Navitoclax and Vistusertib in Treating Patients With Relapsed Small Cell Lung Cancer and Other Solid Tumors

NCT03366103 | Terminated Phase 1 Results DMC FDA Drug

• 4 other identifiers: NCI-2017-00037ETCTN1007010070UM1CA186691
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 14

Brief 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.

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicities (Phase I)

  Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0. The number of participants with dose limiting toxicities at each dose level will be reported with exact binomial 95% confidence intervals. All patients who receive at least 1 dose of both study drugs, regardless of their eligibility for the study, will be evaluable for toxicity.

  Up to 30 days after last treatment, an average of 3 months

• Overall Response Rate (ORR) (Phase II)

  Defined as Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. partial response or complete response, of the combination in patients with recurrent small cell lung cancer. The ORR will be reported with its corresponding 95% confidence interval.

  Up to 1.5 years

Secondary Outcomes (5)

• Occurrence of a Bi-directional Pharmacokinetic (PK) Interaction

  Through Day 15

• Number of Participants Experiencing Adverse Events by Grade (Phase II)

  Up to 1.5 years

• Progression Free Survival (PFS) (Phase II)

  Up to 1.5 years

• Overall Survival (OS) at Year 1 (Phase II)

  At Year 1

• Disease Control Rate (Phase II)

  Up to 1.5 years

Other Outcomes (5)

• Change in p4EBP1 Expression

  Baseline up to 1.5 years

• Change in Ratio p4EBP1/4EBP1

  Baseline up to 1.5 years

• Change in Ratio pS6/S6

  Baseline up to 1.5 years

Study Arms (1)

Treatment (navitoclax, vistusertib)

EXPERIMENTAL

Patients receive navitoclax PO QD and vistusertib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Navitoclax; Drug: Vistusertib

Interventions

Navitoclax BIOLOGICAL

Given PO

Also known as: A-855071.0, ABT-263, BcI-2 Family Protein Inhibitor ABT-263

Treatment (navitoclax, vistusertib)

Vistusertib DRUG

Given PO

Also known as: AZD 2014, AZD-2014, AZD2014

Treatment (navitoclax, vistusertib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PHASE 1 SPECIFIC ELIGIBILITY CRITERIA
• 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
• PHASE 2 SPECIFIC ELIGIBILITY CRITERIA
• Patients must have histologically or cytologically confirmed small cell lung cancer whose disease has relapsed or progressed after \>= 1 prior therapy, one of which must have been a platinum doublet; pathology confirmation must be done at Sidney Kimmel Comprehensive Cancer Center (SKCCC) or at the local participating site
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) by chest x-ray or as \>= 10 mm (\>= 1 cm) with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Subjects must be willing to undergo 2 sets of core needle biopsies (pre-treatment and on-treatment), if there are lesions amenable to biopsy; an optional core biopsy will be requested at progression
• GENERAL ELIGIBILITY CRITERIA
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
• Life expectancy of greater than 12 weeks
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Hemoglobin \>= 9.0 g/dL
• Platelets \>= 100,000/mcL
• Activated partial thromboplastin time (aPTT), prothrombin time (PT) =\< 1.2 x upper limit of normal (ULN)
• Total bilirubin =\< 1.5 x ULN (patients with Gilbert's syndrome may have serum bilirubin \> 1.5 ULN)

You may not qualify if:

• Prior treatment with a TORC1, dual TORC1/2 inhibitor, or BCL-2/xL inhibitor
• Patients with active malignancies other than SCLC or patients with prior curatively treated malignancy at high risk of relapse during the study period with the exception of localized squamous or basal cell skin cancers
• Major surgery within 21 days of starting protocol treatment
• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to navitoclax or vistusertib
• Patients receiving anticoagulation or anti-platelet therapy are excluded due to the risk of thrombocytopenia with navitoclax
• Excluded agents include heparin or low molecular weight heparin, warfarin, clopidogrel, ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDS), tirofiban, and other anticoagulants, drugs, or herbal supplements that affect platelet function
• Administration of heparin to keep subject's infusion lines patent is allowed; low-dose anticoagulation medications that are used to maintain the patency of a central intravenous catheter are allowed
• Aspirin will not be allowed within 7 days prior to the first dose of navitoclax or during navitoclax administration; however, subjects who have previously received aspirin therapy for thrombosis prevention, may resume a low dose (i.e., maximum 100 mg once daily \[QD\]) of aspirin if platelet counts are stable (\>= 50,000/mm3) through 6 weeks of navitoclax administration
• All decisions regarding treatment with aspirin therapy will be determined by the investigator in conjunction with the medical monitor
• Patients with an underlying condition predisposing them to bleeding or currently exhibiting signs of clinically significant bleeding
• Patients with a recent history of non-chemotherapy-induced thrombocytopenic-associated bleeding within 1 year prior to the first dose of study drug
• Patients with a significant history of cardiovascular disease or procedures within the preceding 6 months (e.g., myocardial infarction \[MI\], coronary artery bypass graft placement, angioplasty, vascular stent, angina pectoris, ventricular arrhythmias requiring continuous therapy, congestive heart failure New York Heart Association \[NYHA\] grade \>= 2, thrombotic or thromboembolic event)
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc using Fridericia's formula \[QTcF\]) \> 470 msec obtained from 3 electrocardiograms

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (14)

Los Angeles County-USC Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Publications (1)

• Scott SC, Farago A, Lai WV, Zahurak M, Rudek MA, Murray J, Carducci MA, Uziel T, Takebe N, Gore SD, Rudin CM, Hann CL. A phase 1 study of the combination of BH3-mimetic, navitoclax, and mTORC1/2 inhibitor, vistusertib, in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2025 Feb 25;95(1):37. doi: 10.1007/s00280-025-04760-1.

  PMID: 39998620 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Small Cell Lung Carcinoma

Interventions

navitoclax; vistusertib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Only 1 participant was enrolled to Phase 2 before the study was closed to accrual for low accrual.

Results Point of Contact

• Title: Judy Murray
• Organization: Johns Hopkins University/SKCCC

jmurra33@jhmi.edu

443-927-3568

Study Officials

• Christine L Hann

  JHU Sidney Kimmel Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2017
• First Posted: December 8, 2017
• Study Start: March 20, 2018
• Primary Completion: July 28, 2021
• Study Completion: September 21, 2022
• Last Updated: October 17, 2023
• Results First Posted: May 3, 2023

Record last verified: 2023-09

Locations

US (14)