Breast Cancer Clinical Trial
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
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 (metastatic) or cannot be removed by surgery (unresectable) or ovarian, fallopian tube, primary peritoneal, or triple-negative breast cancer that has come back (recurrent). Olaparib and onalespib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
I. To establish the maximum tolerated dose (MTDs) of olaparib and onalespib (AT13387) administered in combination in patients with advanced solid tumors.
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) 5.0.
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). Although the clinical benefit of [this/these] drug(s) has not yet been established, the intent of offering this treatment is to provide a possible therapeutic benefit, and thus the patient will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability.
OUTLINE: This is a dose-escalation study.
Patients receive olaparib orally (PO) twice daily (BID) on days 1-7 (cycle 0). Beginning in cycle 1, patients receive olaparib PO BID on days 1-28 and onalespib intravenously (IV) over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles 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.
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 escalation cohort, patients may have received any number of prior therapies
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 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
Because no dosing or adverse event data are currently available on the use of olaparib in combination with AT13387 in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
There must be availability of a formalin-fixed, paraffin-embedded tumor specimen
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky > 60%)
Life expectancy of greater than 12 weeks
Leukocytes >= 3,000/mcL
Hemoglobin >= 10 g/dL with no blood transfusion in the past 28 days
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]) =< 3 x institutional upper limit of normal
Creatinine =< the institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
Corrected QT using Fridericia's formula (QTcF) =< 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
The effects of olaparib in combination with AT13387on the developing human fetus are unknown; for this reason and because olaparib and AT13387 are anti-neoplastic small molecule inhibitors, which are agents that are potentially teratogenic, 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, for the duration of study participation, and for 3 months after the last dose of study drugs; 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
Ability to understand and the willingness to sign a written informed consent document
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 active or history of 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 because olaparib and AT13387 are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AT13387 or olaparib, 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 because of the potential for pharmacokinetic interactions with olaparib or AT13387; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
Known history of QT/corrected 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; the study team should check a frequently-updated medical reference for a list of drugs to avoid or minimize use of; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
Participants with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
Check Your Eligibility
Let’s see if you might be eligible for this study.
What is your age and gender ?
There are 7 Locations for this study
Phoenix Arizona, 85054, United States
Scottsdale Arizona, 85259, United States
Jacksonville Florida, 32224, United States
Boston Massachusetts, 02114, United States
Boston Massachusetts, 02115, United States
Boston Massachusetts, 02215, United States
Boston Massachusetts, 02215, United States
Rochester Minnesota, 55905, United States
How clear is this clinincal trial information?
Introducing, the Journey Bar
Use this bar to access information about the steps in your cancer journey.