An Open-label Study Comparing Lutetium (177Lu) Vipivotide Tetraxetan Versus Observation in PSMA Positive OMPC.

NCT05939414 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CAAA617D123022022-502956-29-00
• Study Type: interventional
• Target: 450
• Locations: 25 countries
• Sites: 138

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of lutetium (177Lu) vipivotide tetraxetan (AAA617) in participants with oligometastatic prostate cancer (OMPC) progressing after definitive therapy to their primary tumor. The data generated from this study will provide evidence for the treatment of AAA617 in early-stage prostate cancer patients to control recurrent tumor from progressing to fatal metastatic disease while preserving quality of life by delaying treatment with androgen deprivation therapy (ADT).

Conditions

Oligometastatic Prostate Cancer (OMPC)

Keywords

Lutetium (177Lu) vipivotide tetraxetan; Oligometastatic Prostate Cancer (OMPC); Metastasis Free Survival (MFS); gallium (68Ga) gozetotide; piflufolastat (18F); prostate-specific membrane antigen (PSMA); Delay Castration; Stereotactic Body Radiation Therapy (SBRT); metastasis-directed therapy; Androgen Deprivation Therapy (ADT)-free survival.

Outcome Measures

Primary Outcomes (1)

• Blinded Independent Review Committee (BIRC) assessed Metastasis Free Survival (MFS)

  Blinded Independent Review Committee (BIRC) assessed Metastasis Free Survival (MFS) is defined as the time from randomization to first evidence of radiographically detectable bone or soft tissue distant metastasis by conventional imaging (i.e., Computed Tomography (CT)/Magnetic Resonance Imaging (MRI) and bone scans) as assessed by BIRC using RECIST 1.1 or death due to any cause, whichever occurs first. Participants who are alive without distant metastasis at the analysis data cut-off or are lost to follow-up at the time of analysis will be censored for MFS at the time of their last adequate radiographic assessment. Clinical deterioration without objective radiographic evidence will not be considered as documented distant metastasis.

  From date of randomization until first evidence of radiographically detectable bone or soft tissue distant metastasis or death due to any cause, whichever occurs first, assessed up to approximately 30 months

Secondary Outcomes (15)

• Key secondary endpoint: Time to Hormonal Therapy (TTHT)

  From date of randomization until date of Androgen Deprivation Therapy (ADT), assessed up to approximately 74 months

• Investigator assessed Metastasis Free Survival (MFS)

  From date of randomization until first evidence of radiographically detectable bone or soft tissue distant metastasis or death from any cause, whichever occurs first, assessed up to approximately 74 months

• Time to prostate specific antigen (PSA) progression (TTPSAP)

  From date of randomization until date of first PSA progression, assessed up to approximately 74 months

• Radiographic Progression Free Survival (rPFS)

  From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 74 months

• Time to next therapy (local or systemic)

  From date of randomization until initiation of the next line of therapy (local or systemic), assessed up to approximately 74 months

Study Arms (2)

Investigational Arm: lutetium (177Lu) vipivotide tetraxetan (AAA617)

EXPERIMENTAL

All participants will be treated with Stereotactic Body Radiation Therapy (SBRT) to all metastatic lesions followed by a dose of 7.4 GBq (200 mCi) +/- 10% of AAA617 which will be administered once every 6 weeks (1 cycle) for a planned 4 cycles.

Drug: AAA617

Control arm: observation (watchful waiting)

NO INTERVENTION

All participants will be treated with Stereotactic Body Radiation Therapy (SBRT) to all metastatic lesions followed by observation only.

Interventions

AAA617 DRUG

Stereotactic Body Radiation Therapy (SBRT) followed by AAA617 will be administered once every 6 weeks (1 cycle) for a planned 4 cycles to participants randomized to the Investigational arm

Also known as: (177Lu) vipivotide tetraxetan

Investigational Arm: lutetium (177Lu) vipivotide tetraxetan (AAA617)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed prostate cancer prior to randomization
• Participants must have biochemically recurrent disease after definitive treatment to prostate by Radical Prostatectomy ((RP), (alone or with post-operative radiation to prostate bed/pelvic nodes)) or External beam Radiation Therapy (EBRT), (prostate alone or prostate with seminal vesicle and/or pelvic nodes) and/or brachytherapy prior to randomization. Biochemical recurrence (BCR) is defined as: nadir PSA + 2 ng/mL post XRT (if participant received-radiation therapy to intact prostate) and PSA \> 0.2 ng/mL and rising post RP (with or without post-operation Radiation Therapy (RT))
• Participants must have OMPC with 1-5 PSMA -positive metastatic lesions on screening PSMA PET/CT scan (with either gallium (68Ga) gozetotide or piflufolastat (18F)) as visually assessed by BIRC. For definition of PSMA PET positivity, please refer to Section 8.1 and the Imaging Manual. Metastatic lesions may include regional/pelvic lymph nodes (N1), distant lymph nodes (M1a), bone (M1b), lung and others visceral (M1c) except liver and brain classified using American Joint Committee on Cancer (AJCC) 8. When counting the number of oligometastatic lesions, each lesion is counted as distinct metastasis irrespective of its anatomical location (e.g., one pelvic and one extra-pelvic lymph node will be counted as two metastatic lesions)
• At least 1 PSMA-positive lesion must be a distant metastasis (M1) per AJCC8 classification at screening. For AJCC M staging, PSMA PET/CT information should be used
• Participants must have a negative CI for M1 disease at screening.
• Note:
• For a participant not to be eligible, CI positive M1 lesions should be unequivocal in CI scans, i.e., potentially not attributable to findings thought to represent something other than tumor (e.g., degenerative, or post-traumatic changes or Paget's disease in bone lesions). For CI assessments, bone lesions must be assessed by bone scan only and soft tissue lesions must be assessed by CT/MRI scans only at screening.
• Prior knowledge of PSMA PET positivity should not influence the radiologist (reader) in determination of CI positivity. Two different readers will be involved, one reader for PSMA PET/CT scan and one reader for CI: Reader will be blinded to PSMA PET scan results while reading CI scans. Reader should not modify their assessment of CI scans (e.g. changing a lesion previously identified as equivocal in CI to unequivocal) after reading the PSMA PET scan. Similarly, biopsy positivity should not influence the reader in the assessment of CI positivity. More details on the reading paradigm will be provided in the imaging charter
• MRI for radiation treatment planning may show M1 disease but this will not exclude the participant from the study if the lesion is deemed negative per baseline CT or bone scans
• Participants with pelvic disease (N1) seen in CI are allowed if the local spread is below common iliac bifurcation (per AJCC 8 definition of local disease)
• If a previously surgically removed lesion was unequivocal for M1 by bone scan or CT, the participant is not eligible.
• All metastatic lesions detected at screening must be amenable to SBRT
• Non-castration testosterone level \>100 ng/dL at screening

You may not qualify if:

• Participants with de novo OMPC at screening
• Unmanageable concurrent bladder outflow obstruction or urinary incontinence at screening. Note: participants with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (incl. pads, drainage) are allowed
• Prior therapy with:
• ADT (including bilateral orchiectomy) and ARPIs used for metastatic prostate cancer treatment
• Participants who received AR-directed therapy, whether ADT or an ARPI or both, as neoadjuvant or adjuvant therapy as a component of their primary therapy, are eligible provided that they discontinued therapy ≥12 months prior to randomization for ADT (i.e., 12 months after the last day of the last injection) or ≥3 months if ARPI was given as monotherapy. ARPI's as a term includes both contemporary androgen synthesis inhibitors (e.g., abiraterone, galeterone, and orteneronel), and receptor inhibitors (enzalutamide, apalutamide and darolutamide).
• Patients who biochemically relapsed after primary therapy may also have had treatment with AR directed therapy and participants who had SBRT with ADT are also eligible provided that the ARPI +/- ADT or ADT alone was terminated
• ≥12 months prior to randomization for ADT (i.e., 12 months after the last day of the last injection) or ≥3 months if ARPI was given as monotherapy.
• Participants who received first generation anti-androgens (bicalutamide, flutamide, nilutamide, cyproterone) for biochemical recurrence or adjuvant/neoadjuvant therapy are eligible provided that they discontinued therapy ≥3 months prior to randomization.
• Participants who have discontinued ADT due to disease progression are not eligible (i.e., Castration-Resistant Prostate Cancer (CRPC) participants)
• Other hormonal therapy. e.g.,
• Use of estrogens, 5-α reductase inhibitors (finasteride, dutasteride), other steroidogenesis inhibitors (aminoglutethimide) if used in the context of prostate cancer treatment. Same medications are allowed if used for other indications: e.g., Benign Prostatic Hyperplasia (BPH), if stopped ≥3 months before randomization.
• Radiopharmaceutical agents (e.g., Strontium-89, PSMA-targeted radioligand therapy)
• Immunotherapy (e.g., sipuleucel-T)
• Chemotherapy, except if administered in the adjuvant/neoadjuvant setting completed \> 12 months before randomization
• Any other investigational or systemic agents for metastatic disease

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (142)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

RECRUITING

VA Greater LA Healthcare System

Los Angeles, California, 90073, United States

RECRUITING

VA Palo Alto Health Care System

Palo Alto, California, 94304-1207, United States

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Stanford University

Palo Alto, California, 94304, United States

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UCSF

San Francisco, California, 94115, United States

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Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

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Cancer Specialists of North Florida

Jacksonville, Florida, 32256, United States

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Woodlands Medical Specialists

Pensacola, Florida, 32503, United States

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Piedmont Healthcare

Atlanta, Georgia, 30318, United States

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University of Chicago

Chicago, Illinois, 60637, United States

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The Cancer Institute of Alexian Brothers

Elk Grove, Illinois, 60007, United States

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Unity Point Clinic

Des Moines, Iowa, 50323, United States

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University of Kansas Hospital

Kansas City, Kansas, 66160, United States

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Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, 70809, United States

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East Jefferson Hospital

Metairie, Louisiana, 70006, United States

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University of Maryland Medical Ctr

Baltimore, Maryland, 21201, United States

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Johns Hopkins Kimmel Com Cancer Ctr

Baltimore, Maryland, 21231, United States

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Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

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Beth Israel Deaconess Med Ctr

Boston, Massachusetts, 02215, United States

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BAMF Health

Grand Rapids, Michigan, 49503, United States

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Profound Research LLC

Royal Oak, Michigan, 48073, United States

ACTIVE NOT RECRUITING

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

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Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

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VA St Louis Health Care System

St Louis, Missouri, 63106, United States

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Wash U School of Medicine

St Louis, Missouri, 63110, United States

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The Urology Center PC DBA UroHealth Partners

Omaha, Nebraska, 68114, United States

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Memorial Sloan Kettering Cancer Ctr

New York, New York, 10065, United States

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Associated Med Professionals of NY

Syracuse, New York, 13210, United States

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Montefiore Hospital

The Bronx, New York, 10467 2490, United States

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East Carolina University

Greenville, North Carolina, 27858, United States

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Dayton Physicians

Kettering, Ohio, 45409, United States

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Oregon Urology Institute

Springfield, Oregon, 97477, United States

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Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

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Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

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Univ of Texas Southwest Med Center

Dallas, Texas, 75390-9034, United States

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Rio Grande Urology

El Paso, Texas, 79912, United States

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Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

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Blue Ridge Cancer Center

Wytheville, Virginia, 24382, United States

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Novartis Investigative Site

CABA, Buenos Aires, C1426ANZ, Argentina

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Novartis Investigative Site

CABA, C1181ACH, Argentina

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Novartis Investigative Site

Caba, C1431FWO, Argentina

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Novartis Investigative Site

Darlinghurst, New South Wales, 2010, Australia

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Novartis Investigative Site

Herston, Queensland, 4029, Australia

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Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

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Novartis Investigative Site

Malvern, Victoria, 3144, Australia

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Novartis Investigative Site

Linz, 4020, Austria

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Vienna, 1090, Austria

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Aalst, 9300, Belgium

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Novartis Investigative Site

Ghent, 9000, Belgium

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Novartis Investigative Site

Wilrijk, 2610, Belgium

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Novartis Investigative Site

São Paulo, São Paulo, 01246 000, Brazil

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Calgary, Alberta, T2N 5G2, Canada

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Halifax, Nova Scotia, B3H 2Y9, Canada

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London, Ontario, N6A 4G5, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Montreal, Quebec, H2X 1R9, Canada

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Montreal, Quebec, H3T 1E2, Canada

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Novartis Investigative Site

Québec, Quebec, G1J 1Z4, Canada

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Novartis Investigative Site

Beijing, 100036, China

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Novartis Investigative Site

Guangzhou, 510060, China

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Novartis Investigative Site

Shanghai, 200127, China

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Novartis Investigative Site

Ostrava, Poruba, 708 52, Czechia

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Novartis Investigative Site

Olomouc, 779 00, Czechia

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Prague, 150 06, Czechia

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Novartis Investigative Site

Saint-Cloud, Hauts De Seine, 92210, France

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Angers, 49055, France

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Bordeaux, 33076, France

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Novartis Investigative Site

Bron, 69677, France

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Clermont-Ferrand, 63011, France

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Rouen, 76038, France

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Saint-Herblain, 44805, France

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Munich, Bavaria, 81377, Germany

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Cologne, North Rhine-Westphalia, 50937, Germany

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Aachen, 52074, Germany

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Augsburg, 86179, Germany

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Berlin, 10249, Germany

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Essen, 45147, Germany

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Münster, 48149, Germany

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Novartis Investigative Site

Rostock, 18057, Germany

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Novartis Investigative Site

Athens, 106 76, Greece

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Novartis Investigative Site

Athens, 11528, Greece

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Novartis Investigative Site

Thessaloniki, 540 07, Greece

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Novartis Investigative Site

Debrecen, Hajdu Bihar Megye, 4032, Hungary

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Budapest, H 1122, Hungary

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Budapest, H-1083, Hungary

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Novartis Investigative Site

Beersheba, 8457108, Israel

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Haifa, 3109601, Israel

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Jerusalem, 9112001, Israel

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Petah Tikva, 4941492, Israel

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Tel Aviv, 6423906, Israel

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Novartis Investigative Site

Brescia, BS, 25123, Italy

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Novartis Investigative Site

Cona, FE, 44124, Italy

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Genova, GE, 16132, Italy

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Rozzano, MI, 20089, Italy

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Pisa, PI, 56126, Italy

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Novartis Investigative Site

Roma, RM, 00168, Italy

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Novartis Investigative Site

Negrar, VR, 37024, Italy

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Novartis Investigative Site

Milan, 20141, Italy

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Novartis Investigative Site

Kashiwa, Chiba, 277-8577, Japan

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Novartis Investigative Site

Sapporo, Hokkaido, 060-8648, Japan

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Novartis Investigative Site

Kobe, Hyōgo, 6500047, Japan

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Novartis Investigative Site

Yokohama, Kanagawa, 236-0004, Japan

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Novartis Investigative Site

Chuo Ku, Tokyo, 1040045, Japan

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Novartis Investigative Site

Fukuoka, 811-0213, Japan

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Novartis Investigative Site

Fukuoka, 812-0033, Japan

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Novartis Investigative Site

Fukuoka, 8128582, Japan

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Novartis Investigative Site

Fukushima, 9601295, Japan

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Ishikawa, 9208641, Japan

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Novartis Investigative Site

Kyoto, 6068507, Japan

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Novartis Investigative Site

Petaling Jaya, Selangor, 46050, Malaysia

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Novartis Investigative Site

Kuala Lumpur, 59100, Malaysia

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Novartis Investigative Site

Mexico City, Mexico City, 14050, Mexico

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Novartis Investigative Site

Huxquilucan, 52763, Mexico

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Novartis Investigative Site

Amsterdam, 1066 CX, Netherlands

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VA Caribbean Healthcare System

San Juan, 00921, Puerto Rico

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Novartis Investigative Site

Singapore, 119074, Singapore

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Novartis Investigative Site

Singapore, 168583, Singapore

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Novartis Investigative Site

Bratislava, 83310, Slovakia

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Novartis Investigative Site

Košice, 041 91, Slovakia

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Novartis Investigative Site

Nitra, 949 01, Slovakia

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Novartis Investigative Site

Trenčín, 911 01, Slovakia

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Novartis Investigative Site

Granada, Andalusia, 18014, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08025, Spain

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Novartis Investigative Site

El Palmar, Murcia, 30120, Spain

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Novartis Investigative Site

Barcelona, 08036, Spain

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Novartis Investigative Site

Madrid, 28040, Spain

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Novartis Investigative Site

Madrid, 28041, Spain

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Novartis Investigative Site

Seville, 41013, Spain

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Novartis Investigative Site

Valencia, 46010, Spain

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Novartis Investigative Site

Geneva, 1211, Switzerland

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Novartis Investigative Site

Lucerne, 6006, Switzerland

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Novartis Investigative Site

Zurich, 8063, Switzerland

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Novartis Investigative Site

Taipei, 10002, Taiwan

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Novartis Investigative Site

Taipei, 103616, Taiwan

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Novartis Investigative Site

Taipei, 11217, Taiwan

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Novartis Investigative Site

Taoyuan, 33305, Taiwan

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Novartis Investigative Site

Bristol, Avon, BS2 8ED, United Kingdom

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Novartis Investigative Site

Guildford, Surrey, GU2 7XX, United Kingdom

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Novartis Investigative Site

Sutton, Surrey, SM2 5PT, United Kingdom

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Novartis Investigative Site

Coventry, CV2 2DX, United Kingdom

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Novartis Investigative Site

London, NW3 2QG, United Kingdom

RECRUITING

MeSH Terms

Interventions

Lutetium-177

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2023
• First Posted: July 11, 2023
• Study Start: March 12, 2024
• Primary Completion (Estimated): April 25, 2028
• Study Completion (Estimated): October 3, 2031
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

HU (3); PR (1); IL (5); SG (2); MY (2); SL (4); ME (2); FR (7); CA (8); IT (8); TW (4); AU (2); CN (3); NL (1); JP (11); DE (8); GR (3); BE (3); BR (1); CZ (3); ES (8); CH (3); US (38); AR (3); GB (5)