Trial Title:
LuCarbo - a Study of 177Lu-PSMA-617 Plus Carboplatin in Metastatic Castrate-resistant Prostate Cancer
NCT ID:
NCT06303713
Condition:
Prostate Cancer
Metastatic Prostate Cancer
Metastatic Castration-resistant Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Carboplatin
Pluvicto
Conditions: Keywords:
Prostate Cancer
Metastatic Prostate Cancer
Metastatic Castration-resistant Prostate Cancer
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Platinum coordination compound, premixed aqueous solution of 10mg/ML, via intravenous
(into the vein) infusion per protocol.
Arm group label:
Phase 1A: Dose Escalation
Arm group label:
Phase 1B: Dose Expansion
Other name:
C6H12N2O4Pt
Other name:
Platinum, diammine [1,1-cyclobutanedicarboxylato(2-)- O,O']-, (SP-4-2)
Intervention type:
Drug
Intervention name:
177Lu-PSMA-617
Description:
Radioligand therapy, single-dose vial, via intravenous (into the vein) infusion per
protocol.
Arm group label:
Phase 1A: Dose Escalation
Arm group label:
Phase 1B: Dose Expansion
Other name:
Pluvicto
Other name:
Lutetium Lu 177 vipivotide tetraxetan
Other name:
C49H71N9O16
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)
Detailed description:
This is a phase 1 dose-escalation and dose-expansion trial of carboplatin in combination
with 177Lu-PSMA-617 in participants with metastatic castrate-resistant prostate cancer
(mCRPC). The study will take place in two parts: Phase 1a to define the recommended phase
2 dose (RP2D) and Phase 1b to further assess safety and preliminary clinical activity of
the combination regimen.
The U.S. Food and Drug Administration (FDA) has not approved carboplatin for prostate
cancer but it has been approved for other uses.
The U.S. FDA has approved 177Lu-PSMA-617 as a treatment option for prostate cancer.
The research study procedures include screening for eligibility and study treatment
visits, tumor biopsies, x-rays, Computerized Tomography (CT) scans, Magnetic Resonance
Imaging (MRI) scans, Positron Emission Tomography (PET) scans, and blood tests.
It is expected that about 35 people will take part in this research study.
Novartis is supporting this research study by providing 177Lu-PSMA-617, as well as
research funding.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
- Hemoglobin ≥9g/dL (≥90g/L), independent of transfusions
- Hepatic
- Total bilirubin ≤1.5 × ULN OR <2 × ULN if known or suspected Gilbert's syndrome
- ALT and AST ≤3 × ULN OR ≤5 × ULN if liver metastases present
- Renal
--eGFR ≥30 mL/min/1.73 m2 (based on Cockcroft-Gault formula OR 24 hour urine
collection
- Presence of a recurrent/metastatic lesion (bone or soft tissue) amenable to
image-guided percutaneous biopsy adequate for next generation sequencing (NGS), and
planned to undergo core biopsy after trial registration but prior to cycle 1 day 1
of therapy.
Confirmation of adequacy of this biopsy material for NGS is NOT required for initiation
of therapy.
- Willingness to undergo core biopsy of a recurrent/metastatic lesion adequate for NGS
after approximately 12 weeks of study treatment.
- Participants with a prior or concurrent malignancy whose natural history or
treatment does not have the potential to interfere with the safety or efficacy
assessment of the investigational regimen are eligible for this trial.
- The effects of 177Lu-PSMA-617 and carboplatin on the developing human fetus are
unknown. For this reason and because chemotherapies and radioligand therapies are
known to be teratogenic, men must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry and for the
duration of study participation. Men treated or enrolled on this protocol must also
agree to use adequate contraception for the duration of study participation, and at
least 14 weeks following the last dose of 177Lu-PSMA-617.Should a woman become
pregnant or suspect she is pregnant while her partner is participating in this
study, she should inform her treating physician immediately. Female partners of
child-bearing potential should also use highly effective birth control methods
throughout the male participant's study treatment and for at least 14 weeks
following the last dose of 177Lu-PSMA-617.
- Ability to understand and the willingness to sign a written informed consent
document. (Providing consents in as many languages as possible is encouraged)
Exclusion Criteria
- 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).
Gender:
Male
Gender based:
Yes
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Beth Israel Deaconess Medical Center
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Daniel Fein, MD
Phone:
617-667-2100
Email:
dfein@bidmc.harvard.edu
Investigator:
Last name:
Daniel Fein, MD
Email:
Principal Investigator
Facility:
Name:
Brigham and Women's Hospital
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Praful Ravi, MB BCHir, MRCP
Phone:
617-632-3466
Email:
Praful_Ravi@DFCI.HARVARD.EDU
Investigator:
Last name:
Praful Ravi, MB BCHir, MRCP
Email:
Principal Investigator
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Praful Ravi, MB BChir, MRCP
Phone:
617-632-3466
Email:
praful_ravi@dfci.harvard.edu
Investigator:
Last name:
Praful Ravi, MB BCHir, MRCP
Email:
Principal Investigator
Start date:
May 22, 2024
Completion date:
July 19, 2026
Lead sponsor:
Agency:
Dana-Farber Cancer Institute
Agency class:
Other
Collaborator:
Agency:
Novartis
Agency class:
Industry
Source:
Dana-Farber Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06303713