Phase I/Ib Study of Concurrent Intravenous and Intrathecal Nivolumab for Melanoma and Lung Cancer Patients With Leptomeningeal Disease (LMD)

NCT: NCT03025256 · Status: RECRUITING · Phase: Phase 1 · Sponsor: M.D. Anderson Cancer Center · Started: 2018-05-02 · Est. Completion: 2027-06-01

Official Summary

This phase I/Ib trial studies the side effects and best dose of intrathecal nivolumab, and how well it works in combination with intravenous nivolumab in treating patients with leptomeningeal disease. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Study Design

Interventions

Primary Outcomes

Secondary Outcomes

Eligibility Criteria

Inclusion Criteria:

* Patients must have radiographic and/or CSF cytological evidence of LMD. For patient with melanoma: Must have a confirmed diagnosis of primary central nervous system (CNS) melanoma, melanocytomas or metastatic melanoma (cutaneous, acral-lentiginous, uveal and mucosal in origin), based on histological analysis of metastatic tissue and/or cancer cells, archival tissue permitted. For patients with lung cancer: non-small cell, based on histological analysis of metastatic tissue and/or cancer cells, archival tissue permitted
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of =\< 2
* Patients may receive steroids to control symptoms related to CNS involvement, but the dose must be =\< 4 mg per 24 hours of dexamethasone (or the equivalent). Physiologic replacement doses for adrenal insufficiency is allowed on this protocol
* Patients who have received radiation to brain and/or spine, including whole brain radiation, stereotactic radiosurgery, or stereotactic body radiation therapy (SBRT), are eligible, but must have completed radiation treatment at least 7 days prior to the start of treatment
* Patients who have been treated with an approved targeted therapy (BRAF inhibitor and/or MEK inhibitor) will be allowed to remain on concurrent approved targeted therapy. No other concomitant intrathecal therapy with another agent will be allowed. For patients that have received other systemic therapies, the minimum wash out period is as follows:

  * Patients that received previous IT therapy must have received their last treatment \>= 7 days prior to the start of treatment
  * Patients who have received systemic chemotherapy must have received their last treatment \>= 14 days prior to the start of treatment
  * Patients who have received an approved systemic biologic therapy (e.g. anti-PD-1, anti-CTLA4, IL2, interferon) must have received their last treatment \>= 2 weeks prior to the start of treatment
  * Patients who have received any other investigational agents must have received their last treatment \>= 14 days prior to the start of treatment
* For patients with lung cancer:

  * For chemotherapy: patients do not require a washout period, and can continue with chemotherapy during treatment with IT/IV nivolumab
  * Patients who have received an approved systemic biologic therapy (e.g. anti-PD-1, anti-CTLA4, IL2, interferon) must have received their last treatment \>= 2 weeks prior to the start of treatment
  * Patients who have received any other investigational agents must have received their last treatment \>= 14 days prior to the start of treatment
  * No other concomitant intrathecal therapy with another agent will be allowed
  * Patients who are receiving treatment to tyrosine kinase inhibitors or other targeted therapy agents do not require a washout period, and can continue with tyrosine kinase inhibitors or other targeted therapy agents during treatment with IT/IV nivolumab
* Age \>= 18 years
* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
* Absolute neutrophil count (ANC) \>= 1.5 X 10\^9/L
* Hemoglobin \>= 9.0 g/dL
* Platelets \>= 75 X 10\^9/L
* Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =\< 1.5 X upper limit of normal (ULN)
* Total bilirubin: =\< 1.5 X ULN (isolated bilirubin \> 1.5 X ULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35%)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 X ULN
* Albumin \>= 2.5 g/dL
* Creatinine OR =\< 2 x ULN; calculated creatinine clearance OR \>= 50 mL/min; 24-hour urine creatinine clearance \>= 50 mL/min
* Absence of contraindication for Ommaya reservoir
* Women are eligible to participate if:

  * Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/mL and estradiol \< 40 pg/mL (\<140 pmol/L) is confirmatory\]
  * A Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level \> 40mIU/mL to confirm menopause
  * Females treated with hormone replacement therapy, (HRT) are likely to have artificially suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH level. The duration of the washout period is a function of the type of HRT used. The duration of the washout period below are

Trial Locations

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AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.