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Early Rising PSA Endocrine Treatment Versus Chemo-endocrine Therapy- SPCG14

Primary Purpose

Prostatic Neoplasms

Status

Unknown status

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Antiandrogen

Antiandrogen+docetaxel

About this trial

This is an interventional treatment trial for Prostatic Neoplasms focused on measuring Non-metastatic Prostate Cancer

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

Men > 18 and ≤80 years of age.
WHO/ECOG performance status 0 - 1 (WHO: World Health Organization; ECOG: Eastern Cooperative Oncology Group )
Histological proven adenocarcinoma of the prostate.
Patients who are planned to receive antiandrogen (bicalutamide 150 mg x 1) treatment,
After curative treatment
- Prostatectomy: PSA > 10 OR PSA DT < 12 months and PSA > 0.5 (PSA doubling time calculation must start at a minimum value of > 0.5)
- Radiation: PSA > +2.0 above nadir and PSA >10 OR PSA DT < 12 months and PSA > 0.5. (PSA bouncing after radiotherapy should be excluded according to the local traditions, and PSA doubling time calculation must start at a minimum value of > 0.5)
In locally advanced (or local not suitable for curative therapy) prostate cancer patients, PSA < 100 is required before inclusion AND one of the following
- PSA DT < 12 months or
- PSA >20 or
- Gleason score 8-10
Previous hormonal therapy in conjunction with radiotherapy is allowed, provided that the total duration of therapy does not exceed 12 months and has to be stopped > 12 months ago.
Testosterone value > 5 nmol/l
Adequate haematological-, liver- and kidney function. WBC(white blood cell ) 3.5 x 109/L ANC(absolute neutrophil count ) 1.5 x 109/L Platelet Count 150 x 109/L Haemoglobin > 120 g/L Total bilirubin ≤ ULN (upper limit of normal) unless due to Gilbert's disease Creatinine ≤ 1.5 x ULN or creatinine clearance of 60 cc/min or corresponding Iohexol clearance value ASAT(aspartate aminotransferase )/ALAT(alanine aminotransferase) ≤ 1.5 x ULN ALP (Alkaline phosphatase) < 1.5 x ULN
Negative bone scan performed no more than 3 months prior to randomisation.
Additional CT or ultrasound of thorax, abdomen and/or pelvis is optional.
Written informed consent.

Exclusion Criteria:

Positive bone scan
Any distant metastasis detected by CT or ultrasound
Patients with a history of previous malignant disease. Exceptions should be made for basal cell carcinoma (BCC) and squamous cell carcinoma of the skin. Exceptions should also be made for curatively treated malignant disease, which has been disease free for the past 5 years.
Previous chemotherapy or randomised in SPCG 12/AdPro or SPCG 13/AdRad (SPCG: Scandinavian Prostate Cancer Group).
Systemic corticosteroids within 6 months prior to randomisation.
Unstable cardiovascular disease, including myocardial infarction, within 6 months prior to randomisation.
Active untreated infectious disease, including tuberculosis, MRSA (Methicillin-resistant Staphylococcus aureus.
Active gastric ulcer.
Known hypersensitivity to Polysorbate 80 (an excipient of docetaxel)
Other serious illness or medical condition
Symptomatic peripheral neuropathy ≥ CTCAE grade 2.
Patients who by altered physical or psychological state not are able to co-operate or participate in the trial.

Sites / Locations

Copenhagen University hospital, Rigshospitalet
Kuopio University Hospital
Turku University Hospital
Erasmus Medical Center Rotterdam
Sahlgrenska University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Antiandrogen

Antiandrogen + docetaxel

Arm Description

Antiandrogen (bicalutamide 150 mg x 1) p.o. alone,

Antiandrogen (bicalutamide 150 mg x 1) p.o. + Docetaxel 75 mg/m2 (maximum 2.0 m2 ) i.v. q 3 weeks x up to 8-10 cycles.

Outcomes

Primary Outcome Measures

Progression free survival

Progression free survival defined as the time from randomization to the date of first documentation of: PSA progression PSA progression is considered to occur when PSA is +2.0 ng/ml above nadir. A confirmatory PSA must be taken no less than 6 weeks following the first rising PSA above nadir +2.0 ng/ml. If that confirmatory PSA also exceeds the above parameters, then progression has occurred. If the confirmatory PSA fails to confirm progression, then the patient will remain on study. Radiographic progression Outcome in patients who develop radiographically metastatic disease while on study will be defined as progression independent of their respective PSA values. These patients will be followed for evaluation of survival. - Death Death due to prostate cancer in the absence of previous documentation of disease progression,

Secondary Outcome Measures

Difference between groups in PSA doubling time (PSADT).

The PSADT can be calculated by the natural log of 2 (0.693) divided by the slope of the relation between the log of PSA and the time of PSA measurement.

Difference between groups regarding QoL

The quality of life (QoL) will be assessed using the FACT-P-T disease-specific subscale. The scoring will be in accordance with version 4 of the FACT manual.

Difference between groups regarding metastasis free survival

Metastasis free survival will be assessed yearly by bone-scan after first PSA progression until the date of first documented metastasis on bone scan, date of death from any cause, whichever came first, assessed up to 100 months

Difference between groups regarding overall survival

Survival will be assessed yearly up to 100 months after inclusion

Difference between groups regarding cancer specific survival

Cancer specific survival will be assessed yearly up to 100 months after inclusion

Measurement of grade of toxicity of given treatments

Adverse events recording using NCI-CTCAE (v3.0)

Full Information

NCT ID

NCT03119857

First Posted

May 14, 2016

Last Updated

August 12, 2021

Sponsor

Göteborg University

Collaborators

Sahlgrenska University Hospital, Västra götalands regionen (Huvudman)

1. Study Identification

Unique Protocol Identification Number

NCT03119857

Brief Title

Early Rising PSA Endocrine Treatment Versus Chemo-endocrine Therapy- SPCG14

Official Title

A Randomized, Open Label, Multicenter, Phase III, 2-Arm Study of Androgen Deprivation +/- Taxotere (Docetaxel) for Non-metastatic Prostate Cancer Patients With a Rising PSA

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Unknown status

Study Start Date

February 2009 (Actual)

Primary Completion Date

April 2023 (Anticipated)

Study Completion Date

April 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Göteborg University

Collaborators

Sahlgrenska University Hospital, Västra götalands regionen (Huvudman)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Summary In patients with prostate cancer (PC) who have only biochemically relapsed disease after curative treatment (or some locally advanced PC patients), hormonal therapy remains a de facto standard of care treatment. Adding docetaxel-based chemotherapy to a standard-of-care hormonal therapy has an increased potential to treat prostate cancer cell clones resistant to androgen withdrawal and to possibly shorten the duration of therapy needed to control the disease. This clinical trial is designed on the basis of an unmet clinical need, as well as other factors including: 1) a consensus among investigators on endpoints for studies of patients with a rising PSA, 2) the ability to identify subjects at high risk for developing radiographic metastases, 3) the fact that hormonal therapy has already been shown to improve survival when applied early in the natural history, and 4) the availability of chemotherapy such as docetaxel that can improve survival in subjects with advanced disease. It is our hypothesis that a more appropriate group of patients who may benefit from the curative potential of systemic chemo-hormonal modality is that with minimal, but detectable disease who have a high probability of developing metastatic disease, clinical symptoms and eventually death from prostate cancer in a defined time frame. The investigators hypothesize further that the approach is likely to be more effective at a time of minimal tumour burden, resulting in minimization of the overall burden of therapy and better quality of life while on treatment. This trial will determine whether any benefit is gained by adding chemotherapy to hormonal therapy alone in the population of subjects with a rising PSA. Two therapeutic approaches will be compared in this two-arm randomized clinical trial. The control Arm A provides antiandrogen (bicalutamide 150 mg x 1) alone. The experimental Arm B involves treatment with docetaxel for 8-10 cycles and antiandrogen (bicalutamide 150 mg x 1) treatment. For the schematic representation of study design please see Section 7.3.1. Subjects with a rising PSA following definitive local curative therapy will be eligible, if their PSA doubling time is < 12 months. Also PC patients planned for anti-.androgen therapy are eligible, with the same criteria. Subjects with radiographic metastases will be excluded. The primary endpoint of the trial is progression-free survival of subjects that do not experience biochemical failure at 60 months from the start of therapy. Based on the yearly number of prostate cancer patients who undergo definitive local therapies and the estimated probabilities of relapse, upwards of 400 men (if +15% improvement) in the Scandinavian countries are potential candidates for this approach.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostatic Neoplasms

Keywords

Non-metastatic Prostate Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

349 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Antiandrogen

Arm Type

Active Comparator

Arm Description

Antiandrogen (bicalutamide 150 mg x 1) p.o. alone,

Arm Title

Antiandrogen + docetaxel

Arm Type

Experimental

Arm Description

Antiandrogen (bicalutamide 150 mg x 1) p.o. + Docetaxel 75 mg/m2 (maximum 2.0 m2 ) i.v. q 3 weeks x up to 8-10 cycles.

Intervention Type

Drug

Intervention Name(s)

Antiandrogen

Intervention Type

Drug

Intervention Name(s)

Antiandrogen+docetaxel

Other Intervention Name(s)

Taxotere

Intervention Description

Antiandrogen (bicalutamide 150 mg x 1) + docetaxel (Taxotere®) 75mg/m2 (max 2.0m2) i.v. in 60 minutes on day 1. One cycle is 21 days. Docetaxel will be given for up to 8-10 cycles or until unacceptable toxicity or consent withdrawal whichever comes first. Antiemetic therapy may be used if necessary.

Primary Outcome Measure Information:

Title

Progression free survival

Description

Time Frame

From date of randomization until the date of first documented progression or date of death from any cause, which ever came first, assessed up to 60 months

Secondary Outcome Measure Information:

Title

Difference between groups in PSA doubling time (PSADT).

Description

The PSADT can be calculated by the natural log of 2 (0.693) divided by the slope of the relation between the log of PSA and the time of PSA measurement.

Time Frame

From date of randomization until the date of first documented PSADT, assessed up to 60 months

Title

Difference between groups regarding QoL

Description

The quality of life (QoL) will be assessed using the FACT-P-T disease-specific subscale. The scoring will be in accordance with version 4 of the FACT manual.

Time Frame

At date of randomization and yearly, assessed up to 60 months

Title

Difference between groups regarding metastasis free survival

Description

Time Frame

From date of randomization until the date of first documented date of metastases, assessed yearly by bone-scan after first PSA_progression until first sign of metastasis, whichever came first, assessed up to 100 months

Title

Difference between groups regarding overall survival

Description

Survival will be assessed yearly up to 100 months after inclusion

Time Frame

From date of randomization until the date of death from any cause reported yearly by the study sites up to 100 months

Title

Difference between groups regarding cancer specific survival

Description

Cancer specific survival will be assessed yearly up to 100 months after inclusion

Time Frame

From date of randomization until date of death from prostate cancer,reported yearly by the study sites up to 100 months

Title

Measurement of grade of toxicity of given treatments

Description

Adverse events recording using NCI-CTCAE (v3.0)

Time Frame

At date of randomization, during treatment and follow up questionaries until 60 months

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Men > 18 and ≤80 years of age. WHO/ECOG performance status 0 - 1 (WHO: World Health Organization; ECOG: Eastern Cooperative Oncology Group ) Histological proven adenocarcinoma of the prostate. Patients who are planned to receive antiandrogen (bicalutamide 150 mg x 1) treatment, After curative treatment Prostatectomy: PSA > 10 OR PSA DT < 12 months and PSA > 0.5 (PSA doubling time calculation must start at a minimum value of > 0.5) Radiation: PSA > +2.0 above nadir and PSA >10 OR PSA DT < 12 months and PSA > 0.5. (PSA bouncing after radiotherapy should be excluded according to the local traditions, and PSA doubling time calculation must start at a minimum value of > 0.5) In locally advanced (or local not suitable for curative therapy) prostate cancer patients, PSA < 100 is required before inclusion AND one of the following PSA DT < 12 months or PSA >20 or Gleason score 8-10 Previous hormonal therapy in conjunction with radiotherapy is allowed, provided that the total duration of therapy does not exceed 12 months and has to be stopped > 12 months ago. Testosterone value > 5 nmol/l Adequate haematological-, liver- and kidney function. WBC(white blood cell ) 3.5 x 109/L ANC(absolute neutrophil count ) 1.5 x 109/L Platelet Count 150 x 109/L Haemoglobin > 120 g/L Total bilirubin ≤ ULN (upper limit of normal) unless due to Gilbert's disease Creatinine ≤ 1.5 x ULN or creatinine clearance of 60 cc/min or corresponding Iohexol clearance value ASAT(aspartate aminotransferase )/ALAT(alanine aminotransferase) ≤ 1.5 x ULN ALP (Alkaline phosphatase) < 1.5 x ULN Negative bone scan performed no more than 3 months prior to randomisation. Additional CT or ultrasound of thorax, abdomen and/or pelvis is optional. Written informed consent. Exclusion Criteria: Positive bone scan Any distant metastasis detected by CT or ultrasound Patients with a history of previous malignant disease. Exceptions should be made for basal cell carcinoma (BCC) and squamous cell carcinoma of the skin. Exceptions should also be made for curatively treated malignant disease, which has been disease free for the past 5 years. Previous chemotherapy or randomised in SPCG 12/AdPro or SPCG 13/AdRad (SPCG: Scandinavian Prostate Cancer Group). Systemic corticosteroids within 6 months prior to randomisation. Unstable cardiovascular disease, including myocardial infarction, within 6 months prior to randomisation. Active untreated infectious disease, including tuberculosis, MRSA (Methicillin-resistant Staphylococcus aureus. Active gastric ulcer. Known hypersensitivity to Polysorbate 80 (an excipient of docetaxel) Other serious illness or medical condition Symptomatic peripheral neuropathy ≥ CTCAE grade 2. Patients who by altered physical or psychological state not are able to co-operate or participate in the trial.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Andreas Josefsson, PhD

Organizational Affiliation

Univeristy of Gothenburg

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Ingela Turesson, Prof

Organizational Affiliation

Uppsala University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Copenhagen University hospital, Rigshospitalet

City

Copenhagen

Country

Denmark

Facility Name

Kuopio University Hospital

City

Kuopio

State/Province

Kuopio Kuopio

ZIP/Postal Code

70211

Country

Finland

Facility Name

Turku University Hospital

City

Turku

ZIP/Postal Code

20521

Country

Finland

Facility Name

Erasmus Medical Center Rotterdam

City

Rotterdam

ZIP/Postal Code

3015 CE

Country

Netherlands

Facility Name

Sahlgrenska University Hospital

City

Göteborg

ZIP/Postal Code

41345

Country

Sweden

12. IPD Sharing Statement

Links:

URL

http://spcg.se/trials/spcg-14-spcg-14-psa-erect-m0/

Description

SPCG home

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Early Rising PSA Endocrine Treatment Versus Chemo-endocrine Therapy- SPCG14

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