Phase 1
Completed N=3
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
Metastatic High Grade Fallopian Tube Serous Adenocarcinoma · Metastatic Malignant Solid Neoplasm · Metastatic Primary Peritoneal Serous Adenocarcinoma · Metastatic Triple-Negative Breast Carcinoma
Source: ClinicalTrials.gov NCT02898207 ↗
Enrolled (actual)
3
Serious AEs
42.9%
Results posted
Apr 2023
Primary outcomePrimary: Maximum Tolerated Dose (MTD) of Olaparib Administered in Combination With Onalespib — 300; 200 mg
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) of Olaparib Administered in Combination With Onalespib |
300; 200 | — |
| PRIMARY Maximum Tolerated Dose (MTD) of Onalespib Administered in Combination With Olaparib |
40; 80 | — |
| SECONDARY Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) |
0; 0; 0; 0; 2; 1 | — |
| SECONDARY Number of Participants Who Experienced Treatment-Related Toxicities |
3; 3; 3; 5; 3; 4 | — |
| SECONDARY Number of Participants With Objective Responses by RECIST 1.1 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants Progression-Free for At Least 24 Weeks by RECIST 1.1 |
1; 2; 1; 1; 1; 1 | — |
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 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 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]) = = 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 par
Data sourced from ClinicalTrials.gov (NCT02898207). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.