Trials / Terminated
TerminatedNCT03366103
Navitoclax and Vistusertib in Treating Patients With Relapsed Small Cell Lung Cancer and Other Solid Tumors
Phase 1/2 Study of Navitoclax Plus Vistusertib in Patients With Relapsed Small Cell Lung Cancer (SCLC) and Other Solid Tumors
- Status
- Terminated
- Phase
- Phase 1 / Phase 2
- Study type
- Interventional
- Enrollment
- 15 (actual)
- Sponsor
- National Cancer Institute (NCI) · NIH
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
Summary
This phase I/II trial studies the best dose and side effects of navitoclax and how well it works when given together with vistusertib in treating patients with small cell lung cancer and solid tumors that have come back (relapsed). Drugs used in chemotherapy, such as navitoclax, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Vistusertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving navitoclax and vistusertib may work better than navitoclax alone in treating patients with small cell lung cancer and solid tumors.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of the combination of navitoclax and vistusertib in patients with advanced solid tumors. (Phase I) II. To determine the maximum tolerated dose (MTD), dose limiting toxicities (DLT), and recommended phase 2 doses (RP2D) of navitoclax and vistusertib. (Phase I) III. To determine the objective response rate (ORR), defined as complete plus partial response, of the combination of navitoclax and vistusertib in patients with recurrent small cell lung cancer (SCLC). (Phase II) SECONDARY OBJECTIVES: I. To evaluate the pharmacokinetics of navitoclax and vistusertib when administered together. (Phase I) II. To observe and record anti-tumor activity. (Phase I) III. To confirm the safety and tolerability of navitoclax and vistusertib at the RP2D. (Phase II) IV. To estimate progression free survival (PFS) and overall survival (OS) of the combination of navitoclax and vistusertib at the RP2D. (Phase II) V. To estimate disease control rate (DCR) of the combination of navitoclax and vistusertib at the RP2D. (Phase II) CORRELATIVE OBJECTIVES: I. To assess pharmacodynamic changes in levels of phosphorylated 4EBP1 (p4EBP1) the ratio of p4EBP1 to total (p4EBP1/4EBP1) in paired pre-treatment and on-treatment biopsies at the RP2D. (Phase II) II. To correlate changes in BAX and MCL-1 with response. (Phase II) III. To estimate the baseline inter-patient variability in p4EBP1, pS6, BAX, and MCL-1. (Phase II) IV. To explore exposure-response relationships between navitoclax and vistusertib exposure and the pharmacodynamic endpoints (safety, efficacy, and laboratory correlatives). (Phase II) OUTLINE: This is a phase I, dose-escalation study followed by a phase II study. Patients receive navitoclax orally (PO) once daily (QD) and vistusertib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days and then every 8-12 weeks for up to 2 years.
Conditions
- Metastatic Malignant Solid Neoplasm
- Recurrent Lung Small Cell Carcinoma
- Recurrent Malignant Solid Neoplasm
- Refractory Malignant Solid Neoplasm
- Stage III Lung Small Cell Carcinoma, by American Joint Committee on Cancer (AJCC) v7
- Stage IIIA Lung Small Cell Carcinoma AJCC v7
- Stage IIIB Lung Small Cell Carcinoma AJCC v7
- Stage IV Lung Small Cell Carcinoma AJCC v7
- Unresectable Solid Neoplasm
Interventions
| Type | Name | Description |
|---|---|---|
| BIOLOGICAL | Navitoclax | Given PO |
| DRUG | Vistusertib | Given PO |
Timeline
- Start date
- 2018-03-20
- Primary completion
- 2021-07-28
- Completion
- 2022-09-21
- First posted
- 2017-12-08
- Last updated
- 2023-10-17
- Results posted
- 2023-05-03
Locations
14 sites across 1 country: United States
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT03366103. Inclusion in this directory is not an endorsement.