MC1351: PROstate Cancer Medically Optimized Genome Enhanced ThErapy-I (PROMOTE-I)
Rochester, Minn., Jacksonville, Fla., Phoenix/Scottsdale, Ariz.
Trial status: Open for Enrollment
Why is this study being done?
I. To determine whether somatic tumor genome alterations identified in tumor tissue before or after the initiation of abiraterone acetate therapy are associated with a 12-week composite progression free survival (PFS) endpoint.
II. To use tumor tissue obtained prior to the initiation of therapy and from the 12 week biopsy to develop tumor xenografts for mechanistic and functional studies which will determine whether mutations identified in the tumor genome are associated with response to drugs that target the observed mutated genes and/or associated pathways.
I. To determine whether somatic tumor genome alterations identified before or after initiating abiraterone acetate therapy are associated with overall survival.
II. To determine whether somatic tumor genome alterations identified in tumor tissue before or after the initiation of abiraterone acetate therapy are associated with progression free survival (PFS).
Tissue, blood, and urine samples are collected at baseline and after 12-14 weeks of treatment and assessed for circulating tumor cells, genome-wide single-nucleotide polymorphism (SNP), and exome sequencing.
Who is eligible to participate?
- Histological diagnosis of adenocarcinoma of the prostate or documented history in medical records of having received treatment for prostate cancer diagnosis
- Metastatic disease on chest, abdominal, or pelvic computed tomography (CT) and/or bone scan amenable to biopsy
The following laboratory values obtained 14 days prior to registration
1. Hematology: HgB >9.0 gm, ANC ≥ 1500 cells /L, and platelets ≥100,000µ/L
2. Creatinine ≤ 1.5 x upper limit of normal (ULN).
3. SGOT (AST) and SGPT (ALT) ≤ 1.5 x ULN.
4. Castrate serum testosterone level (< 50 ng/dL-or-< 1.7 nmol/L).
Progression while on or after androgen deprivation therapy defined as:
1. Progressive measurable disease: at least a 20% increase in the sum of the longest diameters of measurable lesions over the smallest sum observed or the appearance of one or more new lesions as assessed by imaging during hormone ablation treatment. Measurable lesions are nodal or visceral soft-tissue lesions with nodal lesions ≥ 20 mm in diameter or visceral/soft-tissue lesions ≥ 10 mm in diameter (see Section 11.0).
2. Bone Scan Progression: appearance of 2 or more new lesions on bone scan during hormone ablation treatment.
3. Increasing serum PSA level: Two consecutive increases in PSA levels documented over a previous reference value obtained at least one week apart are required. If the third PSA value is less than the second, an additional fourth test to confirm a rising PSA is acceptable. A minimum starting value of 2.0 ng/mL is required for study enrollment.
NOTE: Androgen deprivation therapy may have included either medical or surgical castration.
- ≥14 days has passed since completing radiotherapy (exception for radiotherapy: ≥ 7 days since completing a single fraction of ≤ 800 cGy to a restricted field or limited-field radiotherapy to non-marrow bearing area such as an extremity or orbit) at the time of registration.
- Patients who may have received systemic chemotherapy or any novel therapeutic CYP-17 inhibitor and/or novel AR inhibitor agents previously for prostate cancer should have received the last dose of the previously administered systemic therapy ≥12 months from the date of registration.
- Provide informed written consent.
- Has recovered from any other therapy-related toxicity to ≤ grade 2, (except alopecia, anemia and any signs or symptoms of androgen deprivation therapy).
- Willing to provide tissue and blood samples for correlative research purposes (see Section 6.2, 14.1, and 17.1 of the protocol)
- ECOG Performance Status (PS) 0, 1 or 2 (Appendix I).
- Patient is considered a candidate for initiating abiraterone acetate and prednisone after failure of hormonal therapy and has no contra-indications to starting this combination Abiraterone acetate and prednisone after failure of hormonal therapy and has no contra-indication to starting this combination as standard of care.
- Patients have stopped any antiandrogen therapy (including bicalutamide) ≤4 weeks prior to first dose of study drug. In addition any other therapies for prostate cancer, other than GnRH analogue therapy, such as progesterone, medroxyprogesterone, progestins (megesterol), or 5-alpha reductase inhibitors (eg, finasteride or dutasteride), must be discontinued ≤2 weeks before the first dose of study drug.
- Use of any of these therapies =< 12 months prior to registration:
- Use of any of the standard therapies for castrate resistant prostate cancer (CRPC) stage =<12 months prior to registration; NOTE: See below for further exclusion details of specific standard therapies
- Initiation of full dose chemotherapy with docetaxel for CRPC stage =<12 months prior to registration is an exclusion criterion
*** Note: Docetaxel for hormone sensitive prostate cancer is not an exclusion criterion
- Use of radium-223 for CRPC stage is an exclusion criteria
- Use of Provenge vaccine for CRPC =< 2 months prior to registration is an exclusion criterion
*** Note: less than 3 doses of Provenge vaccine =< 12 months prior to registration for CRPC is not an exclusion criterion
- Initiation of full dose chemotherapy with mitoxantrone for CRPC stage with-in the previous 12 months is an exclusion criterion
- Use of cabazitaxel chemotherapy =<12 months prior to registration is an exclusion criterion
*** Note: initiation of full dose chemotherapy with cabazitaxel for CRPC stage with-in the previous 12 months is an exclusion criterion
- Use of ketoconazole with steroids =<12 months prior to registration for CRPC stage
*** Note: ketoconazole therapy taken for a time period of =<12 weeks in the 12 month period prior to registration is not an exclusion criterion
- Use of enzalutamide for CRPC stage =<12 months prior to registration is an exclusion criteria use of any experimental or standard of care CYP-17 inhibitors =<12 months prior to registration is an exclusion criteria *** Note: standard of care CRPC therapy with a CYP-17 inhibitor =< 7 days prior to registration is not an exclusion criterion; if taken for 8 days or more it will be counted as an exclusion criterion
- Receiving any intermittent hormonal treatment gonadotropin-releasing hormone (GnRH) analogues and has not yet achieved sub-castrate levels of testosterone (< 50 ng/dl or < 1.7 mmol/L)
- History of or current documented brain metastasis or carcinomatous meningitis, treated or untreated; Note: brain imaging for asymptomatic patients is not required
- Current symptomatic cord compression requiring surgery or radiation therapy
- Note: once successfully treated and there has been no progression, patients are eligible for the study
- Active second malignancy (except non-melanomatous skin or superficial bladder cancer) defined as requiring anticancer therapy or at high risk of recurrence during the study
- Uncontrolled medical conditions such as heart failure, myocardial infarction, uncontrolled hypertension, disseminated on-going coagulopathy, stroke or treatment of a major active infection =< 3 months of registration, as well as any significant concurrent medical illness that in the opinion of the Investigator would preclude protocol therapy
- Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device
- Note: concomitant participation in observational studies is acceptable
- Patients with a global or severe deterioration of health status such that it requires discontinuation of standard of care treatments for CRPC stage without evidence of disease progression =< 12 weeks prior to registration