A Phase II Study of PX-866 in Patients With Recurrent or Metastatic Castration Resistant Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

A Phase II Study of PX-866 in Patients With Recurrent or Metastatic Castration Resistant Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01331083
• Other study ID #: I205
• Status: Completed
• Phase: Phase 2
• Start date: September 9, 2011
• Est. completion date: November 27, 2015

Study information

• Verified date: May 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to find out whether the new drug PX-866 will slow the growth of your prostate cancer. The investigators will also watch you carefully for any side effects that PX-866 might cause.

Description:

PX 866 is a new type of drug that inhibits a molecule related to cancer cell growth. While this molecule is also found in normal cells, it is much more active in some cancer cells, so inhibiting the molecule with PX-866 is hoped to slow the growth of cancer cells. Laboratory tests show that it may help slow the growth of prostate cancer in animals, but it is not known whether it will have the same effects in humans. PX-866 has been studied in some cancer patients to find out safe doses that can be given but it has not undergone study in prostate cancer. This study will be the first study of PX-866 in prostate cancer.

Health Canada has not approved the sale or use of PX-866 to treat prostate cancer, although they have approved its use in this clinical trial.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: November 27, 2015
• Est. primary completion date: January 13, 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have a histological or cytological diagnosis of adenocarcinoma of the prostate.

• 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 therapy:

Surgery:

Previous major surgery is permitted provided that it has been at least 14 days prior to patient registration and that wound healing has occurred.

Hormonal Therapy:

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.

Radiation:

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 permitted.

• Laboratory Requirements (must be done within 7 days prior to registration)

Hematology:

Granulocytes (AGC) = 1.5 x 10^9/L Platelets = 100 x 10^9/L

Biochemistry:

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.

Exclusion Criteria:

• 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 protocol.

• 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 compression.

• 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 abiraterone/prednisone.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• PX-866
PX-866: 8mg orally taken daily

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	QEII Health Sciences Centre	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	BCCA - Cancer Centre for the Southern Interior	Kelowna	British Columbia
Canada	Cancer Centre of Southeastern Ontario at Kingston	Kingston	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group	Oncothyreon Canada Inc.

Country where clinical trial is conducted

Canada, 

References & Publications (1)

Hotte SJ, Chi KN, Joshua AM, Tu D, Macfarlane RJ, Gregg RW, Ruether JD, Basappa NS, Finch D, Salim M, Winquist EW, Torri V, North S, Kollmannsberger C, Ellard SL, Eigl BJ, Tinker A, Allan AL, Beja K, Annala M, Powers J, Wyatt AW, Seymour L; Canadian Cance — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lack of Disease Progression at 12 Weeks	Proportion of patients without evidence of progression (objective progression, defined as an increase in sum of diameters of target lesions of at least 20% above the lowest (or baseline) value (minimum of 5 mm increase) OR the appearance of unequivocal increase in non-measurable/non-target disease OR the appearance of new lesions, or PSA progression, defined as a rise in PSA of 25% (minimum 5 ng/ml) above baseline value or nadir, whichever is lowest, and confirmed by a second increasing value at least 3 weeks later) at 12 weeks after start of therapy	12 weeks
Secondary	PSA Response Rate	Proportion of patients with PSA response defined as a > 50% fall in PSA (minimum of 5 ng/ml) from baseline maintained for > 4 weeks without evidence of disease progression otherwise	12 weeks
Secondary	Objective Response Rate	Proportion of patients with objective response defined as 30% decrease in the sum of the longest diameters of the target lesions (partial response) maintained for at least 4 weeks, or complete disappearance of disease and cancer related symptoms (complete response), also maintained for at least 4 weeks	12 weeks
Secondary	Change in Circulating Tumour Cell Number During Treatment	Proportion of patients with Favorable circulating tumour cell (CTC) conversion (< 5 CTC/7.5 mL)	12 weeks