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Anti-tumor antibiotic, Anti-metabolites

Durvalumab + Chemotherapy for Urothelial Carcinoma

Phase 2 & 3

Recruiting

Led By Jean H Hoffman-Censits

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patient must have a diagnosis of high grade upper tract urothelial carcinoma proven by biopsy within 12 weeks (84 days) prior to registration/randomization with one of the following: Upper urinary tract mass on cross-sectional imaging or Tumor directly visualized during upper urinary tract endoscopy before referral to medical oncology

NOTE: Biopsy is standard of care (SOC) and required for enrollment to study. This is vital for best practice

Must not have

Patient must not have received prior systemic anthracycline therapy

T1-4a N0 and no evidence of disease (NED) for more than 2 years from the latest therapy [e.g., radical surgery, transurethral resection of bladder tumor (TURBT), radiation, chemotherapy (neoadjuvant or adjuvant, or with radiation)]. Prior immune checkpoint inhibitor is not allowed.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from registration/randomization to death from any cause, assessed up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing whether adding durvalumab to chemotherapy will be more effective than chemotherapy alone in treating patients with upper urinary tract cancer before surgery.

Who is the study for?

Adults with high-grade upper urinary tract cancer who are fit for chemotherapy and surgery. They must have a life expectancy of at least 12 weeks, adequate organ function, no severe hearing loss or neuropathy, not be pregnant or breastfeeding, and willing to use contraception. Excluded if they have small cell/neuroendocrine carcinoma components in their cancer, other active cancers (with some exceptions), uncontrolled illnesses, recent major surgeries, certain autoimmune diseases or treatments.

What is being tested?

The trial is testing the addition of Durvalumab (an immunotherapy drug) to standard chemotherapy before surgery compared to chemotherapy alone. The goal is to see if combining Durvalumab with chemo can better shrink tumors before they're surgically removed.

What are the potential side effects?

Durvalumab may cause immune-related side effects like inflammation in various organs including lungs and intestines; infusion reactions; fatigue; potential harm to an unborn baby hence the need for contraception. Chemotherapy can cause hair loss, nausea/vomiting, increased risk of infection due to low blood counts.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I was diagnosed with a severe type of urinary tract cancer within the last 12 weeks.

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I understand a biopsy is necessary for my participation in the study.

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I can take care of myself and am up and about more than half of my waking hours.

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I had hepatitis C but am now treated with no detectable virus, or I am currently being treated with no detectable virus.

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I am 18 years old or older.

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I weigh more than 30 kilograms.

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My hepatitis B virus is undetectable with treatment.

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I have a tumor in my upper urinary tract seen on imaging or during an endoscopy.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have never been treated with anthracycline drugs.

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I've been cancer-free for over 2 years after treatment and haven't had immune therapy.

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I have a history of bladder cancer.

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I do not have any serious health issues that are not under control.

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I am taking no more than 10 mg/day of prednisone or its equivalent.

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My scans show no signs of cancer spread or large lymph nodes.

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My cancer is mostly urothelial and does not have small cell/neuroendocrine parts.

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I have a history of cancer that is not related to the bladder.

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I have not had radiation on more than 25% of my bone marrow.

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My cancer has not spread extensively to other parts of my body.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from registration/randomization to death from any cause, assessed up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from registration/randomization to death from any cause, assessed up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and from registration/randomization to death from any cause, assessed up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Event-free survival (EFS) (Cisplatin eligible cohort: Arms A and B)

Pathologic complete response (pCR) (Cisplatin ineligible cohort: Arm C)

Secondary study objectives

Cancer-specific survival (All Patients)

EFS (cisplatin-ineligible cohort: Arm C)

Incidence of adverse events (All Patients)

+3 more

Side effects data

From 2012 Phase 3 trial • 256 Patients • NCT01005680

51%

Neutropenia

47%

Leukopenia

46%

Nausea

43%

Vomiting

35%

Anaemia

31%

Decreased appetite

26%

Haemoglobin decreased

26%

Fatigue

25%

Constipation

25%

White blood cell count decreased

24%

Neutrophil count decreased

19%

Alanine aminotransferase increased

13%

Platelet count decreased

12%

Rash

10%

Aspartate aminotransferase increased

10%

Thrombocytopenia

Blood sodium decreased

Hypokalaemia

Insomnia

Pyrexia

Hyponatraemia

Blood creatinine increased

Lymphopenia

Diarrhoea

Dyspepsia

Red blood cell count decreased

Cough

Dizziness

Bone marrow failure

Dyspnoea

Cerebral infarction

Ischaemic stroke

Pulmonary embolism

Embolism venous

Superior vena cava syndrome

100%

80%

60%

40%

20%

Study treatment Arm

Gemcitabine Plus Cisplatin (GC)

Pemetrexed Plus Cisplatin (PC)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Arm C (durvalumab, gemcitabine hydrochloride)Experimental Treatment7 Interventions

Patients receive durvalumab IV over 60 minutes on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery. Patients also undergo tissue biopsy and blood sample collection on study, and CT or MRI throughout the trial.

Group II: Arm A (durvalumab, chemotherapy)Experimental Treatment11 Interventions

Patients receive durvalumab IV over 60 minutes on day 1 of chemotherapy cycles 1 and 3. Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery. Patients also undergo tissue biopsy and blood sample collection on study, and CT or MRI throughout the trial.

Group III: Arm B (chemotherapy)Active Control10 Interventions

Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery. Patients also undergo tissue biopsy and blood sample collection on study, and CT or MRI throughout the trial.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cisplatin

2013

Completed Phase 3

~3120

Pegfilgrastim

2013

Completed Phase 3

~4440