: POSITION: A Pilot Study of Induction PARP Inhibition in Ovarian Cancer
Actual Study Start Date : June 2, 2015
Estimated Primary Completion Date : February 1, 2021
Estimated Study Completion Date : February 1, 2021


Arm Intervention/treatment
Experimental: BMN 673 Other: Laboratory Biomarker Analysis
Correlative studies

Drug: BMN 673

BMN673 given at a dose of 1 mg orally once daily.

Participants begin taking BMN 673 tablets by mouth every day, starting on the day of scheduled laparoscopy. Participants take the study drug for at least 7 days before scheduled tumor reduction surgery.

Other Name: TALAZOPARIB




Primary Outcome Measures :
  1. Change in deoxyribonucleic acid (DNA) copy number [ Time Frame: Baseline to the day of tumor reductive surgery ]
    Will use descriptive statistics and graphical methods to summarize the change in DNA copy number. Will summarize these changes for untreated patients. Will use a paired t-test to test that mean changes are different from 0. Will test median changes with a Wilcoxon signed-rank test. Will use a 2-sample t-test to compare mean changes between treated and untreated patients. Will compare median changes between treated and untreated patients with a Wilcoxon rank sum test.

  2. Change in ribonucleic acid (RNA) protein expression [ Time Frame: Baseline to the day of tumor reductive surgery ]
    Will use descriptive statistics and graphical methods to summarize the change in RNA protein expression. Will summarize these changes for untreated patients. Will use a paired t-test to test that mean changes are different from 0. Will test median changes with a Wilcoxon signed-rank test. Will use a 2-sample t-test to compare mean changes between treated and untreated patients. Will compare median changes between treated and untreated patients with a Wilcoxon rank sum test. Will use McNemar's test to compare the changes based on homologous recombination deficiency (HRD) assay results.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: Up to 3 years ]
    Will use Cox proportional hazards regression methods to model overall survival as a function of DNA copy number, changes in RNA protein expression, and HRD assay result.

  2. Tumor response [ Time Frame: Up to 30 days ]
    Will use logistic regression methods to model tumor response as a function of changes in DNA copy number, changes in RNA protein expression, and HRD assay result.

  3. Tumor volume [ Time Frame: Up to 30 days ]
    Will use linear regression methods to model tumor volume as a function of changes in DNA copy number, changes in RNA protein expression, and HRD assay result.

  4. Apoptosis [ Time Frame: Up to 30 days ]
    Will use linear regression methods to model apoptosis as a function of changes in DNA copy number, changes in RNA protein expression, and HRD assay result.

  5. Completion Rate of BMN 673 to determine feasibility [ Time Frame: Up to 30 days ]
    Treatment with BMN 673 considered feasible if 70% of patients complete all planned doses of talazoparib and post-operative chemotherapy.

  6. Incidence of adverse events [ Time Frame: Up to 30 days ]
    Will tabulate toxicities by grade and relationship to treatment.

  7. Proportion of patients that exhibit an increase (or decrease) in RNA protein expression greater than 50% [ Time Frame: Baseline to the day of tumor reductive surgery ]
    Will use Fisher's exact test to compare treated and untreated patients with respect to the proportion of patients that exhibit an increase (or decrease) in RNA protein expression. Will compare the mean change in RNA protein expression between those patients with and without a HRD on assay at baseline using a 2-sample t-test. Will compare the median changes between these 2 groups of patients with a Wilcoxon rank sum test. Will compare these 2 groups of patients with respect to HRD assay result using Fisher's exact test.

  8. Change in DNA copy number [ Time Frame: Baseline to the day of tumor reductive surgery ]
    Will use Fisher's exact test to compare treated and untreated patients with respect to the increase (or decrease) in DNA copy number. Will compare the mean change in DNA copy number between those patients with and without a HRD on assay at baseline using a 2-sample t-test. Will compare the median changes between these 2 groups of patients with a Wilcoxon rank sum test. Will compare these 2 groups of patients with respect to HRD assay result using Fisher's exact test.

  9. Change in RNA protein expression [ Time Frame: Baseline to the day of tumor reductive surgery ]
    Will use Fisher's exact test to compare treated and untreated patients with respect to the increase (or decrease) in RNA protein expression. Will compare the mean change in RNA protein expression between those patients with and without a HRD on assay at baseline using a 2-sample t-test. Will compare the median changes between these 2 groups of patients with a Wilcoxon rank sum test. Will compare these 2 groups of patients with respect to HRD assay result using Fisher's exact test.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with presumed advanced-stage high grade serous ovarian, fallopian tube, or primary peritoneal carcinoma, based on the presence of carcinomatosis, and/or elevated cancer antigen 125 (CA125), and/or ovarian mass(es), or at the discretion of the treating physician
  • Medically able to undergo primary cytoreductive surgery, at least 7 days and up to 28 days after starting study drug, as determined by treating physician
  • No prior therapy for high-grade serous ovarian, fallopian tube, or primary peritoneal carcinoma
  • Patients must be able to swallow and tolerate oral medications and not have gastrointestinal illnesses that would preclude absorption of BMN 673 (e.g. uncontrolled nausea, vomiting, or diarrhea; malabsorption syndrome; ulcerative disease)
  • Absolute neutrophil count >= 1,500/mcL (measured within 28 days prior to entry/ randomization)
  • Hemoglobin >= 9 gm/dL (measured within 28 days prior to entry/ randomization)
  • Platelets >= 100,000/mcL (measured within 28 days prior to entry/ randomization)
  • Total bilirubin =< 1.5 X upper limit of normal (ULN) (measured within 28 days prior to entry/ randomization)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal unless the liver is involved with tumor, in that case, ALT/AST must be =< 5 x upper limit of normal (measured within 28 days prior to entry/ randomization)
  • Creatinine clearance >= 50 mL/min (assessed by Cockcroft Gault estimation) (measured within 28 days prior to entry/ randomization)
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Women of child-bearing potential and their partners must agree to use contraception (hormonal or barrier method of birth control; abstinence) from the time of study entry until 30 days after the last dose of study medication; women of child-bearing potential (intact uterus) should have a negative serum pregnancy test; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; female patients must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:

    • Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 consecutive months following cessation of all exogenous hormonal treatments
    • Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, but not tubal ligation; male partners should be instructed to use contraception during the study period
  • Women must not breast-feed while taking the study medications
  • Patients must be able to understand and willing to sign an informed consent

Exclusion Criteria:

  • Prior treatment for ovarian, fallopian tube, or primary peritoneal cancer
  • Receipt of any other investigational agents or any additional anti-cancer agents
  • Significant symptom burden from presumed diagnosis including large volume ascites, pain requiring narcotic medication, or shortness of breath on exertion
  • Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication
  • As judged by the investigator, any evidence of severe or uncontrolled systemic diseases (e.g., severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung disease], uncontrolled chronic renal diseases [glomerulonephritis, nephritic syndrome, Fanconi syndrome or renal tubular acidosis]), or current unstable or uncompensated respiratory or cardiac conditions, or uncontrolled hypertension (blood pressure >= 140/90), active bleeding diatheses or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus; screening for chronic conditions is not required
  • As judged by the investigator, the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions, and requirements

Information from the National Library of Medicine

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): NCT02316834


Locations
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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
The Woman's Hospital of Texas
Houston, Texas, United States, 77054
MD Anderson Regional Care Center-Katy
Houston, Texas, United States, 77094
MD Anderson Regional Care Center-Bay Area
Nassau Bay, Texas, United States, 77058
MD Anderson Regional Care Center-Sugar Land
Sugar Land, Texas, United States, 77478
MD Anderson Regional Care Center-The Woodlands
The Woodlands, Texas, United States, 77384
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Shannon Westin M.D. Anderson Cancer Center
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02316834    
Other Study ID Numbers: 2014-0474
NCI-2014-02608 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2014-0474 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
P50CA083639 ( U.S. NIH Grant/Contract )
First Posted: December 15, 2014    Key Record Dates
Last Update Posted: May 22, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Adenocarcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Cystadenocarcinoma, Serous
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Talazoparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents