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

NCT02627430 | Withdrawn Phase 1

• 4 other identifiers: NCI-2015-020639896P30CA006516UM1CA186709
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Adult Solid Neoplasm; Estrogen Receptor Negative; Fallopian Tube Serous Neoplasm; HER2/Neu Negative; Ovarian Serous Adenocarcinoma; Ovarian Serous Tumor; Primary Peritoneal Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• MTD based on the dose-limiting toxicity based on the National Cancer Institute (NCI) CTCAE v. 4.0

  DLT defined as non-hematologic and hematologic toxicities experienced during course 0 and the first course (i.e. first 4 weeks) of treatment.

  35 days

Secondary Outcomes (2)

• Incidence of adverse events as assessed by NCI CTCAE v. 4.0

  30 days post-treatment

• Pharmacokinetic (PK) parameters of talazoparib and HSP90 inhibitor AT13387

  Baseline, at 1, 2, 4 and 8 hours of day 1 (course 0), baseline of days 1, 8, and 15 of course 1, and at 1, 2, 4, and 8 hours post-dosing on day 8 and 15 of course 1

Other Outcomes (5)

• Change in BRCA1 foci expression in tumor tissue via IHC

  Baseline to day 15 of course 1

• Change in BRCA1 foci expression in tumor tissue via immunohistochmestry (IHC)

  Baseline to day 7 of course 0

• Change in heat shock protein 70 (HSPT70) expression

  Day 7 (course 0) to day 15 (course 1)

Study Arms (1)

Treatment (talazoparib and Hsp90 inhibitor AT13387)

EXPERIMENTAL

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.

Drug: Hsp90 Inhibitor AT13387; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Talazoparib

Interventions

Hsp90 Inhibitor AT13387 DRUG

Given IV

Also known as: AT13387

Treatment (talazoparib and Hsp90 inhibitor AT13387)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (talazoparib and Hsp90 inhibitor AT13387)

Pharmacological Study OTHER

Correlative studies

Treatment (talazoparib and Hsp90 inhibitor AT13387)

Talazoparib DRUG

Given PO

Also known as: BMN 673, BMN-673

Treatment (talazoparib and Hsp90 inhibitor AT13387)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Conditions

Breast Neoplasms; Fallopian Tube Neoplasms; Ovarian Neoplasms; Triple Negative Breast Neoplasms

Interventions

(2,4-dihydroxy-5-isopropylphenyl)-(5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl)methanone; talazoparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Panagiotis Konstantinopoulos

  Dana-Farber - Harvard Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2015
• First Posted: December 11, 2015
• Study Start: March 1, 2016
• Primary Completion: March 1, 2019
• Last Updated: July 26, 2016

Record last verified: 2016-07