Clinical trial NCT02316834: Talazoparib in Determining Genetic Effects on Disease Response in Patients With Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Official title: POSITION: A Pilot Study of Induction PARP Inhibition in Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: 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
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-12-15
Enrollment: 4
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Change in deoxyribonucleic acid (DNA) copy number
timeFrame: Baseline to the day of tumor reductive surgery
measure: Change in ribonucleic acid (RNA) protein expression
timeFrame: Baseline to the day of tumor reductive surgery
Secondary outcomes:
measure: Overall survival
timeFrame: Up to 3 years
measure: Tumor response
timeFrame: Up to 30 days
measure: Tumor volume
timeFrame: Up to 30 days
measure: Apoptosis
timeFrame: Up to 30 days
measure: Completion Rate of BMN 673 to determine feasibility
timeFrame: Up to 30 days
measure: Incidence of adverse events
timeFrame: Up to 30 days
measure: Proportion of patients that exhibit an increase (or decrease) in RNA protein expression greater than 50%
timeFrame: Baseline to the day of tumor reductive surgery
measure: Change in DNA copy number
timeFrame: Baseline to the day of tumor reductive surgery
measure: Change in RNA protein expression
timeFrame: Baseline to the day of tumor reductive surgery
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: The Woman's Hospital of Texas
state: Texas
city: Houston
country: United States
facility: MD Anderson Regional Care Center-Katy
state: Texas
city: Nassau Bay
country: United States
facility: MD Anderson Regional Care Center-Bay Area
state: Texas
city: Sugar Land
country: United States
facility: MD Anderson Regional Care Center-Sugar Land
state: Texas
city: The Woodlands
country: United States
facility: MD Anderson Regional Care Center-The Woodlands
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Shannon Westin
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sun C, Fang Y, Labrie M, Li X, Mills GB. Systems approach to rational combination therapy: PARP inhibitors. Biochem Soc Trans. 2020 Jun 30;48(3):1101-1108. doi: 10.1042/BST20191092.