Brief Title
Talazoparib and HSP90 Inhibitor AT13387 in Treating Patients With Metastatic Advanced Solid Tumor or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple Negative Breast Cancer
Official Title
A Phase 1 Study of PARP Inhibitor BMN 673 and HSP90 Inhibitor AT13387 for Treatment of Advanced Solid Tumors With Expansion in Patients With Recurrent Epithelial Ovarian, Fallopian Tube, Peritoneal Cancer or Recurrent Triple-Negative Breast Cancer
Brief Summary
This phase I trial studies the side effects and best dose of talazoparib and heat shock
protein (HSP)90 inhibitor AT13387 when given together in treating patients with solid tumors
that have spread to other places in the body (metastatic) or ovarian, fallopian tube, primary
peritoneal, or hormone negative breast cancer that have come back after a period of
improvement (recurrent). Talazoparib and HSp90 inhibitor AT13387 may stop the growth of tumor
cells by blocking some enzymes that are need for cell growth. HSp90 inhibitor AT1338 may also
help talazoparib work better by making tumor cells more sensitive to the drug.
Detailed Description
PRIMARY OBJECTIVES:
I. To establish the maximum tolerated dose (MTDs) of BMN673 (talazoparib) and AT13387 (HSP90
Inhibitor AT13387) administered in combination in patients with advanced solid tumors.
SECONDARY OBJECTIVES:
I. To identify the dose-limiting toxicity (DLT) and other toxicities associated with BMN673
and AT13387 administered in combination as assessed by Common Terminology Criteria for
Adverse Events (CTCAE) version (v) 4.0.
II. To determine the recommended phase 2 doses (RP2D) of the combination of BMN673 and
AT13387.
III. To determine the plasma pharmacokinetics of BMN673 and AT13387. IV. To document
anti-tumor activity of the combination of BMN673 and AT13387 as assessed by (Response
Evaluation Criteria in Solid Tumors (RECIST) 1.1 and progression free survival (PFS).
OUTLINE: This is a dose-escalation study.
Patients receive talazoparib orally (PO) once daily (QD) on days 1-7 (course 0). Beginning in
course 1, patients receive talazoparib PO QD on days 1-28 and HSP90 inhibitor AT13387
intravenously (IV) over 1 hour on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days
in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days and then every 3
months for up to 2 years.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
MTD based on the dose-limiting toxicity based on the National Cancer Institute (NCI) CTCAE v. 4.0
Secondary Outcome
Incidence of adverse events as assessed by NCI CTCAE v. 4.0
Condition
Adult Solid Neoplasm
Intervention
Hsp90 Inhibitor AT13387
Study Arms / Comparison Groups
Treatment (talazoparib and Hsp90 inhibitor AT13387)
Description: Patients receive talazoparib PO QD on days 1-7 (course 0). Beginning in course 1, patients receive talazoparib PO QD on days 1-28 and HSP90 inhibitor AT13387 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
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
0
Start Date
March 2016
Primary Completion Date
March 2019
Eligibility Criteria
Inclusion Criteria:
- For the dose escalation cohort, patients must have histologically or cytologically
confirmed malignancy that is metastatic or unresectable and for which standard
curative or palliative measures do not exist or are no longer effective
- For the dose expansion cohort, participants must have histologically or cytologically
confirmed diagnosis of either: i) ovarian, fallopian tube, or primary peritoneal
cancer of high grade serous histology which has recurred despite standard therapy or
ii) triple-negative breast cancer which has recurred despite standard therapy
- There is no line limit for the dose escalation cohort and the dose expansion cohort
- For the dose expansion cohort, patients with ovarian, fallopian tube or primary
peritoneal cancer must have platinum resistant disease defined as progression within 6
months after last platinum regimen; platinum refractory disease is allowed
- For the dose expansion cohort, patients with triple-negative breast cancer may not be
breast cancer 1/2 (BRCA1/2) germline mutation carriers
- There must be availability of a formalin-fixed, paraffin-embedded tumor specimen with
adequate viable tumor tissue
- Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky > 60)
- Life expectancy of greater than 12 weeks
- Leukocytes >= 3,000/mcL
- Hemoglobin >= 9 g/dL
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
= < 2.5 × institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance >= 60
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Left ventricular ejection fraction > 50% on echocardiography or multigated acquisition
(ECHO/MUGA) scan
- Corrected QT (QTc) =< 450 ms
- Any clinically significant electrolyte imbalance, particularly hypokalemia and
hypomagnesemia, should be corrected before treatment
- Have undergone clearance after baseline ophthalmologic exam (at least fundoscopic
exam, visual acuity, intraocular pressure, assessment of visual fields and measurement
of color vision)
- For the expansion cohort only: measurable disease by RECIST v1.1 with at least one
measurable target lesion
- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
the duration of study participation; should a woman become pregnant or suspect she is
pregnant while she or her partner is participating in this study, she should inform
her treating physician immediately; men treated or enrolled on this protocol must also
agree to use adequate contraception prior to the study, for the duration of study
participation, and 4 months after completion of BMN 673 and/or AT13387 administration
- Patients must be able to swallow pills and have no significant impairment in
gastrointestinal absorption
- Three biopsies, one pretreatment, one after BMN673 alone and one after one of the
combinations of BMN673/AT13387 will be voluntary in the expansion and dose escalation
cohorts; however, biopsies will be required in at least 8 patients of the 20 patients
to be enrolled in the expansion cohort
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier
- All acute, clinically significant treatment-related toxicity from prior therapy,
except for alopecia, must have resolved to grade =< 1
- Patients who are receiving any other investigational agents
- Patients with known brain metastases should be excluded from this clinical trial
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to BMN 673 and AT13387 used in study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with BMN 673 or AT13387
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible
- Known history of QT/QTc prolongation or torsades de pointes (TdP); patients who are
currently receiving treatment with medication with a known risk to prolong the QT
interval or inducing torsades de pointes and the treatment cannot either be
discontinued or switched to a different medication prior to starting study drugs
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Panagiotis Konstantinopoulos, ,
Administrative Informations
NCT ID
NCT02627430
Organization ID
NCI-2015-02063
Secondary IDs
NCI-2015-02063
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Panagiotis Konstantinopoulos, Principal Investigator, Dana-Farber - Harvard Cancer Center LAO
Verification Date
July 2016