A Phase II Trial of PD-L1 Therapy Combined With Anti-VEGF Therapy in Unresectable or Metastatic Melanoma
Overview
- Phase
- Phase 2
- Intervention
- Atezolizumab
- Conditions
- Not specified
- Sponsor
- Elizabeth Buchbinder, MD
- Enrollment
- 30
- Locations
- 3
- Primary Endpoint
- Overall Response Rate in PD-L1 negative melanoma
- Status
- Active, not recruiting
- Last Updated
- 10 months ago
Overview
Brief Summary
This research study is studying a combination of two drugs that change the immune system and tumor as a possible treatment for metastatic or unresectable stage III or IV cutaneous melanoma.
The names of the study drugs involved in this study are:
- Atezolizumab
- Bevacizumab
Detailed Description
The research study procedures include screening for eligibility, study treatment including evaluations, a biopsy, and follow up visits. This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied. The U.S. Food and Drug Administration (FDA) has not approved atezolizumab for this specific disease but it has been approved for other uses. The U.S. Food and Drug Administration (FDA) has not approved bevacizumab for this specific disease but it has been approved for other uses. Atezolizumab and bevacizumab are types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells and stop the growth of cancer. Atezolizumab and bevacizumab work by stopping various molecules on cancer cells and body cells from working against the immune system's natural fight against cancer.
Investigators
Elizabeth Buchbinder, MD
Sponsor Investigator
Dana-Farber Cancer Institute
Eligibility Criteria
Inclusion Criteria
- •Participants must have histologically or cytologically confirmed metastatic or unresectable stage III or IV cutaneous melanoma.
- •PD-L1 negative staining in at least one biopsy sample.
- •Age ≥ 18 years
- •ECOG performance status ≤ 2 (Karnofsky ≥60%, see Appendix A)
- •Participants may have received any number of prior therapies for treatment of their cutaneous melanoma, excluding prior treatment with anti-PD-L1 therapeutic antibodies or bevacizumab.
- •Participants must have measurable disease per RECIST v1.
- •Participants must have availability of a representative tumor specimen for exploratory biomarker research.
- •Participants must have normal organ and marrow function as defined below:
- •lymphocyte count ≥ 500/mcL
- •absolute neutrophil count ≥ 1,500/mcL without granulocyte colony-stimulating factor support
Exclusion Criteria
- •Participants with symptomatic, untreated, or actively progressing CNS metastases will be excluded. If a participant has a known history of treated CNS lesions, they are eligible provided that all of the following criteria are met:
- •Measurable disease, per RECIST v1.1, must be present outside the CNS.
- •The participant has no history of intracranial hemorrhage or spinal cord hemorrhage.
- •Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla, or spinal cord).
- •There is no evidence of interim progression between completion of CNS-directed therapy and the screening brain scan
- •The participant has not received stereotactic radiotherapy within 7 days prior to initiation of study treatment or whole-brain radiotherapy within 14 days prior to initiation of study treatment.
- •The participant has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted. Asymptomatic patients with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery, with no need to repeat the screening brain scan.
- •History of leptomeningeal disease.
- •Uncontrolled tumor-related pain.
- •NOTE: Participants requiring pain medication must be on a stable regimen at study entry.
Arms & Interventions
Atezolizumab and Bevacizumab
The research study procedures include screening for eligibility, study treatment including evaluations, a biopsy, and follow up visits. * Atezolizumab will be administered intravenously at a fixed predetermined dose every three weeks * Bevacizumab will be administered intravenously at a fixed predetermined dose every three weeks, with 21 consecutive days defined as a treatment cycle. Treatment will be administered on an outpatient basis Study treatment will continue until study doctors decide to stop therapy due to criteria which may include disease progression, adverse events or changes in condition. Participants will be followed for survival health information following treatment until the study ends, which could be approximately 5 years from start of treatment
Intervention: Atezolizumab
Atezolizumab and Bevacizumab
The research study procedures include screening for eligibility, study treatment including evaluations, a biopsy, and follow up visits. * Atezolizumab will be administered intravenously at a fixed predetermined dose every three weeks * Bevacizumab will be administered intravenously at a fixed predetermined dose every three weeks, with 21 consecutive days defined as a treatment cycle. Treatment will be administered on an outpatient basis Study treatment will continue until study doctors decide to stop therapy due to criteria which may include disease progression, adverse events or changes in condition. Participants will be followed for survival health information following treatment until the study ends, which could be approximately 5 years from start of treatment
Intervention: Bevacizumab
Outcomes
Primary Outcomes
Overall Response Rate in PD-L1 negative melanoma
Time Frame: 5 Years
The primary endpoint for this study is overall response rate in PDL1 negative melanoma to combination anti-PD-L1 therapy and anti-VEGF therapy by RECIST criteria. The proportion of patients with complete response or partial response as best response to therapy will be summarized and presented with a two-sided, 90% Wald confidence interval.
Secondary Outcomes
- Time to tumor progression(up to 5 years)
- Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE 5.(initiation of study treatment, during study treatment, and 30 days after the last dose of study treatment or study discontinuation/termination, whichever occurs first up to 5 years)
- Overall survival(start of treatment and death from any cause up to 5 years)
- Duration of response(patients with objective response (confirmed CR or PR as best overall response) as the interval between dates of first documentation of objective response and first documentation of progressive disease up to 5 years)
- Change tumor-infiltrating lymphocytes (TILs)(baseline and progression/treatment discontinuation up to 5 years)