Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer

Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexMale
Age18+
SponsorVA Office of Research and Development

About this trial

This is a prospective, open-label, multi-center seamless phase II to phase III randomized clinical trial designed to compare SST with or without PET-directed local therapy in improving the castration-resistant prostate cancer-free survival (CRPC-free survival) for Veterans with oligometastatic prostate cancer. Oligometastasis will be defined as 1-10 sites of metastatic disease based on the clinical determination of the LSI which incorporates all imaging, clinical, and pathologic data available.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

None

Disqualifiers

Any current or prior evidence of castration-resistant prostate cancer, defined as two consecutive rises in serum PSA, obtained at a minimum of 1-week interval, with the final PSA value >/= 1 ng/ml, while having a total testosterone < 50 ng/dl).

Adequately treated non-melanomatous skin cancer;

Adequately treated Stage 0, I, or II cancer from which the patient is currently in complete remission; or

Any other cancer from which the patient has been disease free for three years.

Trial design

Design model

Parallel

Treatments tested in this trial

  • PET-directed Local Therapy using Surgery

    Procedure/Surgery

    Surgery will be used to treat metastases.

  • PET-directed Local Therapy using Radiation

    Radiation

    Radiation therapy will be used to treat metastases. Radiation options include: 1. Stereotactic body radiotherapy (SBRT) using 1-10 fractions 2. Conventionally fractionated radiotherapy using elective nodal radiotherapy and a simultaneous integrated boost to involved nodes The selection of the form of metastasis-directed radiotherapy for each metastasis will be determined using shared decision-making between the treating physician and the Veteran.

  • Salvage Local Therapy for locally recurrent disease

    Other intervention

    For Veterans who have a local recurrence in addition to oligorecurrent metastatic lesions, they will undergo salvage local therapy using brachytherapy, SBRT, surgery, cryotherapy or HIFU. The selection of modality of salvage local therapy will be determined using shared decision-making between the treating physician and Veteran.

  • Goserelin, Histrelin, Leuprolide & Triptorelin

    Drug

    Androgen deprivation therapy (ADT) using an LHRH agonist

  • ADT + Nilutamide, Flutamide, & Bicalutamide

    Drug

    ADT adding anti-androgen therapy to an LHRH agonist

  • Degarelix & Relugolix

    Drug

    ADT using an LHRH Antagonist.

  • ADT + Docetaxel +/- prednisone

    Drug

    Enhanced SST using chemohormonal therapy

  • ADT + Abiraterone + Prednisone

    Drug

    Enhanced SST using Abiraterone + Prednisone

  • ADT + Abiraterone + Methylprednisolone

    Drug

    Enhanced SST using Abiraterone + Methylprednisolone

  • ADT + Apalutamide

    Drug

    Enhanced SST using ADT + Apalutamide

  • ADT + Enzalutamide

    Drug

    Enhanced SST using ADT + Enzalutamide

  • Prostate-directed Radiation for De novo oligometastatic prostate cancer

    Radiation

    Veterans in ARM 1 will receive prostate-directed RT only and NO treatment to any nodal or distant metastatic sites. Acceptable dose/fractionations include 55 Gy in 20 fractions and 36 Gy in 6 fractions. Veterans in ARM 2 should receive prostate-directed local therapy using radiotherapy or radical prostatectomy in addition to PET-directed local therapy to metastases.

Treatment groups

464 Participants
are divided into 2 treatment groups
Group A: Standard Systemic Therapy (SST)Active comparator 9 interventions
Group B: SST + PET-directed local therapyExperimental treatment 12 interventions

Trial outcomes

Primary outcomes

1

Castration-resistant prostate cancer-free survival (CRPC-free survival)

CRPC-free survival is a time-to-event outcome defined as the length of time from randomization to the first occurrence of failure. The following are forms of failure in the setting of a castrate testosterone level: PSA progression, radiographic progression, symptomatic skeletal event due to progression, and death.

Time frame
4 years

Secondary outcomes

1

Radiographic progression-free survival (rPFS)

rPFS is a time-to-event outcome defined as the length of time from randomization to radiographic progression of prostate cancer or death.

Time frame
4 years
2

Clinical progression-free survival (cPFS)

cPFS is a time-to-event outcome defined as the length of time from randomization to radiographic progression on conventional imaging, symptomatic skeletal event due to progression, or death.

Time frame
4 years
3

Freedom from index lesion progression (FFILP)

FFILP is a time-to-event outcome defined as the length of time from randomization to progression of any of the enrollment index oligorecurrent lesions.

Time frame
4 years
4

New metastasis-free survival (MFS)

New MFS is a time-to-event outcome (MFS) defined as the length of time from randomization to the development of a new metastasis that was not present at the time of enrollment, or death.

Time frame
4 years

Other outcomes

Sponsors and contacts

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