Back to resultsEvaluating Length of Treatment With PD-1/PD-L1 Inhibitor in Advanced Solid Tumors
Primary Purpose
Advanced Solid Tumors, NSCLC, Bladder Cancer
Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Continue PD-1/PD-L1 Inhibitors treatment
Discontinue PD-1/PD-L1-1 inhibitor
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Solid Tumors
Eligibility Criteria
Inclusion Criteria:
- All patients must have an advanced solid tumor malignancy (specifically NSCLC, bladder, HNSCC, renal, melanoma, cervical, Merkel cell, MMR/MSI [colon, rectal, cholangio, esophageal, ovarian, uterine], anal, gastric and GE junction, hepatocellular, triple negative breast cancer) that is being treated with a PD-1/PD-L1 inhibitor including pembrolizumab, nivolumab, atezolizumab, durvalumab, or avelumab according to standard of care treatment.
- Patients who initially started treatment with another agent in combination with the PD-1/PD-L1 inhibitor, i.e. chemotherapy, ipilumumab, are eligible.
- Patients must have at least stable disease as evidenced by scans performed within 6 weeks of randomization.
- Signed Informed consent allowing randomization to stopping immunotherapy at 1 year ± 4 weeks versus continued treatment beyond 1 year.
- Patients can have measurable or non-measurable disease per iRECIST.
- Patients cannot be enrolled in a clinical trial.
Exclusion Criteria:
- Patients with documented progressive disease prior to randomization.
- Patients with an immune-related toxicity preventing the continuation of treatment beyond 1 year at the treating physician's discretion.
Sites / Locations
- UPMC Hillman Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Continue Treatment with PD-1/PD-L1 inhibitor
Discontinue Treatment with PD-1/PD-L1-1 inhibitor
Arm Description
Continued standard of care treatment with PD-1/PD-L1 -1 checkpoint inhibitor after 12 months of checkpoint inhibitor treatment.
Discontinued standard of care treatment with PD-1/PD-L1 -1 checkpoint inhibitor after 12 months of checkpoint inhibitor treatment.
Outcomes
Primary Outcome Measures
Time to next treatment
In patients who have already been treated with a PD-1 or PD-L1 inhibitor for one year, the difference in progression-free survival (time to next treatment, progression or death, whichever occurs first) between patients who stop treatment and patients who continue treatment.
Progression-free Survival (PFS) (at between 2-3.9 months)
The (median) length of time from the initial date of treatment to the date of documented progression, or the date of death due to any cause (in the absence of progression, whichever occurs first), with progression defined by RECIST v1.1.Per RECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.
Progression-free Survival (PFS) (at between 4-7.9 months)
The (median) length of time from the initial date of treatment to the date of documented progression, or the date of death due to any cause (in the absence of progression, whichever occurs first), with progression defined by RECIST v1.1.Per RECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.
Progression-free Survival (PFS)
The (median) length of time from the initial date of treatment to the date of documented progression, or the date of death due to any cause (in the absence of progression, whichever occurs first), with progression defined by RECIST v1.1.Per RECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.
Secondary Outcome Measures
Incidence of irAEs (Immune-Related Adverse Events)
Proportion of participants in a disease stratum and treatment arm who experience at least one AE of any grade (per Common Terminology Criteria for Adverse Events (CTCAE v5.0)), at least possibly related to treatment in the categories of colitis, hepatitis, pnemonitis, hypophysitis or hypopituitarism, hypothyroidism, fatigue, diarrhea, rash, arthritis, arthralgia, back pain, musculoskeletal pain or myalgia, or any other category that is felt to be related to treatment.
Overall Survival (OS)
The length of time from the start of treatment that patients are still alive.
Best Objective Response (BOR)
Proportions of participants who restart for disease progression in each disease stratum, who experience a best objective response (progressive disease, stable disease, partial response, complete response) per RECIST v1.1 (Response Evaluation Criteria in Solid Tumors);Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to <10 mm;Partial Response (PR): ≥ 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters;Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, (reference smallest sum diameters);Progressive Disease (PD): ≥ 20% increase in the sum of diameters of target lesions (reference smallest sum diameters); the sum must also demonstrate an absolute increase of at least 5 mm; (appearance ≥ 1 new lesions is considered progression).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04157985
Brief Title
Evaluating Length of Treatment With PD-1/PD-L1 Inhibitor in Advanced Solid Tumors
Official Title
Evaluating Length of Treatment With PD-1/PD-L1 Inhibitor in Advanced Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 15, 2019 (Actual)
Primary Completion Date
October 2026 (Anticipated)
Study Completion Date
October 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jason J. Luke, MD
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Based on the overwhelming positive response to this survey and the large number of patients being treated with PD-1/PD-L1 therapy in the UPMC system, the investigators are proposing a trial that will randomize patients who have disease stability to stop treatment at 1 year or continue treatment until disease progression. The investigators anticipate that the results of this study will answer questions regarding the optimal duration of treatment. therapy.
Detailed Description
Within the UPMC system, approximately 2,300 patients received PD-1/PD-L1 therapy for a variety of advanced solid tumors within the past year. It is anticipated that this number will increase as the clinical indications for treatment with these agents also increase. The investigators conducted a survey of 60 Medical Oncologists within the UPMC system regarding their interest in a trial that will attempt to address the question of optimal length of PD-1/PD-L1 treatment. Fifty-two (86.7%) physicians indicated that they would participate in a clinical trial that had a primary goal of determining whether it was feasible to stop immunotherapy after 1 year of treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Tumors, NSCLC, Bladder Cancer, HNSCC, Renal Cancer, Melanoma, Anal Cancer, Colorectal Cancer, Cholangiocarcinoma, Gastric Cancer, Hepatocellular Carcinoma, Merkel Cell Carcinoma, Cervical Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
578 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Continue Treatment with PD-1/PD-L1 inhibitor
Arm Type
Active Comparator
Arm Description
Continued standard of care treatment with PD-1/PD-L1 -1 checkpoint inhibitor after 12 months of checkpoint inhibitor treatment.
Arm Title
Discontinue Treatment with PD-1/PD-L1-1 inhibitor
Arm Type
Experimental
Arm Description
Discontinued standard of care treatment with PD-1/PD-L1 -1 checkpoint inhibitor after 12 months of checkpoint inhibitor treatment.
Intervention Type
Drug
Intervention Name(s)
Continue PD-1/PD-L1 Inhibitors treatment
Other Intervention Name(s)
Keytruda (pembrolizumab), Optiva (nivolumab), Tecentriq (atezolizumab), Yervoy (ipilimumab), LIBTAYO (cemiplimab)
Intervention Description
Continued treatment with PD-1/PD-L1-1 inhibitor
Intervention Type
Other
Intervention Name(s)
Discontinue PD-1/PD-L1-1 inhibitor
Intervention Description
Discontinued treatment with PD-1/PD-L1-1 inhibitor
Primary Outcome Measure Information:
Title
Time to next treatment
Description
In patients who have already been treated with a PD-1 or PD-L1 inhibitor for one year, the difference in progression-free survival (time to next treatment, progression or death, whichever occurs first) between patients who stop treatment and patients who continue treatment.
Time Frame
Up to 36 months
Title
Progression-free Survival (PFS) (at between 2-3.9 months)
Description
The (median) length of time from the initial date of treatment to the date of documented progression, or the date of death due to any cause (in the absence of progression, whichever occurs first), with progression defined by RECIST v1.1.Per RECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.
Time Frame
Between 2 months and 3.9 months
Title
Progression-free Survival (PFS) (at between 4-7.9 months)
Description
The (median) length of time from the initial date of treatment to the date of documented progression, or the date of death due to any cause (in the absence of progression, whichever occurs first), with progression defined by RECIST v1.1.Per RECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.
Time Frame
Between 4 months and 7.9 months
Title
Progression-free Survival (PFS)
Description
The (median) length of time from the initial date of treatment to the date of documented progression, or the date of death due to any cause (in the absence of progression, whichever occurs first), with progression defined by RECIST v1.1.Per RECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.
Time Frame
Up to 36 months
Secondary Outcome Measure Information:
Title
Incidence of irAEs (Immune-Related Adverse Events)
Description
Proportion of participants in a disease stratum and treatment arm who experience at least one AE of any grade (per Common Terminology Criteria for Adverse Events (CTCAE v5.0)), at least possibly related to treatment in the categories of colitis, hepatitis, pnemonitis, hypophysitis or hypopituitarism, hypothyroidism, fatigue, diarrhea, rash, arthritis, arthralgia, back pain, musculoskeletal pain or myalgia, or any other category that is felt to be related to treatment.
Time Frame
Up to 36 months
Title
Overall Survival (OS)
Description
The length of time from the start of treatment that patients are still alive.
Time Frame
Up to 36 months
Title
Best Objective Response (BOR)
Description
Proportions of participants who restart for disease progression in each disease stratum, who experience a best objective response (progressive disease, stable disease, partial response, complete response) per RECIST v1.1 (Response Evaluation Criteria in Solid Tumors);Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to <10 mm;Partial Response (PR): ≥ 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters;Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, (reference smallest sum diameters);Progressive Disease (PD): ≥ 20% increase in the sum of diameters of target lesions (reference smallest sum diameters); the sum must also demonstrate an absolute increase of at least 5 mm; (appearance ≥ 1 new lesions is considered progression).
Time Frame
Up to 36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
All patients must have an advanced solid tumor malignancy (specifically NSCLC, bladder, HNSCC, renal, melanoma, cervical, Merkel cell, MMR/MSI [colon, rectal, cholangio, esophageal, ovarian, uterine], anal, gastric and GE junction, hepatocellular, triple negative breast cancer) that is being treated with a PD-1/PD-L1 inhibitor including pembrolizumab, nivolumab, atezolizumab, durvalumab, or avelumab according to standard of care treatment.
Patients who initially started treatment with another agent in combination with the PD-1/PD-L1 inhibitor, i.e. chemotherapy, ipilumumab, are eligible.
Patients must have at least stable disease as evidenced by scans performed within 6 weeks of randomization.
Signed Informed consent allowing randomization to stopping immunotherapy at 1 year ± 6 weeks versus continued treatment beyond 1 year.
Patients can have measurable or non-measurable disease per iRECIST.
Patients cannot be enrolled in a clinical trial.
Exclusion Criteria:
Patients with documented progressive disease prior to randomization.
Patients with an immune-related toxicity preventing the continuation of treatment beyond 1 year at the treating physician's discretion.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ruth Jen, BSN
Phone
ruthj2@upmc.edu
Email
ruthj2@upmc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jason Luke, MD
Organizational Affiliation
UPMC Hillman Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
UPMC Hillman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Ruth, BSN
Phone
412-623-8963
Email
ruthj2@upmc.edu
First Name & Middle Initial & Last Name & Degree
BSN
First Name & Middle Initial & Last Name & Degree
Jason Luke, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Evaluating Length of Treatment With PD-1/PD-L1 Inhibitor in Advanced Solid Tumors
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