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A Study of Atezolizumab in Combination With Bevacizumab in Untreated Locally Advanced or Metastatic Clear Cell or Non-Clear Cell Renal Cell Carcinoma

Primary Purpose

Renal Cell Carcinoma

Status

Withdrawn

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

Atezolizumab

Bevacizumab

About this trial

This is an interventional treatment trial for Renal Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Unresectable, advanced or metastatic RCC with clear cell or non-clear cell histology
No prior treatment with active or experimental systemic agents for RCC
Measurable and/or non-measurable but evaluable baseline disease per RECIST v1.1
Confirmed diagnosis of RCC
Karnofsky Performance Score (KPS) ≥ 60
Adequate hematologic and end-organ function
Patients with asymptomatic CNS metastases are eligible, provided they meet all of the following criteria:
- Evaluable disease outside the CNS
- No history of intracranial or spinal cord hemorrhage
- No evidence of significant vasogenic edema
- No stereotactic radiation within 7 days or whole-brain radiation or neurosurgical resection within 2 weeks before the start of study treatment
- Have had a screening CNS radiography ≥ 2 weeks since completion of radiotherapy or surgical resection
For women of childbearing potential: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating eggs
For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm

Exclusion Criteria:

Prior treatment for RCC with active or experimental systemic agents, including treatment in the neoadjuvant or adjuvant setting - Confirmed prior treatment with placebo in the (neo)adjuvant setting is allowed
Radiotherapy ongoing at the time of study entry
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) - Patients with indwelling catheters are allowed
Uncontrolled or symptomatic hypercalcemia - Patients who are currently receiving bisphosphonate therapy without current hypercalcemia are eligible
History of malignancy other than RCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
Life expectancy of < 12 weeks
History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan - History of radiation pneumonitis in the radiation field (fibrosis) is permitted
Active tuberculosis
Significant renal disorder requiring dialysis
Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
Patients with active hepatitis B or hepatitis C
Current treatment with anti-viral therapy for HBV
Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Atezolizumab + Bevacizumab

Arm Description

Participants will receive atezolizumab in combination with bevacizumab.

Outcomes

Primary Outcome Measures

Percentage of Participants with Adverse Events

Secondary Outcome Measures

Overall Survival (OS)

OS is defined as the time from enrolment in the study to death from any cause

Progression-Free survival (PFS)

PFS is defined as the time from enrolment in the study to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be assessed by the investigator according to RECIST v1.1 and modified RECIST (iRECIST)

Overall Response Rate (ORR)

ORR is defined as the proportion of patients with a best overall response of either complete response (CR) or partial response (PR). ORR will be assessed by the investigator according to RECIST v1.1 and iRECIST.

Disease Control Rate (DCR)

DCR is defined as the sum of the CR, PR and stable disease (SD) rates. DCR will be assessed by the investigator according to RECIST v1.1 and iRECIST.

Duration of Response (DoR)

DoR is defined as the time from first occurrence of a documented response to disease progression or death from any cause, whichever occurs first. DoR will be assessed by the investigator according to RECIST v1.1 and iRECIST.

PD-L1 Expression in Tumor Samples From the Tumor Tissue

Measured retrospectively by immunohistochemistry (IHC).

Change From Baseline in the Single Item (GP5) of the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy-Kidney Symptom Index 19 (FKSI-19), Version 2

Change From Baseline in MD Anderson Symptom Inventory (MDASI) Core and MDASI-RCC Module

Time to Deterioration of Daily Functioning

Time to deterioration of daily functioning is defined as the time from enrolment to first ≥ 2-point increase above baseline in MDASI interference score.

Full Information

NCT ID

NCT03693573

First Posted

September 25, 2018

Last Updated

November 13, 2018

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT03693573

Brief Title

A Study of Atezolizumab in Combination With Bevacizumab in Untreated Locally Advanced or Metastatic Clear Cell or Non-Clear Cell Renal Cell Carcinoma

Official Title

An Open Label, Phase IIIB, Single Arm, Multicenter Safety Study of Atezolizumab in Combination With Bevacizumab in Untreated Locally Advanced or Metastatic Clear Cell or Non-Clear Cell Renal Cell Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

November 2018

Overall Recruitment Status

Withdrawn

Why Stopped

In the context of the ongoing evaluation of our data, we have determined that there is no need to generate additional safety data at this time in the 1L mRCC pa

Study Start Date

January 11, 2019 (Anticipated)

Primary Completion Date

August 14, 2021 (Anticipated)

Study Completion Date

January 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Study MO39939 is an open-label, single-arm, multicenter trial in patients with unresectable, locally-advanced or metastatic, clear or non-clear cell renal cell carcinoma (RCC) who have not received prior systemic therapy (who are treatment naïve in either the [neo]adjuvant or advanced/metastatic setting for clear and non-clear cell RCC). The study consists of a Screening Period, a Treatment Period, an End of Treatment Visit occurring approximately 30 days after the last dose of study medication, and a Follow-Up Period of 4 years after last patient enrolled.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Renal Cell Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Atezolizumab + Bevacizumab

Arm Type

Experimental

Arm Description

Participants will receive atezolizumab in combination with bevacizumab.

Intervention Type

Drug

Intervention Name(s)

Atezolizumab

Other Intervention Name(s)

Tecentriq

Intervention Description

Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle. Administration of study drugs will continue until unacceptable toxicity; loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status; investigator or patient decision to withdraw from therapy; or death (whichever occurs first).

Intervention Type

Drug

Intervention Name(s)

Bevacizumab

Other Intervention Name(s)

Avastin

Intervention Description

Bevacizumab will be administered by IV infusion at 15 mg/kg on Day 1 of each 21-day cycle. Administration of study drugs will continue until unacceptable toxicity; loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status; investigator or patient decision to withdraw from therapy; or death (whichever occurs first).

Primary Outcome Measure Information:

Title

Percentage of Participants with Adverse Events

Time Frame

Up to 6 years

Secondary Outcome Measure Information:

Title

Overall Survival (OS)

Description

OS is defined as the time from enrolment in the study to death from any cause

Time Frame

Up to 6 years

Title

Progression-Free survival (PFS)

Description

Time Frame

Up to 6 years

Title

Overall Response Rate (ORR)

Description

Time Frame

Up to 6 years

Title

Disease Control Rate (DCR)

Description

DCR is defined as the sum of the CR, PR and stable disease (SD) rates. DCR will be assessed by the investigator according to RECIST v1.1 and iRECIST.

Time Frame

Up to 6 years

Title

Duration of Response (DoR)

Description

Time Frame

Up to 6 years

Title

PD-L1 Expression in Tumor Samples From the Tumor Tissue

Description

Measured retrospectively by immunohistochemistry (IHC).

Time Frame

At baseline

Title

Change From Baseline in the Single Item (GP5) of the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy-Kidney Symptom Index 19 (FKSI-19), Version 2

Time Frame

Before dosing on Day 1 of each cycle, at the End-of-Treatment visit, and at 3, 6, and 9 months after the End-of-Treatment visit. End-of-Treatement visit occurring approximately 30 days after last cycle treatment date. Each cycle is 21 days.

Title

Change From Baseline in MD Anderson Symptom Inventory (MDASI) Core and MDASI-RCC Module

Time Frame

Before dosing on Day 1 of each cycle, at the End-of-Treatment visit, and at 3, 6, and 9 months after the End-of-Treatment visit. End-of-Treatment visit occurring approximately 30 days after last cycle treatment date. Each cycle is 21 days.

Title

Time to Deterioration of Daily Functioning

Description

Time to deterioration of daily functioning is defined as the time from enrolment to first ≥ 2-point increase above baseline in MDASI interference score.

Time Frame

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Unresectable, advanced or metastatic RCC with clear cell or non-clear cell histology No prior treatment with active or experimental systemic agents for RCC Measurable and/or non-measurable but evaluable baseline disease per RECIST v1.1 Confirmed diagnosis of RCC Karnofsky Performance Score (KPS) ≥ 60 Adequate hematologic and end-organ function Patients with asymptomatic CNS metastases are eligible, provided they meet all of the following criteria: Evaluable disease outside the CNS No history of intracranial or spinal cord hemorrhage No evidence of significant vasogenic edema No stereotactic radiation within 7 days or whole-brain radiation or neurosurgical resection within 2 weeks before the start of study treatment Have had a screening CNS radiography ≥ 2 weeks since completion of radiotherapy or surgical resection For women of childbearing potential: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating eggs For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm Exclusion Criteria: Prior treatment for RCC with active or experimental systemic agents, including treatment in the neoadjuvant or adjuvant setting - Confirmed prior treatment with placebo in the (neo)adjuvant setting is allowed Radiotherapy ongoing at the time of study entry Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) - Patients with indwelling catheters are allowed Uncontrolled or symptomatic hypercalcemia - Patients who are currently receiving bisphosphonate therapy without current hypercalcemia are eligible History of malignancy other than RCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer Life expectancy of < 12 weeks History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan - History of radiation pneumonitis in the radiation field (fibrosis) is permitted Active tuberculosis Significant renal disorder requiring dialysis Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study Patients with active hepatitis B or hepatitis C Current treatment with anti-viral therapy for HBV Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

12. IPD Sharing Statement

Learn more about this trial

A Study of Atezolizumab in Combination With Bevacizumab in Untreated Locally Advanced or Metastatic Clear Cell or Non-Clear Cell Renal Cell Carcinoma

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