Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02898207
Other study ID # NCI-2016-01364
Secondary ID NCI-2016-0136417
Status Completed
Phase Phase 1
First received
Last updated
Start date May 19, 2017
Est. completion date January 14, 2022

Study information

Verified date April 2023
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

PRIMARY OBJECTIVE: I. To establish the maximum tolerated dose (MTDs) of olaparib and onalespib (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) 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.


Recruitment information / eligibility

Status Completed
Enrollment 28
Est. completion date January 14, 2022
Est. primary completion date July 29, 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 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 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 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)

Study Design


Related Conditions & MeSH terms

  • Adenocarcinoma
  • Breast Neoplasms
  • Carcinoma
  • Metastatic Malignant Solid Neoplasm
  • Metastatic Primary Peritoneal Serous Adenocarcinoma
  • Metastatic Triple-Negative Breast Carcinoma
  • Neoplasms
  • Platinum-Resistant Fallopian Tube Carcinoma
  • Platinum-Resistant Ovarian Carcinoma
  • Platinum-Resistant Primary Peritoneal Carcinoma
  • Recurrence
  • Recurrent Breast Carcinoma
  • Recurrent High Grade Fallopian Tube Serous Adenocarcinoma
  • Recurrent High Grade Ovarian Serous Adenocarcinoma
  • Recurrent Primary Peritoneal High Grade Serous Adenocarcinoma
  • Recurrent Triple-Negative Breast Carcinoma
  • Refractory Fallopian Tube Serous Adenocarcinoma
  • Refractory Ovarian Serous Adenocarcinoma
  • Refractory Primary Peritoneal Serous Adenocarcinoma
  • Refractory Triple-Negative Breast Carcinoma
  • Triple Negative Breast Neoplasms
  • Unresectable Malignant Solid Neoplasm
  • Unresectable Primary Peritoneal Serous Adenocarcinoma

Intervention

Drug:
Olaparib
Given PO
Onalespib
Given IV

Locations

Country Name City State
United States Beth Israel Deaconess Medical Center Boston Massachusetts
United States Brigham and Women's Hospital Boston Massachusetts
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Massachusetts General Hospital Cancer Center Boston Massachusetts
United States Mayo Clinic in Florida Jacksonville Florida
United States Mayo Clinic Hospital in Arizona Phoenix Arizona
United States Mayo Clinic in Rochester Rochester Minnesota
United States Mayo Clinic in Arizona Scottsdale Arizona

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Maximum Tolerated Dose (MTD) of Olaparib Administered in Combination With Onalespib MTD was determined by testing increasing doses of the combination of olaparib PO and onalespib IV within dose escalation cohorts consisting of 3 to 6 evaluable participants. MTD reflects the highest dose combination that did not cause a Dose-Limiting Toxicity (DLT) in > 33% of participants. DLTs were defined based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Enrollment to this study was suspended prior to completion of the dose escalation due to discontinuation of further development of onalespib. A true single MTD therefore could not be determined. The two dose levels included in this outcome measure represent the highest well-tolerated dose combinations (Dose Level 2 [DL2]: Olaparib 300 mg PO BID and Onalespib 40 mg/m^2 IV; and Dose Level 2a [DL2a]: Olaparib 200 mg PO BID and Onalespib 80 mg/m^2 IV).
Up to 35 days for each dose level cohort
Primary Maximum Tolerated Dose (MTD) of Onalespib Administered in Combination With Olaparib MTD was determined by testing increasing doses of the combination of olaparib PO and onalespib IV within dose escalation cohorts consisting of 3 to 6 evaluable participants. MTD reflects the highest dose combination that did not cause a Dose-Limiting Toxicity (DLT) in > 33% of participants. DLTs were defined based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Up to 35 days for each dose level cohort
Secondary Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) DLTs were based on the NCI Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 and were defined as any grade 3 or 4 non-hematologic toxicity (excluding grade 3: fatigue; diarrhea, constipation, and nausea and/or vomiting controlled with supportive measured within 24 hours; hypophosphatemia; hyponatremia; hypomagnesemia; and rash that resolves to < grade 3 within < 5 days), grade 4 neutropenia of > 7 day duration, febrile neutropenia, grade 4 thrombocytopenia or bleeding associated with grade 3 thrombocytopenia, requirement for repeated blood transfusion within 4-6 weeks, any other grade 4 hematologic toxicity, any study treatment-related death, any grade 3 or 4 event considered to be dose-limiting in the opinion of the investigator, and the inability to take 75% or more of the planned dose for olaparib and 4 out of 6 doses for onalespib within the DLT period due to treatment-related adverse events. Within Cycles 0 and 1 (up to 35 days).
Secondary Number of Participants Who Experienced Treatment-Related Toxicities Treatment-related toxicities in this outcome include non-hematologic and hematologic adverse events that were either Grade 3+ or occurred in at least 10% of all treated participants, and were considered at least possibly related to olaparib and/or onalespib. Adverse events were graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v.5.0. Up to 67 weeks
Secondary Number of Participants With Objective Responses by RECIST 1.1 Responses determined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI, where Objective Response (OR) represents either a Complete Response (CR; disappearance of all target lesions) or a Partial Response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum diameters). Up to 63 weeks
Secondary Number of Participants Progression-Free for At Least 24 Weeks by RECIST 1.1 Responses determined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI, where Progressive Disease (PD) represents (relative to baseline) at least a 20% increase in the sum of diameters of target lesions, appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. The duration of progression-free status was defined as the interval from the date of enrollment to date of either PD or date of last disease assessment. Up to 24 weeks
See also
  Status Clinical Trial Phase
Completed NCT02317874 - Testing the Addition of the Anti-Cancer Drug Talazoparib to the Combination of Carboplatin and Paclitaxel for the Treatment of Advanced Cancer Phase 1
Active, not recruiting NCT04539574 - An Investigational Scan (7T MRI) for the Imaging of Central Nervous System Tumors N/A
Not yet recruiting NCT05095948 - Improving Processes of Cancer Care Delivery at a Comprehensive Cancer Center
Recruiting NCT05691491 - Testing the Combination of the Anti-Cancer Drugs Temozolomide and M1774 to Evaluate Their Safety and Effectiveness Phase 1/Phase 2
Active, not recruiting NCT03218826 - PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery Phase 1
Recruiting NCT05554380 - Study of Chemotherapy Plus Ipatasertib for People With Solid Tumors With AKT Mutations, A ComboMATCH Treatment Trial Phase 2
Recruiting NCT04957615 - Nivolumab for the Treatment of Metastatic or Unresectable Solid Tumors With ARID1A Mutation and CXCL13 Expression Phase 2
Active, not recruiting NCT04294628 - Testing the Biological Effects of DS-8201a on Patients With Advanced Cancer Phase 1
Active, not recruiting NCT03065387 - Neratinib and Everolimus, Palbociclib, or Trametinib in Treating Participants With Refractory and Advanced or Metastatic Solid Tumors With EGFR Mutation/Amplification, HER2 Mutation/Amplification, or HER3/4 Mutation or KRAS Mutation Phase 1
Withdrawn NCT04820894 - Perception of Cure Among Patients With Metastatic Cancer
Completed NCT03229278 - Trigriluzole With Nivolumab and Pembrolizumab in Treating Patients With Metastatic or Unresectable Solid Malignancies or Lymphoma Phase 1
Recruiting NCT02408861 - Nivolumab and Ipilimumab in Treating Patients With HIV Associated Relapsed or Refractory Classical Hodgkin Lymphoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery Phase 1
Active, not recruiting NCT04514497 - Testing the Addition of an Anti-cancer Drug, BAY 1895344, to Usual Chemotherapy for Advanced Stage Solid Tumors, With a Specific Focus on Patients With Small Cell Lung Cancer, Poorly Differentiated Neuroendocrine Cancer, and Pancreatic Cancer Phase 1
Recruiting NCT04673448 - Niraparib and TSR-042 for the Treatment of BRCA-Mutated Unresectable or Metastatic Breast, Pancreas, Ovary, Fallopian Tube, or Primary Peritoneal Cancer Phase 1
Recruiting NCT05638295 - Testing the Use of AMG 510 (Sotorasib) and Panitumumab as a Targeted Treatment for KRAS G12C Mutant Solid Tumor Cancers (A ComboMATCH Treatment Trial) Phase 2
Recruiting NCT05455606 - Does the Use of a Genomic Tumor Board Increase the Number of Patients Who Receive Genome-Informed Treatment N/A
Recruiting NCT05101356 - A Cancer Vaccine (Labvax 3(22)-23) and GM-CSF Alone or in Combination With Pembrolizumab for the Treatment of Advanced Stage Adenocarcinoma Phase 1/Phase 2
Recruiting NCT04960787 - Financial Navigation Program to Improve Understanding and Management of Financial Aspects of Cancer Care for Patients and Their Spouses N/A
Recruiting NCT05803382 - Testing the Addition of an Anti-Cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment (Capecitabine) for Metastatic or Unresectable Cancers Phase 1
Active, not recruiting NCT02143401 - Navitoclax and Sorafenib Tosylate in Treating Patients With Relapsed or Refractory Solid Tumors Phase 1