LuCarbo - a Study of 177Lu-PSMA-617 Plus Carboplatin in Metastatic Castrate-resistant Prostate Cancer

NCT06303713 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 23-693
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to see whether the combination of a chemotherapy drug, carboplatin, along with the radioligand treatment, 177Lu-PSMA-617, is safe in treating prostate cancer and whether the combination is effective in shrinking or preventing growth of prostate cancer. The names of the study drugs used in this research study are:

• Carboplatin (A type of chemotherapy)
• 177Lu-PSMA-617 (A type of radioligand therapy)

Conditions

Metastatic Castration-resistant Prostate Cancer; Prostate Cancer; Metastatic Prostate Cancer

Keywords

Prostate Cancer; Metastatic Prostate Cancer; Metastatic Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) or the Recommended Phase 2 dose (RP2D) of carboplatin administered in combination with 177Lu-PSMA-617

  The RP2D will be the highest administered dose level with ≤1 dose-limiting toxicities (DLTs) out of 6 treated patients.

  First 6 weeks of treatment

Secondary Outcomes (4)

• PSA response rate (PSA reduction by ≥50% from baseline).

  Through study completion, an average of 1 year

• Overall Response Rate (ORR)

  Through study completion, an average of 1 year

• Radiographic Progression-Free Survival (rPFS)

  Through study completion, an average of 1 year

• Overall Survival (OS)

  Through study completion, an average of 1 year

Study Arms (2)

Phase 1A: Dose Escalation

EXPERIMENTAL

Participants will be enrolled in a 3+3 dose escalation design to establish a maximum tolerated dose (MTD) of carboplatin, starting at Dose Level 1 and escalating to Dose Level 2 or 3. * Baseline visit. * Day 1 of Cycles 3 and 5: Tumor assessment radiologic scans. * Cycle 1 through End of Treatment: * Days 1 and 22 of 42-day cycle: Predetermined dose of carboplatin every 3 weeks for a maximum of up to 6 cycles. * Day 2 of 42-day cycle: Predetermined dose of 177Lu-PSMA-617 every 6 weeks for a maximum of up to 6 cycles. * End of treatment visit. * Follow up visits in-office or via telephone. If 0 out of 3 participants experience a dose-limiting toxicity (DLT), the study will proceed to the next dose level. If 1 or more participants experience a DLT, this dose level is declared the MTD and study will not proceed to expansion. If 1 out of 6 participants at the highest dose level experience DLTs, this is the recommended Phase 1B dose.

Drug: Carboplatin; Drug: 177Lu-PSMA-617

Phase 1B: Dose Expansion

EXPERIMENTAL

19 additional participants will be enrolled at the RP2D of carboplatin and will complete: * Baseline visit. * Day 1 of Cycles 3 and 5: Tumor assessment radiologic scans. * Tumor biopsy at baseline and at 12 weeks. * Cycle 1 through End of Treatment: * Days 1 and 22 of 42 day cycle: Predetermined dose of carboplatin every 3 weeks for a maximum of up to 6 cycles. * Day 2 of 42 day cycle: Predetermined dose of 177Lu-PSMA-617 every 6 weeks for a maximum of up to 6 cycles. * End of treatment visit. * Follow up visits in-office or via telephone.

Drug: Carboplatin; Drug: 177Lu-PSMA-617

Interventions

Carboplatin DRUG

Platinum coordination compound, premixed aqueous solution of 10mg/ML, via intravenous (into the vein) infusion per protocol.

Also known as: C6H12N2O4Pt, Platinum, diammine [1,1-cyclobutanedicarboxylato(2-)- O,O']-, (SP-4-2)

Phase 1A: Dose Escalation; Phase 1B: Dose Expansion

177Lu-PSMA-617 DRUG

Radioligand therapy, single-dose vial, via intravenous (into the vein) infusion per protocol.

Also known as: Pluvicto, Lutetium Lu 177 vipivotide tetraxetan, C49H71N9O16

Phase 1A: Dose Escalation; Phase 1B: Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically or cytologically confirmed prostate adenocarcinoma without histologic variants comprising \>50% of the sample as determined by pathology review at an academic medical center; men without histologic or cytologic confirmation are eligible provided there is unequivocal evidence of prostate cancer (eg. very high PSA) in the view of the treating physician.
• Age ≥ 18years. Children under age 18 are excluded as prostate cancer is a disease of adults.
• Progressive disease at study entry, as defined by either one of the following:
• Sequence of at least 2 rising PSA values at a minimum of 1-week intervals with the last result being ≥1.0 ng/mL if confirmed PSA rise is the only indication of progression. Patients who received an anti-androgen (flutamide, bicalutamide or nilutamide) must have PSA progression ≥4 weeks after the last dose.
• Radiographic progression per RECIST 1.1 for soft tissue and/or per PCWG3 for bone (i.e. appearance of ≥2 new bone lesions), with or without PSA progression.
• Presence of ≥1 metastatic lesion metastatic lesion present on baseline CT, MRI, or bone scan imaging obtained ≤28 days prior to beginning study therapy.
• Prior receipt of at least one taxane chemotherapy (docetaxel or cabazitaxel) and at least one ARPI (abiraterone, enzalutamide, apalutamide or darolutamide) in the localized, recurrent or metastatic setting. Prior treatment with a PARP inhibitor(s) is permitted. Prior treatment with Ra-223 is permitted, providing that the last dose of Ra-223 was ≥90 days prior to study entry.
• Presence of ≥1 PSMA-avid lesion (with uptake \> liver) on baseline/screening 68GaPSMA-11 PSMA-PET.
• Serum testosterone level must be ≤50ng/dL (1.73 nmol/L) at the screening visit. Participants who have not undergone bilateral orchiectomy are required to continue LHRH/GnRH agonists/antagonists) throughout the study. Use of relugolix is permitted.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
• Adequate organ and marrow function as per the below table:
• System Laboratory Value
• Hematologic
• ANC ≥1.5×109/L
• Platelets ≥100×109/L

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 4 weeks prior to planned cycle 1 day 1 of study treatment.
• Participants who have received anti-neoplastic intervention or experimental antineoplastic therapy within 14 days of planned cycle 1 day 1 of study therapy.
• Participants who are receiving any other investigational agents.
• Participants who have previously received 177Lu-PSMA-617.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 177Lu-PSMA-617 and carboplatin.
• Participants with untreated brain metastases. Participants with treated brain metastases are eligible if follow-up brain imaging at least 4 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression and ongoing corticosteroids are not required. Participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy.
• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
• Concurrent active malignancy whose natural history or treatment has the potential to interfere with safety or efficacy assessment of the investigational regimen. Patients with non-melanomatous skin cancer, superficial bladder cancer, cancer not needing active therapy for at least 2 years, cancer for which the treating investigator deems the subject to be in remission, or any prior malignancy that was treated with curative intent (no evidence of disease for at least 3 years) are permitted to enroll.
• The participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Novartis: collaborator

Study Sites (3)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Carboplatin; Platinum; Pluvicto

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Study Officials

• Praful Ravi, MB BCHir, MRCP

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: February 27, 2024
• First Posted: March 12, 2024
• Study Start: May 22, 2024
• Primary Completion (Estimated): October 19, 2026
• Study Completion (Estimated): March 19, 2027
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu.

Locations

US (3)