BMN 673 (Talazoparib), an Oral PARP Inhibitor, in People With Deleterious BRCA1/2 Mutation-Associated Ovarian Cancer Who Have Had Prior PARP Inhibitor Treatment

NCT02326844 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 15005015-C-0050
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- The new drug BMN 673 (talazoparib) has been shown to fight tumor cells in animals and some people. It is a poly (ADP-ribose) polymerase (PARP) inhibitor. It works on tumor cell deoxyribonucleic acid (DNA) damage repair process. Researchers want to see if BMN 673 shrinks cancer again in women with ovarian cancer and whose cancer initially got shrunk but grew back on the first PARP inhibitor. Objective: \- To study BMN 673 (talazoparib) in people with ovarian cancer born with a breast cancer (BRCA) mutation and whose cancer got shrunk but became worse after they took a similar drug. Eligibility:

• Women at least 18 years old:
• with recurrent and/or metastatic germline breast cancer mutation (gBRCAm)-associated ovarian cancer AND
• whose disease is growing after already being treated with PARP inhibitors AND
• with no other treatment(s) in between the first PARP inhibitors and a screening visit. Design:
• Participants will be screened with medical history, physical exam, and heart and blood tests.
• Participants will take the study drug by mouth once daily. They will take the drug in 28-day cycles.
• They will keep a diary of doses and any side effects.
• Participants will have 4 study visits in cycle 1, then 1 visit every cycle. Visits may include:
• Blood tests
• Physical exam
• Computed tomography (CT) or magnetic resonance imaging (MRI) scans. Participants will lie in a machine that takes pictures of their body.
• Ultrasound
• Participants will have a biopsy before starting the study drug. A small piece of tumor tissue will be removed by needle, guided by a scan. They may have two more biopsies later.
• Participants will be followed for 30 days after taking the last dose of study drug. A physical exam, blood tests, and CT or other scans will be done.
• Participants will have follow-up calls to ask about any side effects.

Conditions

Ovarian Cancer

Keywords

Germline BRCA1/2 Mutations (gBRCAm); DNA Damaging Agents; FOX03a, 53BP1 and RAD51

Outcome Measures

Primary Outcomes (1)

• Objective Response (Complete Response (CR) + Partial Response (PR))

  Objective response (complete response (CR) + partial response (PR)) was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  Every 2 cycles, an average of 64 days

Secondary Outcomes (3)

• Number of Participants With Serious and Non-serious Adverse Events

  15 months

• Duration of Response

  3 months

• Progression Free Survival (PFS) on BMN673 (Talazoparib) to PFS From First Poly (ADP-ribose) Polymerase Inhibitor (PARPPi) Exposure

  3 months

Other Outcomes (2)

• Forkhead Box 03 (FOXO3a), p53-binding Protein 1 (53BP1) and RAD51 (i.e., Eukaryote Gene) Biomarkers

  Baseline

• Secondary Mutation of Breast Cancer 1 (BRCA1) and Breast Cancer 2 (BRCA2)

  Baseline

Study Arms (1)

Ovarian Cancer Patients

EXPERIMENTAL

Ovarian cancer patients with germline breast cancer mutation (gBRCAm) who have progressed on prior poly (ADP-ribose) polymerase inhibitor (PARPi) therapy

Drug: BMN 673 (talazoparib)

Interventions

BMN 673 (talazoparib) DRUG

1 mg by mouth (p.o.) once daily on 28-day cycles until disease progression

Also known as: talazoparib

Ovarian Cancer Patients

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recurrent, and/or metastatic germline breast cancer (BRCA) 1/2 mutation-associated ovarian cancer, with progression on a poly (ADP-ribose) polymerase (PARP) inhibitor monotherapy after attaining a response to that PARPi (complete response (CR), partial response (PR), or stable disease (SD) greater than or equal to 4mo)
• Progression should have occurred within the immediate prior 2 months of the time of screening visit, with no intervening anti-cancer therapy.
• Patients must be at least 4 weeks from the last dose of prior PARP inhibitor.
• All patients must have at least one lesion deemed safe to biopsy and be willing to undergo mandatory baseline biopsy. It is preferred that this lesion be a lesion that progressed or arose while on the prior PARP therapy.
• Histopathologic diagnosis of ovarian cancer (including primary peritoneal and fallopian tube cancers) must be confirmed in the Laboratory of Pathology, National Cancer Institute (NCI).
• Age greater than or equal to18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60%.
• Patients must have normal organ and marrow function as defined below:
• absolute neutrophil count greater than or equal to 1,500/mcL
• platelets greater than or equal to100,000/mcL
• total bilirubin less than or equal to 1.5X upper limit of normal, unless known Gilberts syndrome
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase (SGPT) less than or equal to 3 x institutional upper limit of normal
• creatinine \< 1.5 X upper limit of normal
• measured creatinine clearance \>60 mL/min/1.73 m(2) for patients with serum creatinine levels \> 1.5 x upper limit of normal.
• hemoglobin greater than or equal to 10 mg/dL (in the absence of transfusion within 24 hours prior to dosing).

You may not qualify if:

• Patients who have had prior BMN 673 (talazoparib) therapy.
• Patients with known brain metastases diagnosed within 1 year will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Exception: patients with brain metastases diagnosed greater than 1 year prior to study entry may be considered if they received sterilizing therapy to the central nervous system (CNS) (resection or radiation) and have been CNS progression-free for the 1-year period.
• Lack of recovery of prior cancer therapy-related adverse events to Grade less than or equal to 1 (National Cancer Institute (NCI) Common Terminology Criteria in Adverse Events (CTCAE) v4.03; except alopecia). Stable persistent grade 2 peripheral neuropathy may be allowed as determined on a case-by-case basis at the discretion of the PI. Patients with platinum-related grade 2 or greater hypomagnesemia (on replacement) will be eligible.
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, clinically significant gastrointestinal (GI) bleeding or hemoptysis within 28 days prior to the start of the study, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with active infection will not be eligible, but may become eligible once infection has resolved and they are at least 7 days from completion of antibiotics.
• Another previous or current invasive malignancy within the last 2 years, with the exception of curatively treated stage Ia cervical carcinoma, or resected stage Ia endometrial cancer, and noninvasive nonmelanoma skin cancers.
• Human immunodeficiency virus (HIV)- positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with BMN 673 (talazoparib). HIV- positive patients who are not on combination antiretroviral therapy (cART) and have cluster of differentiation 4 (CD4) counts \> 500 are eligible.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to BMN 673 (talazoparib)
• Patients who are receiving any other investigational or commercial agents with the intent to treat the malignancy.
• Patients with gastrointestinal conditions that might predispose for drug intolerability or poor drug absorption.
• Use of nasogastric or gastric (G)-tube administration.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Lee JM, Hays JL, Annunziata CM, Noonan AM, Minasian L, Zujewski JA, Yu M, Gordon N, Ji J, Sissung TM, Figg WD, Azad N, Wood BJ, Doroshow J, Kohn EC. Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. J Natl Cancer Inst. 2014 May 19;106(6):dju089. doi: 10.1093/jnci/dju089. Print 2014 Jun.

  PMID: 24842883 BACKGROUND

• O'Sullivan CC, Moon DH, Kohn EC, Lee JM. Beyond Breast and Ovarian Cancers: PARP Inhibitors for BRCA Mutation-Associated and BRCA-Like Solid Tumors. Front Oncol. 2014 Feb 28;4:42. doi: 10.3389/fonc.2014.00042. eCollection 2014.

  PMID: 24616882 BACKGROUND

• Lee JM, Ledermann JA, Kohn EC. PARP Inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies. Ann Oncol. 2014 Jan;25(1):32-40. doi: 10.1093/annonc/mdt384. Epub 2013 Nov 12.

  PMID: 24225019 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

talazoparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Results Point of Contact

• Title: Dr. Jung-Min Lee
• Organization: National Cancer Institute

leej6@mail.nih.gov

301-443-7735

Study Officials

• Jung-Min Lee, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 25, 2014
• First Posted: December 30, 2014
• Study Start: March 2, 2015
• Primary Completion: April 14, 2016
• Study Completion: April 14, 2016
• Last Updated: August 18, 2020
• Results First Posted: May 24, 2017

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)