Clinical Trials /

A Phase II Randomized Trial of Immunotherapy Plus Radiotherapy in Metastatic Genitourinary Cancers

NCT03115801

Description:

The trial is open to patients who have metastatic renal cell carcinoma/urothelial (bladder) carcinoma with at least 2 measurable sites of disease. All eligible patients will be randomly assigned to immunotherapy(nivolumab/atezolizumab/pembrolizumab) versus immunotherapy (nivolumab/atezolizumab/pembrolizumab) plus radiotherapy, 10 Gy x3 (conformally or by intensity modulation radiation therapy/Image-guided radiation therapy (IMRT/IGRT) to maximally spare normal tissue), to one of their measurable lesions.

Related Conditions:
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase II Randomized Trial of Immunotherapy Plus Radiotherapy in Metastatic Genitourinary Cancers
  • Official Title: A Phase II Randomized Controlled Trial of Programmed Death -1/Programmed Death Ligand-1(PD-1/PDL-1) Axis Blockade Versus PD-1/PDL-1 Axis Blockade Plus Radiotherapy in Metastatic Genitourinary (Renal/Urothelial) Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 1606017369
  • NCT ID: NCT03115801

Conditions

  • Metastatic Renal Cell Carcinoma
  • Metastatic Urothelial Carcinoma

Interventions

DrugSynonymsArms
NivolumabImmunotherapyArm A - immunotherapy alone
AtezolizumabTecentriqArm A - immunotherapy alone
PembrolizumabKeytrudaArm A - immunotherapy alone

Purpose

The trial is open to patients who have metastatic renal cell carcinoma/urothelial (bladder) carcinoma with at least 2 measurable sites of disease. All eligible patients will be randomly assigned to immunotherapy(nivolumab/atezolizumab/pembrolizumab) versus immunotherapy (nivolumab/atezolizumab/pembrolizumab) plus radiotherapy, 10 Gy x3 (conformally or by intensity modulation radiation therapy/Image-guided radiation therapy (IMRT/IGRT) to maximally spare normal tissue), to one of their measurable lesions.

Detailed Description

      The trial is open to patients who have metastatic renal cell carcinoma/urothelial (bladder)
      carcinoma with at least 2 measurable sites of disease. All eligible patients will be randomly
      assigned to immunotherapy(nivolumab/atezolizumab/pembrolizumab) versus immunotherapy
      (nivolumab/atezolizumab/pembrolizumab) plus radiotherapy, 10 Gy x3 (conformally or by
      IMRT/IGRT to maximally spare normal tissue), to one of their measurable lesions. For patients
      assigned to the immunotherapy plus radiotherapy arm, immunotherapy treatment starts with the
      first radiotherapy fraction. Nivolumab will be given every 2 weeks for patients with
      metastatic renal cell cancer and atezolizumab/pembrolizumab will be given every 3 weeks for
      patients with metastatic urothelial cancer. Patients will be re-imaged at 9 week (year 1) or
      12 week (years 2-3) intervals and evaluated for response (defined as an objective response of
      measurable metastatic sites outside the radiation field). This response will be evaluated
      with CT scans in non-irradiated measurable metastatic sites per RECIST version 1.1. Patients
      will continue to receive their respective immunotherapies for up to three years or until
      disease progression or until a dose limiting toxicity is reached.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A - immunotherapy aloneActive ComparatorPatients with Renal Cell carcinoma will receive Nivolumab alone Days 1, 15, 29, 43 and 57. Patients with Urothelial cancer will receive Atezolizumab or Pembrolizumab on Days 1, 22, 43 and 64.
  • Nivolumab
  • Atezolizumab
  • Pembrolizumab
Arm B - Radiation & immunotherapyActive ComparatorRadiation is given to one lesion, 30 Gy in 3 fractions of 10 Gy, every other day. On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days.
  • Nivolumab
  • Atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Ability to understand and the willingness to sign a written informed consent document;

          2. Any prior therapy is permitted except prior therapy with PD1/PDL1 inhibitor.

          3. Histologic diagnosis of metastatic renal cell carcinoma or urothelial cancer;

          4. Patients must have at least 2 distinct measurable metastatic sites at least 1 cm or
             larger in their largest diameter per RECIST 1.1

          5. Patients must have adequate organ and marrow function as defined by initial laboratory
             tests.

          6. At least 2 weeks since last chemotherapy and 4 weeks since last immunotherapy
             treatment.

          7. Performance status Eastern cooperative oncology group (ECOG) 0-1

          8. Men and women, ages > 18 years of age.

          9. Life expectancy > 3 months

         10. Stable brain metastases for at least 4 weeks and not steroid dependent

         11. Women of childbearing potential (WOCBP) must be using an adequate method of
             contraception to avoid pregnancy throughout the study and for up to 8 weeks after the
             study in such a manner that the risk of pregnancy is minimized. Should a woman become
             pregnant or suspect she is pregnant while she is enrolled in this study, she should
             inform her treating physician immediately.

        Exclusion Criteria:

          1. Patients having no lesions outside the field of radiation thus nullifying the ability
             to measure an abscopal effect;

          2. Any other malignancy from which the patient has been disease-free for less than 5
             years, with the exception of adequately treated and cured basal or squamous cell skin
             cancer, superficial bladder cancer or carcinoma in situ of the cervix;

          3. Autoimmune/auto inflammatory disease: Patients with a history of inflammatory bowel
             disease are excluded from this study as are patients with a history of symptomatic
             disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma],
             Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis];

          4. Any underlying medical or psychiatric condition, which in the opinion of the
             Investigator, will make the administration of study drug hazardous or obscure the
             interpretation of adverse events (AEs), such as a condition associated with frequent
             diarrhea;

          5. Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to
             one month prior to or after any dose of PD-1/PDL-1 blocking antibody).

          6. A history of prior treatment with PD-1/PDL-1blocking antibody;

          7. Patients who have had immunotherapy within 4 weeks prior to entering the study.

          8. Concomitant therapy with any of the following: interleukin -2 (IL-2), interferon or
             other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive
             agents; other investigation therapies; or chronic use of systemic corticosteroids;

          9. Patients undergoing therapy with other investigational agents or other chemotherapy
             agents;

         10. Women who:

               1. are unwilling or unable to use an acceptable method to avoid pregnancy for the
                  entire study period and for at least 8 weeks after cessation of study drug, or

               2. have a positive pregnancy test at baseline, or

               3. are pregnant or breastfeeding

         11. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
             treatment of either a psychiatric or physical (e.g., infectious) illness
      
Maximum Eligible Age:90 Years
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:best overall response rates of immunotherapy alone and of immunotherapy plus radiotherapy(to a single metastatic site).
Time Frame:from 96 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:progression free survival
Time Frame:from 96 weeks
Safety Issue:
Description:
Measure:toxicities related to immunotherapy and immunotherapy plus radiotherapy treatment groups
Time Frame:from 96 weeks
Safety Issue:
Description:
Measure:overall survival
Time Frame:from 96 weeks
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Weill Medical College of Cornell University

Last Updated

September 5, 2019