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Adult Solid NeoplasmPhase 1NCT02627430

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

A Phase 1 study testing Hsp90 Inhibitor AT13387, Laboratory Biomarker Analysis and Pharmacological Study in people with Adult Solid Neoplasm and Estrogen Receptor Negative, run by National Cancer Institute (NCI).

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Hsp90 Inhibitor AT13387, Laboratory Biomarker Analysis and Pharmacological Study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Mar 2016to Mar 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Hsp90 Inhibitor AT13387, Laboratory Biomarker Analysis, Pharmacological Study, Talazoparib
Medical subject headings
Breast Neoplasms, Fallopian Tube Neoplasms, Ovarian Neoplasms, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hsp90 Inhibitor AT13387Drug

    Also called AT13387

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • TalazoparibDrug

    Also called BMN 673, BMN-673

    Given PO

Study groups in NCT02627430
Study groupRoleWhat they receive
Treatment (talazoparib and Hsp90 inhibitor AT13387)ExperimentalPatients 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.
Receives: Drug: Hsp90 Inhibitor AT13387; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Talazoparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 35 days

Secondary outcomes (2)

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

    Measured: 30 days post-treatment

  2. Pharmacokinetic (PK) parameters of talazoparib and HSP90 inhibitor AT13387

    Pearson correlation coefficients, presented with 95% confidence intervals, will be used to investigate the association of the percent change heat shock protein 90 and poly(adenosine diphosphate-ribose) polymerase 1 activities with PK parameters, including maximum concentration observed and area under the curve.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Dec 2015 (estimated)
  2. Study startMar 2016
  3. Primary completionMar 2019 (estimated)

Why it stopped: Other - Protocol moved to Withdrawn

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02627430
Sponsor's protocol ID
NCI-2015-02063
Other IDs
NCI-2015-02063, 9896, 9896, P30CA006516, UM1CA186709
Status last verified
Jul 2016
First submitted
9 Dec 2015
Last updated
26 Jul 2016
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Hsp90 Inhibitor AT13387, Laboratory Biomarker Analysis and Pharmacological Study in people with Adult Solid Neoplasm and Estrogen Receptor Negative, run by National Cancer Institute (NCI).

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 26 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MTD based on the dose-limiting toxicity based on the National Cancer Institute (NCI) CTCAE v. 4.0 (time frame: 35 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02627430.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2016.

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