5-Azacitidine Plus PD-1/PD-L1 Inhibitor With PD-1/PD-L1 Refractory Tumors
Purpose
This is a Phase I study to determine the optimal biological dose (OBD) of 5-Azacitidine in combination with PD-1/PD-L1 inhibitors in patients with tumors refractory to PD-1/PD-L1 inhibitors, for which such treatments have been approved.
Conditions
- Solid Tumor
- Locally Advanced Solid Tumor
- Metastatic Tumor
Eligibility
- Eligible Ages
- Between 18 Years and 99 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Written and voluntary informed consent. - At least 18 years of age or older. - Histologically and radiologically confirmed locally advanced or metastatic unresectable solid tumor malignancy for which PD-1 or PD-L1 therapy is already approved by the FDA. Locally advanced is defined as unresectable in the opinion of the treating physician. A repeat biopsy is required if previous biopsy tissue is unavailable. - At least one Response Evaluation Criteria in Solid Tumors (RECIST 1.1) - defined target lesion. - Eastern Cooperative Oncology Group (ECOG) performance status of 0 (fully active, able to carry on all pre-disease performance without restriction), 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, such as light housework or office work), or 2 (ambulatory and capable of self-care but unable to carry out any work activities, spending more than 50% of waking hours up and about). - Documented progression on PD1 or PD-L1 inhibitors. - Recovery from any acute toxicity associated with prior therapy to grade 1. - Renal function (creatinine level within normal institutional limit, or creatinine clearance >15 mL/min/1.73 m2 for patients with creatinine levels above institutional normal, calculated using the Cockcroft-Gault formula). - Liver function (AST/ALT <3.0 X institutional upper limit of normal OR <5 X institutional upper limit of normal in cases of liver metastasis; total bilirubin ≤ 1.5 times upper limit of normal). - Adequate hematological lab values including: - Absolute Neutrophil Count (ANC) ≥ 1.0 X 109/L - Platelets ≥ 100X109/L - Hemoglobin ≥ 7.0 g/dL - Female subjects of childbearing potential and non-sterilized male subjects who intend to be sexually active during the study must agree to use a highly effective method of contraception from time of screening, throughout the whole duration of the drug treatment, and during the 6-month post-treatment washout period. - Patients may have previously received a hypomethylating agent, as long as it was not given in combination with ipilimumab. - Patients may have previously received ipilimumab but must have relapsed or progressed while on therapy. - Patients must have adequate archival tissue available for the purpose of downstream methylation status assessment, immunohistochemistry, RNA expression (10 slides at 5µM). If archival tissue is not available, a repeat biopsy is required.
Exclusion Criteria
- Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen. - Patients with active, untreated metastases in the central nervous system. - Patients who are pregnant or breastfeeding. - Patients who have an active infection. - Patients with significant hematologic, hepatic, and renal function impairment. - Patients who are being treated for any concurrent medical condition requiring the use of systemic steroids or history of long-term use of systemic steroids. - Patients who have a history of inflammatory bowel disease or a history of symptomatic autoimmune disease. - Patients who have had any major surgical procedure or significant traumatic injury within 28 days prior to study enrollment. - Patients who have received chemotherapy, immunosuppressive agents or any investigational drug within 28 days prior to starting the study drugs. - Patients who have any underlying medical condition which, in the treating physician's opinion, will make the administration of study drugs hazardous or obscure the interpretation of adverse events.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental 5-Azacitidine Plus PD-1/PD-L1 inhibitor |
This Phase I study will assess 6 doses of 5-Azacitidine (5, 10, 15, 25, 50 and 75 mg/m2) in combination with a PD1/PD-L1 inhibitor. The PD1/PD-L1 inhibitor will be given at standard of care dosing approved by the FDA for this indication. Inhibitors approved for study indications include Pembrolizumab, Nivolumab, and Cemiplimab. |
|
Recruiting Locations
University of Iowa Health Care
Iowa City, Iowa 52242
Iowa City, Iowa 52242
More Details
- Status
- Recruiting
- Sponsor
- Mohammed Milhem
Detailed Description
This is a Phase I study to determine the optimal biological dose (OBD) of 5-Azacitidine in combination with PD-1/PD-L1 inhibitors in patients with tumors refractory to PD-1/PD-L1 inhibitors, for which such treatments have been approved. This Phase I study will assess 6 doses of 5-Azacitidine (5, 10, 15, 25, 50 and 75 mg/m2) in combination with a PD1/PD-L1 inhibitor. The PD1/PD-L1 inhibitor will be given at standard of care dosing approved by the FDA for this indication.