New trial (S1802) for treatment of men with newly diagnosed, metastatic prostate cancer


Earlier this month we had mentioned hearing about a new trial to explore whether local ablation of the primary tumor could improve the outcomes of men initially diagnosed with metastatic prostate cancer.

We have now heard officially that the Southwest Oncology Group (SWOG) trial no. S1802 has just started to enroll patients to this trial, formally known as the “Phase III randomized trial of standard systemic therapy (SST) versus standard systemic therapy plus definitive treatment (surgery or radiation) of the primary tumor in metastatic prostate cancer”.

The core goals of this study are to :

  • Determine whether patients live longer, or longer free of cancer, if their primary prostate tumor is removed by surgery, or treated with radiation, after they receive standard systemic therapy
  • Determine if patients experience any difference in side effects, including pain or kidney function
  • Collect tissue and blood samples for the study of the effects of tumor removal on the biology of surrounding tissue and determine whether there are impacts on cancer growth or spread

What this means is that newly diagnosed men with metastatic prostate cancer who agree to participate in this trial will be randomized to treatment with either:

  • Standard systemic therapy alone or
  • Standard systemic therapy + definitive ablative treatment  of the primary tumor (with either surgery or radiation therapy of some type)

Since we have yet to see any data about this trial on the ClinicalTrials.gov web site, there are a lot of things we still do not yet know, including:

  • The number of patients to be enrolled into the trial
  • How long it will take for the trial to enroll enough patients and be carried out
  • The precise study endpoints
  • The precise forms of radiation therapy that might be acceptable for ablation of the primary tumor
  • The forms of “standard” systemic therapy that SWOG now considers to be acceptable for the treatment of newly diagnosed metastatic prostate cancer
  • Exactly which sites are going to be enrolling patients (here in America as well as elsewhere)

Your sitemaster’s current assumption (as previously indicated) is that the current “standard” forms of systemic therapy will include:

  • Standard androgen deprivation therapy (ADT) + docetaxel chemotherapy (as previously defined by the CHAARTED and the STAMPEDE trials)
  • Standard ADT + abiraterone acetate + prednisone (as previously defined by the LATITUDE and the STAMPEDE trials)

For more information about this trial, at the current time, newly diagnosed patients should call 1-800-CANCER and then ask for information about SWOG trial S1802. As soon as we can, we will see if we can get hold of the NCT number so that we can all look up the details on ClinicalTrials.gov. However, swe do know that to be eligible to participate in the trial a patient must

  • Have a proven diagnosis of adenocarcinoma of the prostate.
  • Have an intact prostate
  • Have evidence of metastatic disease based on appropriate imaging results
  • Have received no more than 28 weeks of standard treatment
  • Be over the age of 18
  • Have a complete physical exam and medical history taken
  • Have documentation of PSA levels, testosterone levels, and other tests

We do know that this trial will be enrolling patients at a significant number of different sites.

Last but not least, this is an important trial because it may help us to come much closer to knowing what is the “best” form of treatment for men newly diagnosed with hormone-naive, metastatic prostate cancer.

13 Responses

  1. The target accrual is 1,273 patients. The trial will take up to 5 years to accrue this many patients, but it could be accomplished sooner. The patients will be monitored for 8 years.

    The primary objective of the study is:

    — To compare overall survival in metastatic prostate cancer patients who are randomized to standard systemic therapy (SST) plus definitive treatment of the primary tumor versus standard systemic therapy alone.

    The secondary objectives are:

    (a) To compare overall survival in metastatic prostate cancer patients who received SST plus surgical excision of the primary tumor versus SST alone in the subset who specify the surgical intent stratification factor.
    (b) To compare the rate of symptomatic local progression between the treatment arms.
    (c) To compare progression-free survival (PFS) between the two treatment arms.
    (d) To compare rates of progression-free survival between arms for the subsets of patients with and without metastasis-directed therapy (MDT) to oligometastatic sites

    The forms of approved radiation are EBRT based, i.e., no brachytherapy or proton therapy. So SBRT, IMRT, and 3D-CRT are approved.

    By definition in the ICF: Standard Systemic Therapy (SST): Standard of care systemic therapy per the NCCN guidelines includes androgen deprivation therapy (ADT) with or without the use of docetaxel chemotherapy (up to 6 cycles). This is based on the CHAARTED study, which demonstrated a survival advantage with the early use of docetaxel in men with hormone-naive M1 prostate cancer. Using SST as defined by NCCN guidelines will allow for flexibility in standards over the time frame of the study. For example, with LATITUDE and STAMPEDE results use of abiraterone in front-line therapy has recently become a standard option.

    All SWOG participants, approximately 47 institutions, have been IRB approved. The trial is also being considered in six additional nations and through ECOG sites. It’s worth noting that the primary sponsor of this trial to date has been M. D. Anderson Cancer Center (where the principal investigator is based).

    I expect the NCT number at ClinicalTrials.gov to be released in the coming days.

  2. Here’s the trial info:
    https://clinicaltrials.gov/ct2/show/NCT03678025

    As I understand it, patients may have had docetaxel + ADT as part of earlier treatment in up to the 28 weeks prior to randomization, but they cannot have it after randomization. They may have abiraterone as part of their systemic therapy before or after randomization. I wonder why abiraterone is allowed but not docetaxel.

    It is also unclear whether they will allow ePLND with prostatectomy, or whole pelvic radiation. It is also unclear whether they allow SBRT or boost with brachytherapy or protons. They do allow metastasis-directed therapy pre-randomization but not afterwards.

  3. Thanks for this additional information Tony.

  4. Tony:

    The clinicaltrials.gov listing says that docetaxel may have been part of pre-randomization treatment but is not part of post-randomization standard of care. It says:

    Active Comparator — Arm I:
    Participants receive 1 acceptable form of SST as in Induction except for treatment with docetaxel and prednisone.

    Experimental: Arm II (SST, prostatectomy or radiation therapy):
    Participants receive 1 acceptable form of SST as in Induction except for treatment with docetaxel and prednisone.

    This seems to be at odds with what you wrote. Is it an error?

    Could you please also address the other points I raised with regard to pelvic lymph node treatment? I understand from what you wrote that brachytherapy and proton boost therapy are not allowed, and since M. D. Anderson does not offer SBRT for prostate cancer, that is effectively off the table too.

  5. Allen, thank you. You are faster than my protocol coordinator though I am not surprised. :-)

  6. Allen,

    I will get refreshed on that. SST as outlined by NCCN does in fact consider docetaxel + prednisone. I know the 24 to 28 week time frame was decided with Doce + 6 (every 3 weeks) in mind. Stay tuned.

  7. I think it’s just confusion. I have the protocol in hand and here’s the skinny:

    The Clinical Trials.gov site is correct and my post is correct. Here’s why:

    Step 1 Registration.
    The patient registration must happen before receiving SST and not more than 28 days after detection. Once registered, the patient will start SST for up to 28 weeks optionally including docetaxel+6 with or without prednisone per CHAARTED and at the treating physicians discretion.

    Step 2 Randomization.
    If the patient shows no disease progression they will be randomized to SST alone in arm 1 or SST+definitive treatment. Once the patient has been randomized they cannot receive docetaxel and remain on protocol. The Clinicaltrials.gov website addresses after randomization and shows the arms as “Excluding Docetaxel” and after randomization that is correct.

    The only likely reason to add docetaxel after randomization would be disease progression. This round of docetaxel would not be in compliance with CHAARTED and thus not allowed in our trial.

  8. So then SST post-randomization may not include docetaxel. They may or may not have had docetaxel pre-randomization. I assume they may or may not have had Zytiga pre-randomization as well, However, you exclude docetaxel post-randomization but not Zytiga (per STAMPEDE/LATITUDE)? Why the difference?

  9. Allen,

    The logical reasoning for no docetaxel after randomization is again the lack of evidence that a man who is still responsive to hormonal suppression that far out after Dx is outside the design for CHAARTED. Additionally, docetaxel chemotherapy in the standard of care is six doses at 3-week dose intervals while treatment with abiraterone is not limited to that timeframe. It is reasonable, based on both LATITUDE and STAMPEDE, to continue use of abiraterone beyond that interval and so it is acceptable to continue its use after randomization in S1802.

    Now for patients that did not add abiraterone to their initial treatment but still achieved a significant response with an LHRH, adding abiraterone later is problematic as we don’t have that data either. Of course adding docetaxel AND abiraterone is also problematic but there are new trials in the works for that comparison. For this trial, its either/or. If abiraterone is chosen then clearly continuing beyond randomization is expected. I suspect, however, that not adding abiraterone initially and adding it later without progression is not acceptable. Again from the actual protocol:

    “Using SST as defined by NCCN guidelines will allow for flexibility in standards over the time frame of the study. For example, with LATITUDE and STAMPEDE results use of abiraterone in FRONT-LINE therapy has recently become a standard option.”

    “Front-Line” is the key wording. This is silent on adding abiraterone without progression later.

    I’ll be in front of the PI today. Stay tuned.

  10. I spoke to Dr. Brian Chapin. He said that this is the most common question on the trial, “After randomization, why is docetaxel excluded, and abiraterone not excluded for inclusion later”.

    I am on target in my last post. Abiraterone can be continued as long as it was in the front line at the beginning. And it is LATITUDE and STAMPEDE that recommend up to 2 years on for the benefits noted n those trials. And it is not standard of care to add abiraterone “mid stream” to a patient that has responded well to ADT2 with any form of testosterone suppression plus bicalutamide.

    Brian noted that this was decided, and I recall the discussion was decided at the end, that it was important to keep the therapies consistent in the arms. He did also state that while many oncologists are adding abiraterone with docetaxel in the front line, there are still no trials completed that have changed the standard of care (SoC) to doing this. Those trials are ongoing, and if they do produce a change in SoC then that it will be allowed and monitored as a separate subset within S1802.

    So after randomization to this date there can be no introductions of either docetaxel or abiraterone. But abiraterone can be continued on protocol per NCCN guidelines on the front end.

  11. Tony:

    But LATITUDE also only looked at newly diagnosed patients. STAMPEDE only included men who had not been pre-treated with hormone therapy, and 97% of men in the control group and 93% in the abiraterone group were also newly diagnosed (there was no statistically significant benefit in the recurrent men). If it is “outside the range of CHAARTED,” it is also outside the range of LATITUDE and STAMPEDE. Perhaps the PI can clear up this discrepancy.

  12. I think we’re saying the same thing. Starting docetaxel after 28 weeks or starting abiraterone after 28 weeks is outside the three trials. But continuing abiraterone after 28 weeks is within protocol thus it is not excluded for the purpose of realizing the benefits found in the abiraterone trials. Doce + 6 is expected to be complete by week 28 and thus why that time table was set.

  13. Gotcha — thanks!

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