Phase II Trial of Pembrolizumab and Lenvatinib for Leptomeningeal Metastases
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Solid Tumor
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 10
- Locations
- 2
- Primary Endpoint
- Proportion of Participants alive at 6 months
- Status
- Terminated
- Last Updated
- 9 months ago
Overview
Brief Summary
The purpose of this research is to examine if an experimental drug combination impacts the survival rate of individuals with Leptomeningeal Metastases
This research study involves an experimental drug combination.
The names of the study drugs involved in this study are:
- Pembrolizumab
- Lenvatinib
Detailed Description
This is a single arm Phase 2 study of pembrolizumab in combination with lenvatinib in patients with leptomeningeal metastases from any solid tumor. The research study procedures include screening for eligibility and study treatment, including evaluations and follow up visits. * The names of the study drugs involved in this study are: * Pembrolizumab * Lenvatinib The study treatment will last for up to 35 cycles (a cycle is 21 days long), or until the disease gets worse or unacceptable side effects. Participants will be followed for up to 90 days after the end of the study treatment. It is expected that about 19 people will take part in this research study. This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug combination to learn whether the drug combination works in treating a specific disease. "Investigational" means that the drug combination is being studied. The U.S. Food and Drug Administration (FDA) has not approved pembrolizumab or lenvatinib for this specific disease but each has been approved for other uses. . .
Investigators
Nancy Wang, M.D.
Principal Investigator
Massachusetts General Hospital
Eligibility Criteria
Inclusion Criteria
- •Participants must have histologically or cytologically confirmed solid malignancy.
- •Leptomeningeal metastases, as determined by: 1) positive CSF cytology, or 2) MRI suggestive of leptomeningeal metastases and atypical cytology.
- •Age ≥18 years. Because no dosing or adverse event data are currently available on the use of pembrolizumab in combination with lenvatinib in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
- •ECOG performance status ≤ 1 (Karnofsky ≥70%, see Appendix A)
- •Participants must have normal organ and marrow function; all screening labs should be performed within 14 days of treatment initiation.
- •Eligibility Criteria for Organ and Marrow Function
- •Hematological
- •Absolute neutrophil count (ANC) ≥1500/μL
- •Platelets ≥100 000/μL
- •Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La
Exclusion Criteria
- •Participants who have received prior systemic anti-cancer therapy including investigational agents within 14 days of protocol treatment. Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
- •Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- •Participant must have recovered adequately from the toxicity and/or complications from any prior surgical procedures prior to starting therapy. Lenvatinib should be held for 4 weeks following a major surgical procedure, 2 weeks following a minor surgical procedure.
- •Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- •HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pembrolizumab. In addition, these participants are at increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated. No testing for HIV, Hepatitis B, and Hepatitis C is required unless mandated by local health authority.
- •Participants who are receiving any other investigational agents.
- •Has a diagnosis of immunodeficiency.
- •Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
Arms & Interventions
PEMBROLIZUMAB and LENVATINIB
The research study procedures include screening for eligibility and study treatment, including evaluations and follow up visits. * PEMBROLIZUMAB daily, every 3 weeks * LENVATINIB daily every 3 weeks
Intervention: Pembrolizumab
PEMBROLIZUMAB and LENVATINIB
The research study procedures include screening for eligibility and study treatment, including evaluations and follow up visits. * PEMBROLIZUMAB daily, every 3 weeks * LENVATINIB daily every 3 weeks
Intervention: Lenvatinib
Outcomes
Primary Outcomes
Proportion of Participants alive at 6 months
Time Frame: 6 months
The proportion of patients alive at 6 months will be summarized with a 90% confidence interval estimated using the method of Atkinson and Brown (Biometrics, 1985), which allows for the two-stage design. Based on a sample of 19 patients, the confidence interval will be no wider than 33%
Secondary Outcomes
- Intracranial/intraspinal Progression Free Survival (IPFS)(30 Months)
- Median Intracranial/intraspinal Progression Free Survival (IPFS)(30 Months)
- Median Overall Survival(30 Months)
- Proportion of participants with leptomeningeal metastases from breast cancer alive(6 months)
- Proportion of evaluable participants with intracranial/intraspinal response(30 Months)
- Proportion of evaluable participants with extracranial response(30 Months)
- Proportion of Participants with Grade 3 or higher toxicities(first dose of study treatment up to the 30-Day Post Drug Visit up to 30 Months)
- Median Extracranial Progression Free Survival (EPFS)(30 Months)
- Overall Survival(30 Months)
- Extracranial Progression Free Survival (EPFS)(30 Months)