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Low Dose, Reduced Frequency Nivolumab for the Treatment of Unresectable or Metastatic Cancer, AFFORD IO Trial

ConditionsClinical Stage III Cutaneous Melanoma AJCC v8Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8Clinical Stage IV Cutaneous Melanoma AJCC v8Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8Hodgkin LymphomaKaposi SarcomaMetastatic Acral Lentiginous MelanomaMetastatic Basal Cell CarcinomaMetastatic Cervical CarcinomaMetastatic Clear Cell Renal Cell CarcinomaMetastatic Colorectal CarcinomaMetastatic Cutaneous MelanomaMetastatic Head and Neck Squamous Cell CarcinomaMetastatic Kaposi SarcomaMetastatic Lung Non-Small Cell CarcinomaMetastatic Malignant Solid NeoplasmMetastatic Merkel Cell CarcinomaMetastatic Mucosal MelanomaMetastatic Skin Squamous Cell CarcinomaMetastatic Urothelial CarcinomaStage III Cervical Cancer AJCC v8Stage III Colorectal Cancer AJCC v8Stage III Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8Stage III Lung Cancer AJCC v8Stage III Renal Cell Cancer AJCC v8Stage IV Cervical Cancer AJCC v8Stage IV Colorectal Cancer AJCC v8Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8Stage IV Lung Cancer AJCC v8Stage IV Renal Cell Cancer AJCC v8Unresectable Acral Lentiginous MelanomaUnresectable Basal Cell CarcinomaUnresectable Cervical CarcinomaUnresectable Clear Cell Renal Cell CarcinomaUnresectable Colorectal CarcinomaUnresectable Cutaneous MelanomaUnresectable Head and Neck Squamous Cell CarcinomaUnresectable Lung Non-Small Cell CarcinomaUnresectable Malignant Solid NeoplasmUnresectable Merkel Cell CarcinomaUnresectable Mucosal MelanomaUnresectable Skin Squamous Cell CarcinomaUnresectable Urothelial Carcinoma
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorFred Hutchinson Cancer Center

About this trial

This phase II trial studies how well low dose, reduced frequency nivolumab works in treating patients with cancer that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Nivolumab is a type of immune checkpoint inhibitor (ICI). ICIs have revolutionized the treatment of numerous cancers with remarkable improvement in participant outcomes. However, accessibility of ICIs is extremely poor on a global scale, mainly due to high costs. Previous research has suggested that these drugs can be given at lower doses and reduced frequency than their approved dosing regimens, with similar results. Giving nivolumab at a lower dose and less often may help reduce the cost of therapy, improve immunotherapy accessibility, and therefore improve survival outcomes globally.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participants are eligible if they have one of these histologically confirmed, unresectable or metastatic cancer types listed below, based upon historical responsiveness to anti-PD-(L)1 agents

Non-small cell lung cancer (NSCLC) with documented PD-L1 expression (combined positive score [CPS] ≥ 1) (NOTE: Participants with known driver oncogenic mutations/rearrangements, including EGFR, ALK and ROS-1, will be excluded.)

Head and neck squamous cell carcinoma (HNSCC) with documented PD-L1 expression (CPS ≥ 1)

Clear cell renal cell carcinoma (ccRCC) (NOTE: Other subtypes may be permitted after approval by the Medical Monitor)

Disqualifiers

Prior exposure to any immune-checkpoint inhibitor for any reason

Residual adverse event(s) from prior therapy grade > 1 (National Cancer Institute [NCI]-Common Terminology Criteria for Adverse Events [CTCAE] v6.0) that could interfere with study endpoints or put participant safety at risk, as determined by the treating investigator

Known active central nervous system (CNS) metastases and/or prior history of leptomeningeal cancer involvement

Known history of another active malignancy (besides the eligible cancer diagnosis) within the last 3 years from day 1 of nivolumab that could interfere with study endpoints or put participant safety at risk. (NOTE: Exception will be made for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ [skin, bladder, cervical, colorectal, breast] or low grade prostatic intraepithelial neoplasia or grade 1 prostate cancer. Any other neoplasm, which has been treated adequately and is adjudged by the treating investigator to have a low risk of progression during the study, could be enrolled only after approval from the medical monitor.)

Trial design

Design model

Single group

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo collection of urine and/or blood samples

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Nivolumab

    Biological/Vaccine

    Given IV

Treatment groups

50 Participants
are divided into 1 treatment group
Group A: Treatment (low dose, reduced frequency nivolumab)Experimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Objective response

Defined as the best objective response of complete response (CR) or partial response (PR), as determined by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.

Time frame
Up to 4 years after completion of study treatment

Secondary outcomes

1

Duration of response (DOR)

Will be assessed per RECIST 1.1. The Kaplan-Meier (KM) technique will be used to obtain estimates of DOR. For event-based survival analyses in participants without documentation of the event, survival will be censored on the last date the participant was known to be event free. The standard error of the KM estimates will be computed using the Greenwood formula (Kalbfleisch \& Prentice, 2002), and standard errors from the matrix form of Greenwood's formula for cumulative incidence estimates. Median time to event, if reached, will be presented with a 90% confidence interval based on the Brookmeyer and Crowley method (Kalbfleisch \& Prentice, 2002).

Time frame
From the earliest date of disease response (CR or PR) until the earliest date of disease progression, or the date of death from any cause, assessed up to 4 years after completion of study treatment
2

Disease control

Defined as achievement of CR, PR, or stable disease as a patient's best objective response to the study treatment, per RECIST v1.1. For event-based survival analyses in participants without documentation of the event, survival will be censored on the last date the participant was known to be event free. The standard error of the KM estimates will be computed using the Greenwood formula (Kalbfleisch \& Prentice, 2002), and standard errors from the matrix form of Greenwood's formula for cumulative incidence estimates. Median time to event, if reached, will be presented with a 90% confidence interval based on the Brookmeyer and Crowley method (Kalbfleisch \& Prentice, 2002).

Time frame
Up to 4 years after completion of study treatment
3

Progression free survival (PFS)

The KM technique will be used to obtain estimates of PFS. For event-based survival analyses in participants without documentation of the event, survival will be censored on the last date the participant was known to be event free. The standard error of the KM estimates will be computed using the Greenwood formula (Kalbfleisch \& Prentice, 2002), and standard errors from the matrix form of Greenwood's formula for cumulative incidence estimates. Median time to event, if reached, will be presented with a 90% confidence interval based on the Brookmeyer and Crowley method (Kalbfleisch \& Prentice, 2002).

Time frame
From date of first dose of study treatment until the earliest date of disease progression, or the date of death from any cause, assessed up to 4 years after completion of study treatment
4

Overall survival (OS)

The KM technique will be used to obtain estimates of OS. For event-based survival analyses in participants without documentation of the event, survival will be censored on the last date the participant was known to be event free. The standard error of the KM estimates will be computed using the Greenwood formula (Kalbfleisch \& Prentice, 2002), and standard errors from the matrix form of Greenwood's formula for cumulative incidence estimates. Median time to event, if reached, will be presented with a 90% confidence interval based on the Brookmeyer and Crowley method (Kalbfleisch \& Prentice, 2002).

Time frame
From date of first dose of study treatment until the date of death from any cause, assessed up to 4 years after completion of study treatment

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Fred Hutchinson Cancer Center

Lead sponsor

The Wayne D. Kuni and Joan E. Kuni Foundation

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: