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Evaluation of the Length of Treatment With PD-1/PD-L1 Inhibitors in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04157985
Recruitment Status : Recruiting
First Posted : November 8, 2019
Last Update Posted : January 12, 2022
Sponsor:
Information provided by (Responsible Party):
Antoinette J Wozniak, University of Pittsburgh

Study Description
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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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors NSCLC Bladder Cancer HNSCC Renal Cancer Melanoma Anal Cancer Colorectal Cancer Cholangiocarcinoma Gastric Cancer Hepatocellular Carcinoma Merkel Cell Carcinoma Cervical Cancer Drug: Continue PD-1/PD-L1 Inhibitors treatment Other: Discontinue PD-1/PD-L1-1 inhibitor Phase 3

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 578 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Non-inferiority Trial Evaluating the Length of Treatment With PD-1/PD-L1 Inhibitors in Patients With Advanced Solid Tumors
Actual Study Start Date : November 15, 2019
Estimated Primary Completion Date : October 2026
Estimated Study Completion Date : October 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Continue Treatment with PD-1/PD-L1 inhibitor
Continued standard of care treatment with PD-1/PD-L1 -1 checkpoint inhibitor after 12 months of checkpoint inhibitor treatment.
 Drug: Continue PD-1/PD-L1 Inhibitors treatment
Continued treatment with PD-1/PD-L1-1 inhibitor
Other Names:
  • Keytruda (pembrolizumab)
  • Optiva (nivolumab)
  • Tecentriq (atezolizumab)
  • Yervoy (ipilimumab)
  • LIBTAYO (cemiplimab)
Experimental: Discontinue Treatment with PD-1/PD-L1-1 inhibitor
Discontinued standard of care treatment with PD-1/PD-L1 -1 checkpoint inhibitor after 12 months of checkpoint inhibitor treatment.
 Other: Discontinue PD-1/PD-L1-1 inhibitor
Discontinued treatment with PD-1/PD-L1-1 inhibitor


Outcome Measures
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Primary Outcome Measures :
  1. Time to next treatment [ Time Frame: Up to 36 months ]
    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.

  2. Progression-free Survival (PFS) (at between 2-3.9 months) [ Time Frame: Between 2 months and 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.

  3. Progression-free Survival (PFS) (at between 4-7.9 months) [ Time Frame: Between 4 months and 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.

  4. Progression-free Survival (PFS) [ Time Frame: Up to 36 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.


Secondary Outcome Measures :
  1. Incidence of irAEs (Immune-Related Adverse Events) [ Time Frame: Up to 36 months ]
    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.

  2. Overall Survival (OS) [ Time Frame: Up to 36 months ]
    The length of time from the start of treatment that patients are still alive.

  3. Best Objective Response (BOR) [ Time Frame: Up to 36 months ]
    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).


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04157985


Contacts
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Contact: Ruth Jen, BSN ruthj2@upmc.edu ruthj2@upmc.edu

Locations
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United States, Pennsylvania
UPMC Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Jennifer Ruth, BSN    412-623-8963    ruthj2@upmc.edu   
Contact: BSN         
Principal Investigator: Antoinette J Wozniak, MD, FACP         
Sponsors and Collaborators
Antoinette J Wozniak
Investigators
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Principal Investigator: Antoinette J Wozniak, MD, FACP UPMC Hillman Cancer Center
More Information
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Responsible Party: Antoinette J Wozniak, Professor, Department of Otolaryngology, of Immunology, and of Radiation Oncology, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT04157985    
Other Study ID Numbers: 19-135
First Posted: November 8, 2019    Key Record Dates
Last Update Posted: January 12, 2022
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Carcinoma, Merkel Cell
Carcinoma
Cholangiocarcinoma
Anus Neoplasms
Kidney Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
 Intestinal Diseases
Rectal Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Adenocarcinoma
Urogenital Neoplasms
Urologic Neoplasms
Urologic Diseases
Rectal Neoplasms
Anus Diseases
Kidney Diseases
Polyomavirus Infections
DNA Virus Infections