Recruitment

Recruitment Status
Recruiting
Estimated Enrollment
75

Summary

Conditions
  • Lung Neoplasms
  • Prostate Cancer
  • Small Cell Lung Cancer
  • Urothelial Cancer
  • Urothelial Carcinoma
Type
Interventional
Phase
Phase 1Phase 2
Design
Allocation: Non-RandomizedIntervention Model: Sequential AssignmentMasking: None (Open Label)Primary Purpose: Treatment

Participation Requirements

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

Description

Background: Small cell lung cancer (SCLC) is an aggressive cancer with a poor prognosis. Although highly responsive to chemotherapy initially, SCLC relapses quickly and becomes refractory to treatment within a few months. Urothelial Carcinoma (UC) of the Bladder is the fourth most common malignancy ...

Background: Small cell lung cancer (SCLC) is an aggressive cancer with a poor prognosis. Although highly responsive to chemotherapy initially, SCLC relapses quickly and becomes refractory to treatment within a few months. Urothelial Carcinoma (UC) of the Bladder is the fourth most common malignancy in men and the ninth most common in women. Prostate cancer is the most common cancer among men in the United States. While prostate cancer is initially responsive to androgen deprivation therapy (ADT), the median duration of sensitivity is 24-36 months. Moreover, patients develop resistance to current treatment options. The use of PARP inhibitors in combination with chemotherapy builds upon pre-clinical data in lung cancer and other cancers supporting the notion that PARP inhibitors potentiate the effect of DNA damaging therapies. Despite their highly synergistic activity in preclinical models, human studies combining PARP inhibitors and camptothecins have not translated into clinical benefit due to enhanced toxicity with the combination. One approach to improve ability to combine camptothecins with agents that sensitize their activity like PARP inhibitors is to use alternative formulations that minimize toxicity to the normal tissues. EP0057 is a nanoparticle drug conjugate composed of 20 (S)-camptothecin (a potent and highly selective topoisomerase I inhibitor) conjugated to a linear, cyclodextrinpolyethylene glycol-based polymer. Olaparib is a PARP inhibitor indicated as monotherapy in patients with deleterious or suspected deleterious germline BRCA mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Olaparib has an established safety profile and it is under investigation in a number of different cancers. Objectives: Phase I: To determine the MTD/ recommended Phase 2 dose (RP2D) of EP0057 in combination with olaparib in patients with refractory cancers Phase II: To determine the antitumor activity of olaparib plus EP0057 with respect to progression free survival at 16 weeks in SCLC patients with resistant or sensitive relapse Expansion Cohorts: To determine overall response rate of EP0057 plus olaparib in patients with mCRPC and urothelial carcinoma Eligibility: Phase I: Male or female adult patients greater than or equal to 18 years of age Histologically or cytologically confirmed, advanced solid tumor that is refractory to standard therapy and/or for whom no further standard therapy is available -ECOG Performance Status of 0, 1 or 2 Phase II: Male or female patients greater than or equal to 18 years old Have a pathologically (histology or cytology) confirmed diagnosis of SCLC Disease progression on or after at least one platinum-based standard chemotherapy regimen and/or an immune-checkpoint inhibitor for either limited or extensive stage disease. Have measurable disease per RECIST 1.1 ECOG performance status of 0, 1 or 2 Phase II Expansion Cohorts: -Have a pathologically (histology or cytology) confirmed diagnosis of urothelial carcinoma or metastatic, progressive, castrate resistant prostate cancer (mCRPC) -Disease progression on or after at least one platinum-based standard chemotherapy regimen and/or an immune-checkpoint inhibitor (except prostate cohort) Have measurable disease per RECIST 1.1 (except prostate cohort) Prior treatment with enzalutamide and/or abiraterone (prostate cancer cohort only) Patients must have castrate levels of testosterone (<50 ng/dl [1.74 nmol/l]) (Prostate cohort only) Design: Patients meeting eligibility criteria will receive EP0057 (IV Q 2weeks) plus olaparib (PO BID days 3-13 and days 17-26 administered in 28 day cycles, until disease progression or development of intolerable side effects. The MTD of the combination will be used in Phase II. Patients in Phase II will receive, the RP2D at DL4R EP005712mg/m2 and olaparib 250mg BID. Blood, tumor and hair samples will be collected at multiple time points for PK, PD analyses. Hair sample collection is optional. Tumor biopsies are optional for SCLC and UC patients and mandatory for mCRPC patients (only baseline biopsy is mandatory). Toxicity will be graded according to CTCAE version 4.0. Tumor assessments will be made using CT scans (chest, abdomen and pelvis) at baseline and after every 2 cycles (3 cycles for mCRPC) according to RECIST version 1.1. After discontinuation of study treatment, follow-up for survival will be carried out every 3 months. The maximum number of patients on the phase I portion of the trial is 30, the SCLC cohort in phase II may accrue up to 27 evaluable patients, urothelial carcinoma expansion cohort may accrue up to 34 patients and mCRPC may accrue up to 25 patients. Thus, the maximum number of evaluable patients who may enroll on this trial is 116. In order to allow for a small number of in-evaluable patients, the accrual ceiling will be set at 123. It is anticipated that approximately 1 to 2 patients per month may enroll onto this trial; the trial is expect to complete accrual in 6-8 years.

Tracking Information

NCT #
NCT02769962
Collaborators
Not Provided
Investigators
Principal Investigator: Anish Thomas, M.D. National Cancer Institute (NCI)