Prostate Cancer
NRG-GU010: Two Studies for Patients With Unfavorable Intermediate Risk Prostate Cancer Testing Less Intense Treatment for Patients With a Low Gene Risk Score and Testing a More Intense Treatment for Patients With a Higher Gene Risk Score
Description
This phase III trial uses the Decipher risk score to guide intensification (for higher Decipher gene risk) or de-intensification (for low Decipher gene risk) of treatment to better match therapies to an individual patient's cancer aggressiveness. The Decipher risk score evaluates a prostate cancer tumor for its potential for spreading. In patients with low risk scores, this trial compares radiation therapy alone to the usual treatment of radiation therapy and hormone therapy (androgen deprivation therapy). Radiation therapy uses high energy x-rays or particles to kill tumor cells and shrink tumors. Androgen deprivation therapy blocks the production or interferes with the action of male sex hormones such as testosterone, which plays a role in prostate cancer development. Giving radiation treatment alone may be the same as the usual approach in controlling the cancer and preventing it from spreading, while avoiding the side effects associated with hormonal therapy. In patients with higher Decipher gene risk, this trial compares the addition of darolutamide to usual treatment radiation therapy and hormone therapy, to usual treatment. Darolutamide blocks the actions of the androgens (e.g. testosterone) in the tumor cells and in the body. The addition of darolutamide to the usual treatment may better control the cancer and prevent it from spreading.
Inclusion Notes
For a full description of this trial, please go to the listing on www.clinicaltrials.gov
Eligibility Criteria
Inclusion Criteria:
Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of the prostate by biopsy, with most recent biopsy (if multiple) within 365 days prior to registration;
Unfavorable intermediate risk prostate cancer, defined as having ALL the following bulleted criteria:
Has at least one intermediate risk factor (IRF):
PSA 10-20 ng/mL
Clinical stage T2b-c (DRE and/or imaging) by American Joint Committee on Cancer (AJCC) 8th edition
Gleason Score 7 (Gleason 3+4 or 4+3 [ISUP Grade Group 2-3])
Has ONE or more of the following ‘unfavorable’ intermediate-risk designators:
>1 IRF - Gleason 4+3=7 (ISUP Grade Group 3)
≥50% of biopsy cores positive*
Absence of high-risk features, see section 3.2.11
*Biopsies may include 'sextant' sampling of right/left regions of the prostate, often labeled base, mid-gland and apex. All such 'sextant' biopsy cores should be counted. Men may also undergo 'targeted' sampling of prostate lesions (guided by MRI, ultrasound or other approaches). A targeted lesion that is biopsied more than once and demonstrates cancer (regardless of number of targeted cores involved) should count as a single additional positive core sampled and positive. In cases of uncertainty, count the biopsy sampling as sextant core(s).
Appropriate stage for study entry based on the following diagnostic workup:
History/physical examination within 120 days prior to registration;
Negative bone imaging (M0) within 180 days prior to registration;
Note: Tc-99m bone scan or NaF positron emission tomography (PET) are allowed. Equivocal bone scan findings are allowed if plain films X-ray, CT or magnetic resonance imaging (MRI) are negative for metastasis at the concerned site(s). While a negative fluciclovine, choline, or prostate specific membrane antigen (PSMA) PET may be counted as acceptable substitute for bone imaging, any suspicious findings must be confirmed and correlated with conventional imaging (Tc-99m bone scan, NaF PET, CT, X-ray, or MRI) to determine eligibility based on the latter modalities (e.g. M0 based on conventional imaging modalities).
Clinically negative lymph nodes (N0) as established by conventional imaging (pelvic +/- abdominal CT or MR), within 180 days prior to registration. Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are ≤ 1.0 cm in short axis and/or if biopsy is negative.
Note: While a negative fluciclovine, choline, or prostate specific membrane antigen (PSMA) PET may be counted as acceptable substitute for pelvic imaging, any suspicious findings must be confirmed by conventional imaging (CT, MRI or biopsy). If the findings do not meet pathological criteria based on the latter modalities (e.g. node <=10mm in short axis, negative biopsy), the patient will still be eligible.
Age ≥ 18; 3.1.5 ECOG Performance Status of 0-2 within 120 days prior to registration;
Non-castrate testosterone level (>50ng/dL) within 120 days prior to registration;
Adequate hematologic function within 120 days prior to registration defined as follows:
Absolute Neutrophil > 1,000 cells/mm3
Hemoglobin > 8.0 g/dL, independent of transfusion and/or growth factors
Platelet count ≥ 100,000 cells/mm3 independent of transfusion and/or growth factors
Adequate renal function within 120 days prior to registration defined as follows:
Creatinine Clearance (CrCl) ≥30 mL/min estimated by Cockcroft-Gault Equation:
CrCl (mL/min) = [140 – age (years)] x weight (kg) / 72 x serum creatinine (mg / dL)
For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR≥30 mL/min/1.73m2 will be considered adequate:
GFR = 141 × min(Scr/κ, 1)-0.411 × max(Scr/κ, 1)-1.209 × 0.993Age × 1.159 [if patient identifies as African American]
where:
Scr is serum creatinine in mg/dL,
κ is 0.9 for males,
min indicates the minimum of Scr/κ or 1, and
max indicates the maximum of Scr/κ or 1
A calculator for this formula is available at: https://www.niddk.nih.gov/health-information/professionals/clinical-tools-patient-management/kidney-disease/laboratory-evaluation/glomerular-filtration-rate-calculators/ckd-epi-adults-conventional-units
Adequate hepatic function within 120 days prior to registration defined as follows:
Total Bilirubin: 1.5 ≤ institutional upper limit of normal (ULN) (Note: In subjects with Gilbert’s syndrome, if total bilirubin is >1.5 x ULN, measure direct and indirect bilirubin. If direct bilirubin is less than or equal to 1.5 x ULN, subject is eligible).
AST(SGOT) and ALT(SGPT): ≤ 2.5 × institutional ULN
HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial; Note: HIV testing is not required for eligibility for this protocol.
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B).
For patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy.
The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information
Start Date
Tuesday, November 1, 2022
Principal / Contact Name
John A. Pablo, MD