Clinical Trials /

Olaparib and Onalespib in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple-Negative Breast Cancer

NCT02898207

Description:

This phase I trial studies the side effects and best dose of olaparib and onalespib when given together in treating patients with solid tumors that have spread to other places in the body or cannot be removed by surgery or ovarian, fallopian tube, primary peritoneal, or triple-negative breast cancer that has come back. Olaparib and onalespib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Breast Carcinoma
  • Fallopian Tube Carcinoma
  • Malignant Ovarian Epithelial Tumor
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title:Olaparib and Hsp90 Inhibitor AT13387 in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple-Negative Breast Cancer
  • Official Title:A Phase 1 Study of PARP Inhibitor Olaparib 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

Clinical Trial IDs

  • ORG STUDY ID: NCI-2016-01364
  • SECONDARY ID: NCI-2016-01364
  • SECONDARY ID: 10031
  • SECONDARY ID: 10031
  • SECONDARY ID: P30CA006516
  • SECONDARY ID: UM1CA186709
  • NCT ID: NCT02898207

Trial Conditions

  • Estrogen Receptor Negative
  • HER2/Neu Negative
  • High Grade Fallopian Tube Serous Adenocarcinoma
  • High Grade Ovarian Serous Adenocarcinoma
  • Metastatic Solid Neoplasm
  • Primary Peritoneal High Grade Serous Adenocarcinoma
  • Progesterone Receptor Negative
  • Recurrent Breast Carcinoma
  • Recurrent Fallopian Tube Carcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma
  • Triple-Negative Breast Carcinoma
  • Unresectable Solid Neoplasm

Trial Interventions

DrugSynonymsArms
Hsp90 Inhibitor AT13387AT13387Treatment (olaparib and Hsp90 inhibitor AT13387)
OlaparibAZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281Treatment (olaparib and Hsp90 inhibitor AT13387)

Trial Purpose

This phase I trial studies the side effects and best dose of olaparib and Hsp90 inhibitor AT13387 when given together in treating patients with solid tumors that have spread to other places in the body or cannot be removed by surgery or ovarian, fallopian tube, primary peritoneal, or triple-negative breast cancer that has come back. Olaparib and Hsp90 inhibitor AT13387 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES:

I. To establish the maximum tolerated dose (MTDs) of olaparib and Hsp90 inhibitor AT13387 (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 olaparib 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 olaparib and AT13387.

III. To determine the plasma pharmacokinetics of olaparib and AT13387. IV. To document anti-tumor activity of the combination of olaparib 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 olaparib orally (PO) twice daily (BID) on days 1-7 (course 0). Beginning in course 1, patients receive olaparib PO BID 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 at 30 days and every 3 months for up to 2 years.

Trial Arms

NameTypeDescriptionInterventions
Treatment (olaparib and Hsp90 inhibitor AT13387)ExperimentalPatients receive olaparib PO BID on days 1-7 (course 0). Beginning in course 1, patients receive olaparib PO BID 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.
  • Hsp90 Inhibitor AT13387
    • Olaparib

    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:

    - Ovarian, fallopian tube, or primary peritoneal cancer of high grade serous histology which has recurred despite standard therapy; up to 3 prior lines in the platinum resistant setting (i.e. up to 3 lines after patients have become platinum resistant); patients may have received unlimited lines while platinum sensitive

    - Triple-negative breast cancer (TNBC) which has recurred despite standard therapy; recurrent TNBC needs to have metastatic disease and patients with an in breast recurrence are not eligible; up to 4 prior lines in the recurrent setting for patients with triple-negative breast cancer are allowed; for the ovarian cancer, there will be up to 3

    - For the dose escalation cohort, patients may have received any number of prior therapies and be eligible for this study

    - 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 BRCA1/2 germline mutation carriers

    - There must be availability of a formalin-fixed, paraffin-embedded tumor specimen

    - 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 x 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

    - Corrected QT (QTc) =< 450 ms

    - Any clinically significant electrolyte imbalance, particularly hypokalemia and hypomagnesemia, should be corrected before treatment

    - Pre-study evaluation must include an ophthalmologic exam by an ophthalmologist (not optometrist) and should minimally include visual acuity testing, slit lamp examination, and funduscopic examination; follow up eye-exams will only be performed if subjects develop/report any visual impairment; visual impairment may include peripheral flashes (photopsia), blurred or double vision, floaters, color distortion and dimness, difficulties with light/dark accommodation, tunnel vision or other field defects, halos, apparent movement of stationary objects, and complex disturbances; follow up eye-exams will minimally include visual acuity testing, slit lamp examination, and funduscopic examination; additional testing will be based on symptoms, what is observed and ophthalmologist recommendations

    - 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 olaparib and/or AT13387 administration

    - Patients must be able to swallow tablets and have no significant impairment in gastrointestinal absorption

    - Three biopsies, one pretreatment, one after olaparib alone and one after one of the combinations of olaparib/AT13387 will be voluntary, but encouraged in the expansion and dose escalation cohorts

    - 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 because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events

    - History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib 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 olaparib 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

    - Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 or moderate inhibitors of CYP3A4 are ineligible

    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Both
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:MTD defined as the highest dose at which 0 of 3 or 1 of 6 or fewer patients experience a DLT based on the National Cancer Institute (NCI) CTCAE, v 4.0
    Time Frame:Up to 35 days
    Safety Issue:Yes
    Description:

    Secondary Outcome Measures

    Trial Keywords