Recruitment

Recruitment Status
Active, not recruiting
Estimated Enrollment
60

Summary

Conditions
  • Metastatic Primary Peritoneal Serous Adenocarcinoma
  • Metastatic Fallopian Tube Serous Adenocarcinoma
  • Metastatic Malignant Solid Neoplasm
  • Refractory Primary Peritoneal Serous Adenocarcinoma
  • Refractory Triple-Negative Breast Carcinoma
  • Metastatic Triple-Negative Breast Carcinoma
  • Refractory Ovarian Serous Adenocarcinoma
  • Platinum-Resistant Fallopian Tube Carcinoma
  • Platinum-Resistant Ovarian Carcinoma
  • Platinum-Resistant Primary Peritoneal Carcinoma
  • Unresectable Fallopian Tube Serous Adenocarcinoma
  • Unresectable Malignant Solid Neoplasm
  • Recurrent Triple-Negative Breast Carcinoma
  • Unresectable Primary Peritoneal Serous Adenocarcinoma
  • Recurrent Breast Carcinoma
  • Recurrent High Grade Fallopian Tube Serous Adenocarcinoma
  • Recurrent High Grade Ovarian Serous Adenocarcinoma
  • Recurrent Primary Peritoneal High Grade Serous Adenocarcinoma
  • Refractory Fallopian Tube Serous Adenocarcinoma
Type
Interventional
Phase
Phase 1
Design
Allocation: N/AIntervention Model: Single Group AssignmentMasking: None (Open Label)Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

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...

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. EXPLORATORY OBJECTIVES: I. To test the hypothesis that there will be induction of BRCA1 and RAD51 foci after olaparib alone and reduced formation of these foci after the combination of AT13387 and olaparib, assessed immunohistochemically. II. To assess downregulation of expression of HR pathway genes after the combination of AT13387 and olaparib. III. To assess whether there is induction of BRCA1 and RAD51 foci after olaparib alone assessed immunohistochemically in the optional biopsy performed after olaparib alone compared to the optional baseline biopsy prior to initiation of the study. IV. To assess whether there is reduction of BRCA1 and RAD51 foci after the combination of olaparib and AT13387 assessed immunohistochemically in the optional biopsy performed after one of the combination olaparib and AT13387 doses (compared to the optional biopsy after olaparib alone). V. To assess whether there is induction of HSP70 (a known biomarker of HSP90 inhibition) after the combination of olaparib and AT13387 assessed immunohistochemically in the optional biopsy performed after one of the combination olaparib and AT13387 doses (compared to the optional biopsy after olaparib alone). VI. To assess whether there is downregulation of expression of HR pathway genes after the combination of AT13387 and olaparib assessed by Nanostring in the optional biopsy performed after one of the combination olaparib and AT13387 doses (compared to the optional biopsy after olaparib alone). VII. To assess whether there is induction of phosphorylation (phospho) H2AX after the combination of AT13387 and olaparib assessed by immunohistochemistry in the optional biopsy performed. VIII. To assess whether there is downregulation of CCNE1 after the combination of AT13387 and olaparib assessed by immunohistochemistry in the optional biopsy performed. 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.

Tracking Information

NCT #
NCT02898207
Collaborators
Not Provided
Investigators
Principal Investigator: Panagiotis A Konstantinopoulos Dana-Farber - Harvard Cancer Center LAO