Trial record 1 of 1 for:
ea8191
Treating Prostate Cancer That Has Come Back After Surgery With Apalutamide and Targeted Radiation Using PET/CT Imaging
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| ClinicalTrials.gov Identifier: NCT04423211 |
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Recruitment Status :
Recruiting
First Posted : June 9, 2020
Last Update Posted : March 10, 2023
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Sponsor:
ECOG-ACRIN Cancer Research Group
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )
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Brief Summary:
This phase III trial compares the addition of apalutamide, with or without targeted radiation therapy, to standard of care treatment versus standard of care treatment alone in patients with prostate cancer biochemical recurrence (a rise in the blood level of prostate-specific antigen [PSA] after treatment with surgery or radiation). Diagnostic procedures, such as positron emission tomography/computed tomography (PET/CT), may help doctors look for cancer that has spread to the pelvis. Androgens can cause the growth of prostate cancer cells. Apalutamide may help fight prostate cancer by blocking the use of androgens by the tumor cells. Targeted radiation therapy uses high energy rays to kill tumor cells and shrink tumors that have spread. This trial may help doctors determine if using PET/CT results to deliver more tailored treatment (i.e., adding apalutamide, with or without targeted radiation therapy, to standard of care treatment) works better than standard of care treatment alone in patients with biochemical recurrence of prostate cancer.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Biochemically Recurrent Prostate Carcinoma Prostate Adenocarcinoma | Radiation: 3-Dimensional Conformal Radiation Therapy Drug: Apalutamide Procedure: Computed Tomography Radiation: External Beam Radiation Therapy Radiation: Fluciclovine F18 Drug: Goserelin Acetate Procedure: Intensity-Modulated Proton Therapy Radiation: Intensity-Modulated Radiation Therapy Drug: Leuprolide Acetate Procedure: Positron Emission Tomography Radiation: Stereotactic Body Radiation Therapy Radiation: Volume Modulated Arc Therapy | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 804 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase III Study of Local or Systemic Therapy INtensification DIrected by PET in Prostate CAncer Patients With Post-ProstaTEctomy Biochemical Recurrence (INDICATE). |
| Actual Study Start Date : | October 8, 2020 |
| Estimated Primary Completion Date : | December 31, 2032 |
| Estimated Study Completion Date : | December 31, 2032 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Prostate cancer
MedlinePlus related topics:
Prostate Cancer
Drug Information available for:
Apalutamide
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Arm A (EBRT, goserelin, leuprolide)
STEP 0: Patients receive fluciclovine F18 IV and undergo SOC PET/CT scan at baseline. STEP 1: Patients who are PET negative for extra pelvic metastases undergo SOC EBRT for 6 months. Patients also receive goserelin acetate SC or leuprolide acetate IM for 6 months starting up to 3 months prior to EBRT but no later than the first fraction of EBRT. All treatment continues for 6 months in the absence of disease progression or unacceptable toxicity. |
Procedure: Computed Tomography
Undergo PET/CT
Other Names:
Radiation: External Beam Radiation Therapy Undergo EBRT
Other Names:
Radiation: Fluciclovine F18 Given IV
Other Names:
Drug: Goserelin Acetate Given SC
Other Names:
Drug: Leuprolide Acetate Given IM
Other Names:
Procedure: Positron Emission Tomography Undergo PET/CT
Other Names:
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Experimental: Arm B (EBRT, goserelin, leuprolide, apalutamide)
STEP 0: Patients receive fluciclovine F18 IV and undergo SOC PET/CT scan at baseline. STEP 1: Patients who are PET negative for extra pelvic metastases undergo SOC EBRT and receive goserelin acetate SC or leuprolide acetate IM as in Arm A. Patients also receive apalutamide PO QD for 6 months in the absence of disease progression or unacceptable toxicity. |
Drug: Apalutamide
Given PO
Other Names:
Procedure: Computed Tomography Undergo PET/CT
Other Names:
Radiation: External Beam Radiation Therapy Undergo EBRT
Other Names:
Radiation: Fluciclovine F18 Given IV
Other Names:
Drug: Goserelin Acetate Given SC
Other Names:
Drug: Leuprolide Acetate Given IM
Other Names:
Procedure: Positron Emission Tomography Undergo PET/CT
Other Names:
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Experimental: Arm C (EBRT, goserelin, leuprolide, apalutamide)
STEP 0: Patients receive fluciclovine F18 IV and undergo SOC PET/CT scan at baseline. NOTE: Patients randomized to Arm C undergo a repeat fluciclovine F18 PET/CT at time of second PSA recurrence or 12 months after completion of enhanced systemic therapy. STEP 1: Patients who are PET positive for extra pelvic metastases undergo SOC EBRT and receive goserelin acetate SC or leuprolide acetate IM as in Arm A. Patients also receive apalutamide PO QD as in Arm B. |
Drug: Apalutamide
Given PO
Other Names:
Procedure: Computed Tomography Undergo PET/CT
Other Names:
Radiation: External Beam Radiation Therapy Undergo EBRT
Other Names:
Radiation: Fluciclovine F18 Given IV
Other Names:
Drug: Goserelin Acetate Given SC
Other Names:
Drug: Leuprolide Acetate Given IM
Other Names:
Procedure: Positron Emission Tomography Undergo PET/CT
Other Names:
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Experimental: Arm D (EBRT, goserelin, leuprolide, apalutamide, RT)
STEP 0: Patients receive fluciclovine F18 IV and undergo SOC PET/CT scan at baseline. NOTE: Patients randomized to Arm D undergo a repeat fluciclovine F18 PET/CT at time of second PSA recurrence or 12 months after completion of enhanced systemic therapy. STEP 1: Patients who are PET positive for extra pelvic metastases undergo SOC EBRT and receive goserelin acetate SC or leuprolide acetate IM as in Arm A and apalutamide PO QD as in Arm B. Patients also undergo SBRT or 3D CRT, IMRT (including VMAT), and IMPT over 3-5 fractions in the absence of disease progression or unacceptable toxicity. |
Radiation: 3-Dimensional Conformal Radiation Therapy
Undergo 3D CRT
Other Names:
Drug: Apalutamide Given PO
Other Names:
Procedure: Computed Tomography Undergo PET/CT
Other Names:
Radiation: External Beam Radiation Therapy Undergo EBRT
Other Names:
Radiation: Fluciclovine F18 Given IV
Other Names:
Drug: Goserelin Acetate Given SC
Other Names:
Procedure: Intensity-Modulated Proton Therapy Undergo IMPT
Other Name: IMPT Radiation: Intensity-Modulated Radiation Therapy Undergo IMRT
Other Names:
Drug: Leuprolide Acetate Given IM
Other Names:
Procedure: Positron Emission Tomography Undergo PET/CT
Other Names:
Radiation: Stereotactic Body Radiation Therapy Undergo SBRT
Other Names:
Radiation: Volume Modulated Arc Therapy Undergo VMAT
Other Name: VMAT |
Primary Outcome Measures :
- Progression-free survival (PFS) [ Time Frame: From randomization to radiographic progression by conventional imaging, symptomatic disease or death, whichever occurs first, assessed up to 10 years ]The power of the PFS analysis is 85% using one-sided 0.025 level stratified logrank test. The overall type I error will be controlled using an O'Brien-Fleming boundary function
- PFS prolongation in patients without positron emission tomography (PET)-evidence of extrapelvic metastases [ Time Frame: Up to 10 years ]Will evaluate whether the addition of enhanced systemic therapy to standard of care salvage therapy could prolong PFS in this patient population. Will be an intention-to-treat analysis of all randomized patients and performed in parallel with patients with PET-evidence of extrapelvic metastases.
- PFS prolongation in patients with PET-evidence of extrapelvic metastases [ Time Frame: Up to 10 years ]Will evaluate whether the addition of metastasis-directed radiation therapy to standard of care salvage therapy and enhanced systemic therapy could prolong PFS in this patient population. Will be an intention-to-treat analysis of all randomized patients and performed in parallel without patients with PET-evidence of extrapelvic metastases.
Secondary Outcome Measures :
- Overall survival (OS) [ Time Frame: From randomization to death or date last known alive, assessed up to 10 years ]Will be characterized by the method of Kaplan and Meier and a logrank test will be used to compare OS between the two arms in each cohort.
- Event-free survival [ Time Frame: From randomization to radiographic progression by conventional imaging, PET progression in the setting of rising PSA, symptomatic disease, initiation of new treatment for the disease or death, whichever occurs first, assessed up to 10 years ]Will be characterized by the method of Kaplan and Meier and a logrank test will be used to compare EFS between the two arms in each cohort.
- Time to prostate-specific antigen (PSA) progression [ Time Frame: From randomization to documented PSA progression or last disease assessment that shows free of PSA progression, assessed up to 10 years ]Will be characterized by the method of Kaplan and Meier and a logrank test will be used to compare time to PSA progression between the two arms in each cohort.
- Incidence of adverse events [ Time Frame: Up to 10 years ]Toxicity will be defined using the Common Terminology Criteria for Adverse Events.
- Detection rate of fluciclovine F18 (18F-fluciclovine) PET/computed tomography (CT) [ Time Frame: At time of PSA recurrence or 12 months after completion of enhanced systemic therapy (whichever occurs first), assessed up to 10 years ]For the detection rate, the proportion of baseline standard of care 18F-fluciclovine PET/CT (PET1) positive results at the patient and regional (prostate fossa, intrapelvic soft tissue/lymph node, extrapelvic soft tissue/lymph node, and bone metastases) level will be calculated and its 95% confidence interval will be estimated using the Exact method based on the binomial distribution.
- Concordance of detection rate with the follow-up conventional imaging modalities (CIM) [ Time Frame: At time of PSA recurrence or 12 months after completion of enhanced systemic therapy (whichever occurs first), assessed up to 10 years ]Will use Cohen's Kappa coefficient to measure the agreement between dichotomized PET/CT results and the dichotomized CIM results. Baseline CIM comparison will not be performed because as per our study eligibility criteria, baseline CIM will be negative for metastases.
- Distribution of 18F-fluciclovine PET-positive lesions among anatomic sites [ Time Frame: Baseline ]The rate of 18F-fluciclovine PET-positive lesions will be reported for each anatomic site, including prostate fossa, intrapelvic soft tissue/lymph node, extrapelvic soft tissue/lymph node, and bone metastases. Their confidence intervals will be estimated using the Exact method for the binomial distribution. To evaluate if PSA (level, doubling time, velocity) and other relevant clinical parameters affects the positivity distribution, will use the logistic regression to model with the binary outcome (positive vs. negative from PET/CT) and covariates will include anatomic site, PSA, and other clinical parameters. Will test the interactions between anatomic site and PSA (plus other clinical parameters) to see if the positivity distribution across anatomic site may change according to the levels of the interacted terms. Will use the technique of generalized estimating equation to account for the outcome correlations within subjects.
- Value of repeat PET to assess response to therapy compared to standard response assessments [ Time Frame: At time of PSA recurrence or 12 months after completion of enhanced systemic therapy (whichever occurs first), assessed up to 10 years ]Analyses will be conducted to evaluate qualitative visual evidence of 18F-fluciclovine PET positive metastatic lesions and quantitative PET standardized-uptake value (SUV) changes on a lesion-to-lesion basis from 18F-fluciclovine PET1 (baseline) to PET2 on visually determined sites of recurrence and metastatic disease. This will be compared to reference standard-of-care conventional imaging (Prostate Cancer Working Group 2 criteria) and PSA response at PET2 time point to determine PET2 response to therapy. PET2 visual and quantitative assessment will also be compared to PFS in the time-to-event analysis using a log-rank test (PET2 visual assessment) and a Cox proportional hazards regression (PET2 quantitative assessment). PET SUV parameters to be obtained at PET1 and PET2 will include SUVmax, SUVpeak. PET SUV change from PET1 to PET2 will include absolute SUVmax and SUVpeak change (PET2-PET1) and percent change of SUVmax and SUVpeak (% change = 100*[(PET2-PET1)/PET1]).)
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- STEP 0: REGISTRATION ELIGIBILITY CRITERIA
- Patient must have had a radical prostatectomy (RP) as definitive therapy for histopathologically-proven prostatic adenocarcinoma
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Patient must have biochemical recurrence (BCR) after RP, with rising PSA defined as follows:
- If time to biochemical recurrence, (defined as time to first detectable PSA after RP) is < 12 months, a minimum PSA level of >= 0.2 ng/mL and a confirmatory reading of >= 0.2 ng/mL is required, per the American Urological Association (AUA) definition (this includes patients with a persistent PSA reading of at least 0.2 ng/mL)
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If time to biochemical recurrence, (defined as time to first detectable PSA after RP) is >= 12 months, a minimum absolute PSA of 0.5 ng/mL is required
- NOTE: Qualifying PSA values per above must be collected at least 4 weeks after RP, with confirmatory persistent or elevated PSA collected at any subsequent time point
- Patient must be negative or equivocal for extrapelvic metastatic disease by conventional imaging modalities (CIM) (i.e., bone scans, pelvic CT, or pelvic MRI), which must be done within 10-12 weeks prior to registration. Extra-pelvic metastases is defined as any osseous metastases and/or any extrapelvic soft tissue, lymph nodes and organ metastases; extra-pelvic is defined as superior to common iliac bifurcation, outside of standard prostate bed + whole pelvis nodal RT fields
- Baseline PET/CT scan (PET1) are eligible for this study if the SOC PET scan using 18F-fluciclovine (Axumin) is completed during step 0 registration or up to 12 weeks prior to step 0 registration. The PET/CT scanners must meet scanner qualifications and scans must have an interpretation (or confirmation of an institutional clinical read) by a nuclear medicine physician or radiologist who has undergone 18F-fluciclovine (Axumin) reader training
- Patient must be a candidate for standard-of-care (SOC) post-prostatectomy radiation therapy (RT) to the prostate bed and pelvic nodes with androgen deprivation therapy (adjuvant)
- Patient must have the ability to provide written informed consent
- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Patient must be able to lie flat and still for approximately 20-30 minutes or otherwise tolerate a PET/CT scan and radiation treatment planning and delivery
- Patient must be at a participating institution, which has agreed to perform the imaging research studies, completed the ECOG-American College of Radiology Imaging Network (ACRIN) defined PET/CT scanner qualification procedures and received ECOG-ACRIN PET/CT scanner approval
- Leukocytes >= 3,000/mcL (obtained within 4 weeks prior to registration)
- Absolute neutrophil count >= 1,500/mcL (obtained within 4 weeks prior to registration)
- Platelets >= 100,000/mcL (obtained within 4 weeks prior to registration)
- Total bilirubin =< institutional upper limit of normal (ULN) (obtained within 4 weeks prior to registration)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained within 4 weeks prior to registration)
- Glomerular filtration rate (GFR) > 35 mL/min estimated by Cockcroft-Gault or measured directly by 24 hour urine creatinine (obtained within 4 weeks prior to registration)
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- 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
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class I or II (by patient symptoms) or A or B (by objective assessment)
- STEP 1: RANDOMIZATION ELIGIBILITY CRITERIA
- Patient must have completed a baseline SOC PET scan (PET1) with results of extra-pelvic metastases involvement known (positive or negative)
- For patients with negative extra-pelvic metastases, PET-imaging status of intra-pelvic nodes must be known (positive or negative)
- For patients with positive extra-pelvic metastases (defined as any PET positive lesions outside of standard salvage RT fields [prostate bed +/- typical whole pelvis]), the number of extra-pelvic lesions must be known (=< 5 or > 5 pelvic lesions)
Exclusion Criteria:
- Patient must not have started androgen deprivation therapy for biochemical recurrence prior to baseline study PET/CT imaging
- Patient must not be enrolled in another therapeutic clinical trial
- Patient must not have any other malignancy within the last 2 years, other than superficial bladder cancer and skin basal cell carcinoma or cutaneous superficial squamous cell carcinoma that has not metastasized
- Patient must not have history of seizures or known condition that may cause predisposal to seizures (e.g., stroke or head trauma resulting in loss of consciousness) within 1 year of registration
- Patient must not have history of inflammatory bowel disease as this would increase risk of complication from radiotherapy or any gastrointestinal disorder affecting absorption
- Patient must not have had prior radiation therapy
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04423211
Locations
Show 86 study locations
Sponsors and Collaborators
ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Neha Vapiwala | ECOG-ACRIN Cancer Research Group |
| Responsible Party: | ECOG-ACRIN Cancer Research Group |
| ClinicalTrials.gov Identifier: | NCT04423211 |
| Other Study ID Numbers: |
EA8191 NCI-2020-02686 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) EA8191 ( Other Identifier: ECOG-ACRIN Cancer Research Group ) EA8191 ( Other Identifier: CTEP ) U10CA180820 ( U.S. NIH Grant/Contract ) |
| First Posted: | June 9, 2020 Key Record Dates |
| Last Update Posted: | March 10, 2023 |
| Last Verified: | March 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
Additional relevant MeSH terms:
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Prostatic Neoplasms Adenocarcinoma Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms Genital Diseases, Male Genital Diseases Urogenital Diseases Prostatic Diseases Male Urogenital Diseases |
Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Leuprolide Goserelin Fertility Agents, Female Fertility Agents Reproductive Control Agents Physiological Effects of Drugs Antineoplastic Agents, Hormonal Antineoplastic Agents |