Neoadjuvant Immunotherapy in Brain Metastases

NCT04434560 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: Pro00103812CA184-583
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this phase 2 study is to assess the feasibility and efficacy of neoadjuvant immunotherapy in patients with previously untreated, surgically-resectable, solid tumor brain metastases. The primary objectives of this study are to 1) assess the feasibility of neoadjuvant ipilimumab and nivolumab treatment before surgery and stereotactic radiosurgery (SRS) in patients with solid tumor brain metastases as measured by the proportion of patients who have their surgery delayed or surgery never occurs, and 2) demonstrate that neoadjuvant immunotherapy will increase proliferation of circulating T-cells compared to baseline measurements. Exploratory objectives include describing patient progression free survival and overall survival, time to local and distant intracranial progression, and the rate of radiation necrosis. The rate of radionecrosis will also be explored, as immune expression profiles.

Conditions

Brain Metastases, Adult

Keywords

Pro00103812; Sammons; Non-small-cell lung carcinoma; Renal cell carcinoma; Urothelial carcinoma; Melanoma; Ovarian carcinoma; Triple negative breast cancer; Solid tumor; Brain metastases; Nivolumab; Ipilimumab; Opdivo; Yervoy

Outcome Measures

Primary Outcomes (2)

• Proportion of Patients Who Have Their Surgery Delayed by More Than 4 Days or Surgery Never Occurs as a Direct or Indirect Result of Ipilimumab and Nivolumab Treatment.

  10 days

• Proliferation of Circulating T-cells as Measured by Mean Fold-change Between Baseline and Day 1 in Ki67 Levels.

  Ki-67 is a nuclear protein involved in cell proliferation regulation.

  baseline to day 1

Study Arms (2)

Standard of Care (no neoadjuvant immunotherapy)

NO INTERVENTION

Patients will proceed to surgical resection with no nivolumab/ipilimumab given prior to surgery.

Neoadjuvant Immunotherapy

EXPERIMENTAL

Patients will receive a single dose of neoadjuvant nivolumab and ipilimumab 7 days (± 3 days) prior to surgical resection.

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

Nivolumab will be given at the FDA-approved dose of 3 mg/kg.

Also known as: Opdivo

Neoadjuvant Immunotherapy

Ipilimumab DRUG

Ipilimumab will be given at the FDA-approved dose of 1 mg/kg.

Also known as: Yervoy

Neoadjuvant Immunotherapy

Eligibility Criteria

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

You may qualify if:

• \. Patients must have at least 1 previously untreated, solid tumor brain metastases that are ≤4 cm in the largest direction. At least one of the metastases must be surgically resectable. All metastases must be planned for treatment with SRS. Primary tumor histology must be one of the following:
• Squamous NSCLC
• Non-squamous NSCLC without known ALK, EGFR, and ROS mutation
• RCC
• Urothelial carcinoma
• Ovarian carcinoma
• Melanoma
• Triple negative breast cancer that is PD-L1 positive
• Other solid tumor histologies may be eligible at the discretion of the PI if they are known to respond to immunotherapy containing regimens.
• \. Patient must be asymptomatic or minimally symptomatic, requiring the equivalent of ≤ 4 mg dexamethasone daily for at least 7 days prior to enrollment
• \. Patient or partner(s) meets one of the following criteria:
• Non-childbearing potential (i.e. not sexually active, physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile, or any male who has had a vasectomy). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Postmenopausal for purposes of this study is defined as 1 year without menses.; or
• Childbearing potential and agrees to use one of the following methods of birth control: approved hormonal contraceptives (e.g. birth control pills, patches, implants, or infusions), an intrauterine device, or a barrier method of contraception (e.g. a condom or diaphragm) used with spermicide.
• \. Age ≥ 18 years of age at the time of entry into the study
• \. Karnofsky Performance Score (KPS) ≥ 70

You may not qualify if:

• \. Females who are pregnant or breast-feeding
• \. Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons or their designate
• \. Patients with severe, active co-morbidity, defined as follow:
• Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax \> 99.5°F/37.5°C)
• Patients with known immunosuppressive disease or known uncontrolled human immunodeficiency virus infection
• Patients with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4)
• \. Patients who have not recovered from the toxic effects of prior chemo- and/or radiation therapy. Guidelines for this recovery period are dependent upon the specific therapeutic agent being used:
• \. Patients must not have received immunotherapy within 3 months prior to enrollment
• \. Patients with prior, unrelated malignancy requiring current active treatment in the last 3 years with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
• \. Patients with a known history of hypersensitivity to nivolumab, or any components of nivolumab
• \. Patients with a known history of hypersensitivity to ipilimumab, or any components of ipilimumab
• \. Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months.
• \. History and/or confirmed pneumonitis, or extensive bilateral lung disease on high resolution/spiral CT scan.

Sponsors & Collaborators

• Sarah Sammons, MD: lead
• Bristol-Myers Squibb: collaborator
• Duke University: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center
• Duke Health

MeSH Terms

Conditions

Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Melanoma; Ovarian Neoplasms; Triple Negative Breast Neoplasms

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Neoplasms; Breast Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Sarah Sammons, MD
• Organization: Duke University

sarah.sammons@duke.edu

919-684-4563

Study Officials

• Sarah Sammons, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: June 12, 2020
• First Posted: June 17, 2020
• Study Start: November 4, 2020
• Primary Completion: June 17, 2021
• Study Completion: June 17, 2021
• Last Updated: July 26, 2022
• Results First Posted: July 26, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)