| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic hormone refractory (androgen indepedent) progressive prostate cancer (HRPC) |
|
| E.1.1.1 | Medical condition in easily understood language |
Hormone Refractory Prostate Cancer means that the cancer is no longer
controllable by hormonal therapy. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10062904 |
| E.1.2 | Term | Hormone-refractory prostate cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
•Arm A: To assess the efficacy, in term of PSA response rate, of multiple
doses of CP 751,871 in combination with docetaxel and prednisone in
chemotherapy-naïve patients with HRPC.
•Arm B: To assess the efficacy, in terms of PSA response rate, of CP-
751,871 in combination with docetaxel/prednisone in patients with
HRPC that progress on docetaxel/prednisone alone. |
|
| E.2.2 | Secondary objectives of the trial |
• To assess the safety and tolerability of multiple doses of CP-751,871 in combination with docetaxel and prednisone.
• To assess population PK of CP-751,871 when used in combination with docetaxel
and prednisone. • To evaluate the effect of CP-751,871 in combination with docetaxel
and prednisone on biomarkers. • To test for the occurrence of HAHA response to CP-751,871. • The feasibility of performing quality of life and pain questionnaires in
this patient population will be investigated. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Histologically confirmed adenocarcinoma of the prostate (a new
diagnostic biopsy
is not required).
2.Evidence of metastatic disease either on bone or CT scans.
3.At least 18 years old.
4.PSA above 5 ng/mL. 5.Progressive disease after at least 1 hormonal treatment (orchiectomy,
estrogens, LHRH therapy etc.) with documented testosterone levels less
than 50 ng/dL (equivalent to 1.7 nmol/L) and progressive disease
defined by the following:
- An increase in PSA>50% over nadir value on hormonal therapy
measured on 3 successive occasions at least 1 week a part. If the third
measurement is lower than the second, a fourth measurement will be
taken. Only if the fourth measurement is higher than the second, the
patient will be enrolled in the study.
- Disease progression as defined by RECIST
- Two or more new bone lesions
6.Concurrent use of LHRH agonist is required if the patient has not been
surgically castrated.
7.Eastern Cooperative Oncology Group (ECOG) performance status of 0,
1 or 2 determined within 2 weeks prior to enrollment (Appendix E).
8.Recovered to CTCAE <Grade 1 or deemed irreversible from the effects
of prior cancer therapy. CTCAEs > Grade 1 that are not considered a
safety risk by the sponsor and investigator will be allowed.
9.Stable level of pain for at least one week before enrollment.
10.Absolute neutrophil count of >1.5 x 109/L and platelets >100 x
109/L.
11.Adequate blood chemistry parameters as defined by:
- Creatinine <1.7 mg/dL (equivalent to 151 micromol/L). If creatinine is
>1.7 mg/dL, the calculated creatinine clearance must be >40 ml/min
from the Cockcroft Gault or MDRD formulas (Appendix D).
- Bilirubin <ULN.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
<1.5 x ULN
12. Hemoglobin >10 g/dL.
13. Written and voluntary informed consent understood, signed and
dated. |
|
| E.4 | Principal exclusion criteria |
1.Prior chemotherapy or radioisotopes treatment for prostate cancer.
2.Prior anti IGF 1R and antibody based investigational therapies. Other
investigational therapies (targeted or vaccine), unless otherwise agreed
by investigators and sponsor, will require 4 weeks wash out period
before enrollment.
3.Antiandrogen therapy (eg, flutamide) for primary cancer within 4
weeks prior to enrollment (6 weeks in the case of bicalutamide,
nilutamide or other long acting anti androgens).
4.Radiation therapy to more than 25% of the bone marrow.
5.Local radiation within 2 weeks of enrollment.
6.Surgery within 4 weeks prior to study enrollment or not fully recovered
from side effects of previous procedures.
7.Use of products known to affect PSA levels within 4 weeks of
enrollment (eg, PC Calm, PC Plus, PC SPES, finasteride).
8.A serious uncontrolled medical disorder or active infection that would
impair the ability to receive study treatment.
9.Significant active cardiac disease including: uncontrolled high blood
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pressure (ie, systolic blood pressure >160 mmHg, diastolic blood
pressure >95 mm Hg), unstable angina, deep venous thrombosis,
pulmonary embolism, cerebro vascular attack, valvular disease,
congestive heart failure, myocardial infarction within the previous 6
months, or serious cardiac arrhythmias.
10.Subjects who are receiving chronic high dose immunosuppressive
steroid therapy. Use of high dose corticosteroids within 2 weeks prior to
enrollment (≥100 mg prednisone per day or >40 mg dexamethasone per
day). Previous steroid treatment is allowed but must be stopped at
enrollment. Low dose steroid use for the control of nausea and vomiting
(eg, dexamethasone 20 mg/day for up to 5 days) will be allowed.
Topical steroid use is permitted. Inhaled steroids are permitted. Use of
dexamethasone as pre medication is not an exclusion criterion.
11. Known severe hypersensitivity reactions to docetaxel or other drugs
formulated in polysorbate 80.
12. Medical contraindication to any of the docetaxel pre medications.
13. Neuropathy greater than Grade 1 or evidence of unstable
neurological symptoms within 4 weeks prior to enrollment.
14. Brain metastasis. Unevaluated central nervous system (CNS)
symptoms suggestive of brain metastases within 2 weeks prior to
enrollment. CNS symptoms must be evaluated with a computerized
tomography (CT) scan or magnetic resonance imaging (MRI).
15. Dementia or significantly altered mental status that would limit the
understanding or rendering of informed consent and compliance with the
requirements of this protocol.
16. Subjects with reproductive potential who are not using adequate
barrier methods on treatment.
17. Active malignancy other than prostate cancer within the past five
years with the exception of non melanoma skin cancer (basal or
squamous-cell skin cancer).
18. Subjects who have been admitted to an institution by virtue of an
order issued by either the judicial or administrative authorities. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
POC1 (200 pts 6 cycles) done on 02Jul10
POC 2 (200 pts 40 crossovers) done on 21Sep10 |
|
| E.5.2 | Secondary end point(s) |
Safety and tolerability;
Population PK parameters of CP-751,871;
HAHA;
Total number of circulating tumor cells (CTCs) and CTCs expressing
IGF-1R;
Pain measured by the Modified Brief Pain Inventory-Short Form (BPIsf
modified Pfizer) and Quality of life measured by the Functional
Assessment of Cancer Treatment-Prostate (FACT-P). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| POC 3 (200 pts 15 cycles) done on 21Sep10 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 9 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| Germany |
| Netherlands |
| Spain |
| Switzerland |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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