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

NCT03115801 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 1606017369
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Renal Cell Carcinoma; Metastatic Urothelial Carcinoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Best Overall Response Rates of Immunotherapy Alone and of Immunotherapy Plus Radiotherapy (to a Single Metastatic Site).

  from 96 weeks

• Assess the Difference in Participants for the Best Overall Response Between the Two Groups, Immunotherapy Alone and of Immunotherapy Plus Radiotherapy(to a Single Metastatic Site).

  from 96 weeks

Secondary Outcomes (3)

• Number of Participants With Progression Free Survival

  from 96 weeks

• Number of Participants Who Experienced Toxicities Related to Immunotherapy and Immunotherapy Plus Radiotherapy Treatment Groups

  from 96 weeks

• Participants Will be Measured for Overall Survival

  from 96 weeks

Study Arms (2)

Arm A - immunotherapy alone

ACTIVE COMPARATOR

Patients 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.

Drug: Nivolumab; Drug: Atezolizumab; Drug: Pembrolizumab

Arm B - Radiation & immunotherapy

ACTIVE COMPARATOR

Radiation 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.

Drug: Nivolumab; Drug: Atezolizumab; Radiation: Radiation & immunotherapy

Interventions

Nivolumab DRUG

Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57.

Also known as: Immunotherapy

Arm A - immunotherapy alone; Arm B - Radiation & immunotherapy

Atezolizumab DRUG

Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.

Also known as: Tecentriq

Arm A - immunotherapy alone; Arm B - Radiation & immunotherapy

Radiation & immunotherapy RADIATION

Radiation is given to one lesion, 30 Gray (Gy) in 3 fractions of 10 Gy each. over a one week interval (with a minimum of 36hrs between each fraction). On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Patients will receive radiation on Day 1 and immunotherapy will be given ± 24hr from Day 1.

Arm B - Radiation & immunotherapy

Pembrolizumab DRUG

Pembrolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.

Also known as: Keytruda

Arm A - immunotherapy alone

Eligibility Criteria

• Age: 19 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document;
• Any prior therapy is permitted except prior therapy with PD1/PDL1 inhibitor.
• Histologic diagnosis of metastatic renal cell carcinoma or urothelial cancer;
• Patients must have at least 2 distinct measurable metastatic sites at least 1 cm or larger in their largest diameter per RECIST 1.1
• Patients must have adequate organ and marrow function as defined by initial laboratory tests.
• At least 2 weeks since last chemotherapy and 4 weeks since last immunotherapy treatment.
• Performance status Eastern cooperative oncology group (ECOG) 0-1
• Men and women, ages \> 18 years of age.
• Life expectancy \> 3 months
• Stable brain metastases for at least 4 weeks and not steroid dependent
• 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.

You may not qualify if:

• Patients having no lesions outside the field of radiation thus nullifying the ability to measure an abscopal effect;
• 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;
• 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 \[e.g., Wegener's Granulomatosis\];
• 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;
• 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).
• A history of prior treatment with PD-1/PDL-1blocking antibody;
• Patients who have had immunotherapy within 4 weeks prior to entering the study.
• 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;
• Patients undergoing therapy with other investigational agents or other chemotherapy agents;
• Women who:
• 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
• have a positive pregnancy test at baseline, or
• are pregnant or breastfeeding
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (1)

Weill Cornell Medicine - New York Presbyterian Hospital

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Carcinoma, Transitional Cell

Interventions

Nivolumab; Immunotherapy; atezolizumab; Radiation; pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunomodulation; Biological Therapy; Therapeutics; Physical Phenomena

Limitations and Caveats

The clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results.

Results Point of Contact

• Title: Sharanya Chandrasekhar
• Organization: Weill Cornell Medicine

shc2043@med.cornell.edu

6469623110

Study Officials

• Himanshu Nagar, M.D.

  Weill Cornell Medicine - New York Presbyterian Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2016
• First Posted: April 14, 2017
• Study Start: November 1, 2016
• Primary Completion: October 13, 2020
• Study Completion: October 13, 2020
• Last Updated: September 22, 2021
• Results First Posted: September 22, 2021

Record last verified: 2021-08

Locations

US (1)