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Trial record 1 of 1 for:    PSMAfore
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177Lu-PSMA-617 vs. Androgen Receptor-directed Therapy in the Treatment of Progressive Metastatic Castrate Resistant Prostate Cancer (PSMAfore)

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ClinicalTrials.gov Identifier: NCT04689828
Recruitment Status : Recruiting
First Posted : December 30, 2020
Last Update Posted : December 2, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

The purpose of this study is to determine whether 177Lu-PSMA-617 improves the rPFS or death compared to a change in ARDT in mCRPC participants that were previously treated with an alternate ARDT and not exposed to a taxane-containing regimen in the CRPC or mHSPC settings.

Approximately 450 participants will be randomized (225 per treatment group).


Condition or disease Intervention/treatment Phase
Prostatic Neoplasms Radiation: 177Lu-PSMA-617 Radiation: 68Ga-PSMA-11 Drug: ARDT Other: Best supportive care Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients randomized to ARDT treatment have an option to crossover to 177Lu-PSMA-617 treatment after rPFS.
Masking: Single (Outcomes Assessor)
Masking Description: No masking.
Primary Purpose: Treatment
Official Title: PSMAfore: A Phase III, Open-label, Multi-Center, Randomized Study Comparing 177Lu-PSMA-617 vs. a Change of Androgen Receptor-directed Therapy in the Treatment of Taxane Naïve Men With Progressive Metastatic Castrate Resistant Prostate Cancer
Actual Study Start Date : June 15, 2021
Estimated Primary Completion Date : August 26, 2022
Estimated Study Completion Date : April 27, 2023


Arm Intervention/treatment
Experimental: 177Lu-PSMA-617
Participants will receive 7.4 GBq (200 mCi) +/- 10% 177Lu-PSMA-617 once every 6 weeks for 6 cycles. Best supportive care, including ADT may be used.
Radiation: 177Lu-PSMA-617
administered intravenously once every 6 weeks (1 cycle) for 6 cycles

Radiation: 68Ga-PSMA-11
single intravenous dose of approximately 150 MBq. Administered dose must not be lower than 111 MBq or higher than 185 MBq (3 - 5 mCi).

Other: Best supportive care
Best supportive/best standard of care as defined by the local investigator

Active Comparator: Androgen receptor-directed therapy (ARDT)
For participants randomized to the ARDT arm, the change of ARDT treatment will be administered per the physician's orders. Best supportive care, including ADT may be used.
Radiation: 68Ga-PSMA-11
single intravenous dose of approximately 150 MBq. Administered dose must not be lower than 111 MBq or higher than 185 MBq (3 - 5 mCi).

Drug: ARDT
administered orally on a continuous basis, as per package insert and guidelines
Other Name: Comparator

Other: Best supportive care
Best supportive/best standard of care as defined by the local investigator




Primary Outcome Measures :
  1. Radiographic Progression Free Survival (rPFS) [ Time Frame: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 43 months (estimated final OS analysis) ]
    rPFS is defined as the time to radiographic progression by PCWG3-modified RECIST v1.1 (as assessed by Blinded independent central review) or death.


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: From date of randomization until date of death from any cause, assessed up to 43 months (estimated final OS analysis) ]
    OS is defined as time to death for any cause

  2. Radiographic Progression Survival 2 (rPFS2) [ Time Frame: Only for participants that crossover from ARDT arm to Lu-PSMA treatment. From date of crossover until second radiographic progression or death, whichever comes first, assessed up to 43 months (estimated final OS analysis) ]
    rPFS2 is defined as time from the date of crossover (ARDT to 177Lu-PSMA-617) to the date of radiographic disease progression by BICR or death from any cause

  3. Progression free survival (PFS) [ Time Frame: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up to 43 months (estimated final OS analysis) ]
    PFS is defined as time from date of randomization to the first documented progression by investigator's assessment (radiographic, clinical, or PSA progression) or death from any cause, whichever occurs first

  4. Second Progression Free Survival (PFS2) by investigator's assessment [ Time Frame: From date of randomization until date of second progression or date of death from any cause, whichever comes first, assessed up to 43 months (estimated final OS analysis) ]
    PFS2 defined as time from date of randomization to the first documented progression by investigator's assessment (radiographic progression, clinical progression, PSA progression) or death from any cause, whichever occurs first, on next-line of therapy

  5. Biochemical response [ Time Frame: From date of randomization till 30 day safety follow-up, assessed up to 43 months (estimated final OS analysis) ]

    PSA50 defined as proportion of participants who achieved a ≥ 50% decrease from baseline that is confirmed by a second PSA measurement ≥ 4 weeks.

    PSA50 will be evaluated at 3, 6 and 12 months.


  6. Time to First Symptomatic Skeletal Event (TTSE) [ Time Frame: From date of randomization till EOT or death, whichever happens first, assessed up to 43 months (estimated final OS analysis) ]
    Time to SSE (TTSSE) defined as date of randomization to the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death from any cause, whichever occurs first

  7. Time to radiographic soft tissue progression (TTSTP) [ Time Frame: From date of randomization until date of soft tissue radiographic progression or date of death from any cause, whichever comes first, assessed up to 43 months (estimated final OS analysis) ]
    TTSTP defined as time from randomization to radiographic soft tissue progression per PCWG3-modified RECIST v1.1 (Soft Tissue Rules of Prostate Cancer Working Group modified Response Evaluation Criteria in Solid Tumors Version 1.1) as Assessed by Blinded Independent Central Review (BICR)

  8. Time to chemotherapy (TTCT) [ Time Frame: From date of randomization until date of subsequent chemotherapy or date of death from any cause, whichever comes first, assessed up to 43 months (estimated final OS analysis) ]
    TTCT defined as time from randomization to initiation of the first subsequent chemotherapy or death, whichever occurs first

  9. European Quality of Life (EuroQol) - 5 Domain 5 Level scale (EQ-5D- 5L) [ Time Frame: From randomization up till 30 day safety Follow-up or week 48 of long term Follow-up for patients prematurely discontinued, assessed up to 43 months (estimated final OS analysis) ]
    EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Higher scores indicated greater levels of problems across each of the five dimensions.

  10. Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire [ Time Frame: From randomization up till 30 day safety Follow-up or week 48 of long term Follow-up for patients prematurely discontinued, assessed up to 43 months (estimated final OS analysis) ]
    FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT- General + the Prostate Cancer Subscale (PCS). The FACTGeneral (FACT-G) is a 27 item Quality of Life (QoL) measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), and Emotional Well-being (0-24). The total score range is between 1-108, higher scores indicates better for total score and subscale scores. PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48, higher scores better). The FACT-P total score is the sum of all 5 subscale scores of the FACT-P questionnaire and ranges from 0-156. Higher scores indicate higher degree of functioning and better quality of life.

  11. Brief Pain Inventory - Short Form (BPI-SF) Questionnaire [ Time Frame: From screening up till 30 day safety Follow-up or week 48 of long term Follow-up for patients prematurely discontinued, assessed up to 43 months (estimated final OS analysis) ]
    The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item selfreport questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain severity score is a mean value for BPI-SF questions 3, 4, 5 and 6 (questions inquiring about the extent of pain, where the extent is ranked from 0 [no pain] to 10 [pain as bad as you can imagine]). Pain severity progression is defined as an increase in score of 30% or greater from baseline without decrease in analgesic use.

  12. Number of Participants with Treatment Emergent Adverse Events [ Time Frame: From randomization till 30 day safety follow-up, assessed up to 43 months (estimated final OS analysis) ]
    The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Prostate cancer study.
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

  1. Signed informed consent must be obtained prior to participation in the study
  2. Participants must be adults ≥ 18 years of age
  3. Participants must have an ECOG performance status of 0 to 1
  4. Participants must have histological pathological, and/or cytological confirmation of adenocarcinoma of the prostate
  5. Participants must be 68Ga-PSMA-11 PET/CT scan positive, and eligible as determined by the sponsor's central reader
  6. Participants must have a castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L)
  7. Participants must have received one prior approved ARDT (for example, abiraterone, enzalutamide, darolutamide, or apalutamide, etc.) and have documented progression on therapy
  8. Participants must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria:

    • Serum/plasma PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL
    • Soft-tissue progression defined [PCWG3-modified RECIST v1.1 (Eisenhauer et al 2009, Scher et al 2016)]
    • Progression of bone disease: evaluable disease or one or more new bone lesions(s) by bone scan (PCWG3 criteria (Scher et al 2016))
  9. Participants must have ≥ 1 metastatic lesion that is present on screening/baseline CT, MRI, or bone scan imaging obtained ≤ 28 days prior to beginning study therapy
  10. Participants must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies (i.e. prior chemotherapy, radiation, etc.) except alopecia
  11. Participants must have adequate organ function:

    • Bone marrow reserve:
    • ANC ≥ 1.5 x 109/L
    • Platelets ≥100 x 109/L
    • Hemoglobin ≥ 9 g/dL
    • Hepatic:
    • Total bilirubin < 2 x the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤ 3 x ULN is permitted
    • ALT or AST ≤ 3.0 x ULN OR ≤ 5.0 x ULN for participants with liver metastases
    • Renal:
    • eGFR ≥ 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation
  12. Albumin ≥ 2.5 g/dL
  13. Candidates for change in ARDT as assessed by the treating physician

Exclusion Criteria:

Participants meeting any of the following criteria are not eligible for inclusion in this study:

  1. Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation
  2. Previous PSMA-targeted radioligand therapy
  3. Prior treatment with cytotoxic chemotherapy for castration resistant or castrate sensitive prostate cancer (e.g., taxanes, platinum, estramustine, vincristine, methotrexate, etc.), immunotherapy or biological therapy [including monoclonal antibodies]) [Note: Taxane exposure (maximum 6 cycles) in the adjuvant or neoadjuvant setting is allowed if 12 months have elapsed since completion of this adjuvant or neoadjuvant therapy]
  4. Any investigational agents within 28 days prior to day of randomization
  5. Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar classes
  6. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy
  7. Transfusion or use of bone marrow stimulating agents for the sole purpose of making a participant eligible for study inclusion
  8. Patients with a history of CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with CNS metastases are eligible if received therapy (surgery, radiotherapy, gamma knife), asymptomatic and neurologically stable without corticosteroids. Participants with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired.
  9. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
  10. History or current diagnosis of the following ECG abnormalities indicating significant risk of safety for study participants:

    • Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block)
    • History of familial long QT syndrome or known family history of Torsades de Pointe
    • Cardiac or cardiac repolarization abnormality, including any of the following: History of myocardial infarction (MI), angina pectoris, or CABG within 6 months prior to starting study treatment
  11. Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation

    • HIV-infected participants who are at a low risk of AIDS-related outcomes may participate in this trial.
    • Participants with an active documented COVID-19 infection (any grade of disease severity) at time of informed consent may be included only when completely recovered (in accordance with local guidance) and had no symptoms for at least 28 days before the first dose of study medication.
  12. Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. Participants with a prior history of malignancy that has been adequately treated and who have been disease free for more than 3 years are eligible, as are participants with adequately treated non-melanoma skin cancer, superficial bladder cancer
  13. Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 6 months after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF
  14. Concurrent bladder outflow obstruction or unmanageable urinary incontinence
  15. History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study
  16. Any condition that precludes raised arms position
  17. Presence of any mutations or biomarkers that are known as predictors of better response to treatments other than ARDT (e.g., AR-V7 or BRCA) as assessed by the investigator
  18. Not able to understand and to comply with study instructions and requirements

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): NCT04689828


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04689828    
Other Study ID Numbers: CAAA617B12302
2020-003969-19 ( EudraCT Number )
First Posted: December 30, 2020    Key Record Dates
Last Update Posted: December 2, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
177Lu-PSMA-617
Androgen receptor-directed therapy
ARDT
Metastatic castrate resistant prostate cancer
mCRPC
Radiographic progression free survival
rPFS
Castrate resistant prostate cancer
CRPC
Hormone sensitive prostate cancer
HSPC
Prostate-specific membrane antigen
PSMA
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Gallium 68 PSMA-11
177Lu-PSMA-617
Radiopharmaceuticals
Molecular Mechanisms of Pharmacological Action