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

• Sponsor: NCIC Clinical Trials Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT01331083
• Collaborator: Oncothyreon Canada Inc. (Industry)
• Enrollment: 68
• Locations: 10
• Arm: 1
• Actual Duration (Months): 55.8
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: PX-866	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of PX-866 in Patients With Recurrent or Metastatic Castration Resistant Prostate Cancer
• Actual Study Start Date: Apr 4, 2011
• Actual Primary Completion Date: Jan 13, 2015
• Actual Study Completion Date: Nov 27, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PX-866	Drug: PX-866; PX-866: 8mg orally taken daily

Outcome Measures

Primary Outcome Measures

1. Lack of Disease Progression at 12 Weeks [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

Secondary Outcome Measures

1. PSA Response Rate [12 weeks]

   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

2. Objective Response Rate [12 weeks]

   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

3. Change in Circulating Tumour Cell Number During Treatment [12 weeks]

   Proportion of patients with Favorable circulating tumour cell (CTC) conversion (< 5 CTC/7.5 mL)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
2	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
3	BCCA - Cancer Centre for the Southern Interior	Kelowna	British Columbia	Canada	V1Y 5L3
4	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
5	QEII Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 1V7
6	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
7	Cancer Centre of Southeastern Ontario at Kingston	Kingston	Ontario	Canada	K7L 5P9
8	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
9	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
10	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1

Sponsors and Collaborators

• NCIC Clinical Trials Group
• Oncothyreon Canada Inc.

Investigators

• Study Chair: Kim Chi, BCCA Vancouver Cancer Centr
• Study Chair: Sebastien Hotte, Juravinski Cancer Centre at Hamilton Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NCIC Clinical Trials Group
• ClinicalTrials.gov Identifier: NCT01331083
• Other Study ID Numbers: I205
• First Posted: Apr 7, 2011
• Last Update Posted: May 22, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Arm/Group Title	Group A	Group B
Arm/Group Description	Patients with castration resistant prostate cancer, who have received no prior chemotherapy regimens for recurrent disease, treated by PX-866 at 8mg when given orally daily	Patients with castration resistant prostate cancer, who have had PSA progression while receiving abiraterone/prednisonee, treated by PX-866 at 8mg when given orally daily
Period Title: Overall Study
STARTED	43	25
COMPLETED	43	25
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Group A	Group B	Total
Arm/Group Description	Patients with castration resistant prostate cancer, who have received no prior chemotherapy regimens for recurrent disease, treated by PX-866 at 8mg when given orally daily	Patients with castration resistant prostate cancer, who have had PSA progression while receiving abiraterone/prednisonee, treated by PX-866 at 8mg when given orally daily	Total of all reporting groups
Overall Participants	43	25	68
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	70	72	71
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	43 100%	25 100%	68 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	43 100%	25 100%	68 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Canada	43 100%	25 100%	68 100%

Outcome Measures

1. Primary Outcome

Title	Lack of Disease Progression at 12 Weeks
Description	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
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All patients enrolled

Arm/Group Title	Group A	Group B
Arm/Group Description	Patients with castration resistant prostate cancer, who have received no prior chemotherapy regimens for recurrent disease, treated by PX-866 at 8mg when given orally daily	Patients with castration resistant prostate cancer, who have had PSA progression while receiving abiraterone/prednisonee, treated by PX-866 at 8mg when given orally daily
Measure Participants	43	25
Count of Participants [Participants]	14 32.6%	11 44%

2. Secondary Outcome

Title	PSA Response Rate
Description	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
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A	Group B
Arm/Group Description	Patients with castration resistant prostate cancer, who have received no prior chemotherapy regimens for recurrent disease, treated by PX-866 at 8mg when given orally daily	Patients with castration resistant prostate cancer, who have had PSA progression while receiving abiraterone/prednisonee, treated by PX-866 at 8mg when given orally daily
Measure Participants	43	25
Count of Participants [Participants]	1 2.3%	0 0%

3. Secondary Outcome

Title	Objective Response Rate
Description	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
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All patients enrolled

Arm/Group Title	Group A	Group B
Arm/Group Description	Patients with castration resistant prostate cancer, who have received no prior chemotherapy regimens for recurrent disease, treated by PX-866 at 8mg when given orally daily	Patients with castration resistant prostate cancer, who have had PSA progression while receiving abiraterone/prednisonee, treated by PX-866 at 8mg when given orally daily
Measure Participants	43	25
Count of Participants [Participants]	2 4.7%	0 0%

4. Secondary Outcome

Title	Change in Circulating Tumour Cell Number During Treatment
Description	Proportion of patients with Favorable circulating tumour cell (CTC) conversion (< 5 CTC/7.5 mL)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All patients with CTC assessed (not required for Group B patients)

Arm/Group Title	Group A	Group B
Arm/Group Description	Patients with castration resistant prostate cancer, who have received no prior chemotherapy regimens for recurrent disease, treated by PX-866 at 8mg when given orally daily	Patients with castration resistant prostate cancer, who have had PSA progression while receiving abiraterone/prednisonee, treated by PX-866 at 8mg when given orally daily
Measure Participants	25	0
Count of Participants [Participants]	6 14%	0 0%

Adverse Events

Time Frame	6 months
Arm/Group Title	Group A		Group B
Arm/Group Description	Patients with castration resistant prostate cancer, who have received no prior chemotherapy regimens for recurrent disease, treated by PX-866 at 8mg when given orally daily		Patients with castration resistant prostate cancer, who have had PSA progression while receiving abiraterone/prednisonee, treated by PX-866 at 8mg when given orally daily
All Cause Mortality
	Group A		Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/43 (14%)		5/25 (20%)
Serious Adverse Events
	Group A		Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/43 (18.6%)		5/25 (20%)
Gastrointestinal disorders
Diarrhea	3/43 (7%)		0/25 (0%)
Nausea	2/43 (4.7%)		0/25 (0%)
Vomiting	2/43 (4.7%)		0/25 (0%)
Esophageal obstruction	1/43 (2.3%)		0/25 (0%)
General disorders
Fever	0/43 (0%)		1/25 (4%)
Pain	0/43 (0%)		1/25 (4%)
Infections and infestations
Lung infection	2/43 (4.7%)		0/25 (0%)
Urinary tract infection	0/43 (0%)		1/25 (4%)
Injury, poisoning and procedural complications
Hip fracture	0/43 (0%)		1/25 (4%)
Spinal fracture	0/43 (0%)		1/25 (4%)
Fracture	0/43 (0%)		1/25 (4%)
Metabolism and nutrition disorders
Dehydration	1/43 (2.3%)		0/25 (0%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	1/43 (2.3%)		0/25 (0%)
Muscle weakness lower limb	1/43 (2.3%)		0/25 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Other neoplasms benign, malignant and unspecified	1/43 (2.3%)		0/25 (0%)
Nervous system disorders
Peripheral motor neuropathy	1/43 (2.3%)		0/25 (0%)
Renal and urinary disorders
Hematuria	2/43 (4.7%)		0/25 (0%)
Urinary retention	2/43 (4.7%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	Group A		Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/43 (100%)		25/25 (100%)
Eye disorders
Watering eyes	0/43 (0%)		2/25 (8%)
Gastrointestinal disorders
Abdominal pain	8/43 (18.6%)		4/25 (16%)
Constipation	19/43 (44.2%)		14/25 (56%)
Diarrhea	31/43 (72.1%)		18/25 (72%)
Dyspepsia	9/43 (20.9%)		4/25 (16%)
Gastroesophageal reflux disease	3/43 (7%)		1/25 (4%)
Nausea	33/43 (76.7%)		13/25 (52%)
Vomiting	14/43 (32.6%)		11/25 (44%)
Dry mouth	1/43 (2.3%)		4/25 (16%)
Other gastrointestinal disorders	1/43 (2.3%)		5/25 (20%)
General disorders
Chills	3/43 (7%)		1/25 (4%)
Edema limbs	8/43 (18.6%)		6/25 (24%)
Fatigue	30/43 (69.8%)		21/25 (84%)
Fever	3/43 (7%)		3/25 (12%)
Pain	14/43 (32.6%)		3/25 (12%)
Infections and infestations
Other infections and infestations	6/43 (14%)		1/25 (4%)
Injury, poisoning and procedural complications
Bruising	1/43 (2.3%)		3/25 (12%)
Investigations
Weight loss	1/43 (2.3%)		4/25 (16%)
Metabolism and nutrition disorders
Anorexia	21/43 (48.8%)		12/25 (48%)
Musculoskeletal and connective tissue disorders
Back pain	22/43 (51.2%)		14/25 (56%)
Bone pain	6/43 (14%)		8/25 (32%)
Chest wall pain	3/43 (7%)		0/25 (0%)
Generalized muscle weakness	6/43 (14%)		4/25 (16%)
Muscle weakness lower limb	4/43 (9.3%)		4/25 (16%)
Neck pain	4/43 (9.3%)		1/25 (4%)
Pain in extremity	17/43 (39.5%)		6/25 (24%)
Other musculoskeletal and connective tissue disorder	4/43 (9.3%)		0/25 (0%)
Arthralgia	0/43 (0%)		4/25 (16%)
Arthritis	1/43 (2.3%)		3/25 (12%)
Nervous system disorders
Dizziness	4/43 (9.3%)		4/25 (16%)
Dysgeusia	4/43 (9.3%)		5/25 (20%)
Headache	10/43 (23.3%)		7/25 (28%)
Peripheral sensory neuropathy	10/43 (23.3%)		3/25 (12%)
Psychiatric disorders
Anxiety	3/43 (7%)		3/25 (12%)
Depression	3/43 (7%)		1/25 (4%)
Insomnia	8/43 (18.6%)		2/25 (8%)
Renal and urinary disorders
Hematuria	5/43 (11.6%)		2/25 (8%)
Urinary frequency	16/43 (37.2%)		6/25 (24%)
Urinary retention	3/43 (7%)		1/25 (4%)
Urinary incontinence	2/43 (4.7%)		3/25 (12%)
Urinary urgency	0/43 (0%)		3/25 (12%)
Reproductive system and breast disorders
Erectile dysfunction	8/43 (18.6%)		3/25 (12%)
Respiratory, thoracic and mediastinal disorders
Cough	3/43 (7%)		5/25 (20%)
Dyspnea	6/43 (14%)		5/25 (20%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	4/43 (9.3%)		1/25 (4%)
Dry skin	1/43 (2.3%)		2/25 (8%)
Hyperhidrosis	1/43 (2.3%)		2/25 (8%)
Pruritus	0/43 (0%)		3/25 (12%)
Vascular disorders
Hot flashes	10/43 (23.3%)		7/25 (28%)
Hypertension	3/43 (7%)		1/25 (4%)
Hypotension	3/43 (7%)		0/25 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.