A Phase II Study of PX-866 in Patients With Recurrent or Metastatic Castration Resistant Prostate Cancer
- Patients must have a histological or cytological diagnosis of adenocarcinoma of the
- All patients must have formalin fixed paraffin embedded tissue (from their primary or
metastatic tumour) available for translational studies.
- Presence of clinically and/or radiologically documented disease (measureable or
non-measurable). All radiology studies must be performed within 28 days prior to
registration (within 35 days if negative).
- Androgen ablation must include either medical or surgical castration. If the patient
is receiving medical androgen ablation, a castrate level of testosterone (< 1.7
nmol/L) must be present.
- Patients must have metastatic or locally recurrent disease, for which no curative
therapy exists and for which systemic therapy is indicated.
- No prior chemotherapy regimens for recurrent disease
For Part A, patients must have progression defined as:
PSA Progression: A rising PSA, while receiving androgen ablative therapy, with 2
subsequent rises over a reference value (not necessarily consecutively), measured a
minimum of one week apart. The PSA that confirms progression must have a value of ≥ 5
ng/ml and must be performed no longer than 7 days prior to trial registration.
OR Radiological Progression: defined as the development of new metastatic lesions with a
stable or rising PSA.
Patients entered to Part B of the study (after 2nd stage of accrual completed) must have a
rise in their PSA while on abiraterone/prednisone continuing at time of registration (≥
25% higher from baseline or nadir, whichever is lowest).
- The PSA must be ≥5 ng/ml at the time of study entry.
- ECOG performance of 0, 1 or 2.
- Age ≥ 18 years of age.
Previous major surgery is permitted provided that it has been at least 14 days prior to
patient registration and that wound healing has occurred.
Prior hormone therapy is required. Patients must be hormone refractory and have
discontinued anti-androgens for at least 4 weeks prior to study entry (at least 6 weeks
for bicalutamide). Therapy with LHRH agonist must continue for those prostate cancer
patients already receiving this treatment at the time of enrollment. If the patient has
discontinued the LHRH agonist, this must be restarted (if not surgically castrated) and
the castrate level of testosterone must be present. Prior therapy with CYP17 inhibitors
(e.g. abiraterone, ketoconazole) or novel anti-androgens (e.g. MDV3100) is permitted.
Part B: Patients must be hormone refractory and have discontinued anti-androgens for at
least 4 weeks prior to study entry (at least 6 weeks for bicalutamide). Therapy with LHRH
agonist must continue for those prostate cancer patients already receiving this treatment
at the time of enrollment. If the patient has discontinued the LHRH agonist, this must be
restarted (if not surgically castrated) and the castrate level of testosterone must be
present. All patients must currently be receiving abiraterone.
Prior external beam radiation is permitted provided a minimum of 2 weeks has elapsed
between the last dose and enrollment to the trial. Exceptions may be made for low dose,
non-myelosuppressive radiotherapy after consultation with NCIC CTG. Prior strontium is not
- Laboratory Requirements (must be done within 7 days prior to registration)
Granulocytes (AGC) ≥ 1.5 x 10^9/L Platelets ≥ 100 x 10^9/L
Serum creatinine ≤ 1.5 x UNL Total bilirubin ≤ 1.5 x UNL ALT and AST ≤ 1.5 x UNL Glucose ≤
8.9 mmol/L (≤ Grade 1) PSA ≥ 5ng/mL
-Patient consent must be appropriately obtained in accordance with applicable local and
regulatory requirements. Each patient must sign a consent form prior to enrollment in the
trial to document their willingness to participate.
Patients who cannot give informed consent (i.e. mentally incompetent patients, or those
physically incapacitated such as comatose patients) are not to be recruited into the
study. Patients competent but physically unable to sign the consent form may have the
document signed by their nearest relative or legal guardian. Each patient will be provided
with a full explanation of the study before consent is requested.
- Patients must be accessible for treatment and follow-up. Patients registered on this
trial must be treated and followed at the participating centre. This implies there
must be reasonable geographical limits (for example: 2 hour's driving distance)
placed on patients being considered for this trial. Investigators must assure
themselves that the patients registered on this trial will be available for complete
documentation of the treatment, adverse events, response assessment and follow-up.
- In accordance with NCIC CTG policy, protocol treatment is to begin within 5 working
days of patient registration.
- Patients with a history of other malignancies, except for adequately treated
non-melanoma skin cancer or solid tumours curatively treated with no evidence of
disease for >=3 years.
- Known HIV-positive patients.
- Uncontrolled diabetes mellitus.
- Patients with upper gastrointestinal or other conditions that would preclude
compliance or absorption of oral medication are not eligible.
- Patients with active or uncontrolled infections, or with serious illnesses or medical
conditions which would not permit the patient to be managed according to the
- Patients are not eligible if they have a known hypersensitivity to the study drug(s)
or their components.
- Patients with history of central nervous system metastases or untreated spinal cord
- Patients who have had prior treatment with a PI3 kinase inhibitor.
- Men who are not sterile unless they use an adequate method of birth control.
- Patients enrolled to Part B must be suitable for continued therapy with