| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| PAIN DUE TO BONE METASTASES |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10049038 |
| E.1.2 | Term | Metastatic bone pain |
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| 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 |
The primary objective of this study is to evaluate the analgesic efficacy of single dose tanezumab 10 mg in combination with opioids (tanezumab 10 mg + opioids) compared with opioids alone (placebo + opioids) in cancer patients with chronic pain due to bone metastases.
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| E.2.2 | Secondary objectives of the trial |
• To characterize the time course of analgesia associated with tanezumab 10 mg when administered in combination with opioids (tanezumab + opioids) compared with opioids alone (placebo + opioids).
• To evaluate opioid consumption, rescue medication use and Opioid-Related Symptom Distress Scale scores of a single dose of tanezumab 10 mg in combination with opioids (tanezumab 10 mg + opioids) compared with opioids alone (placebo + opioids).
• To examine the global assessment scores and the effect on patient function of a single dose of tanezumab 10 mg in combination with opioids (tanezumab 10 mg + opioids) compared with opioids alone (placebo + opioids).
• To characterize tanezumab pharmacokinetics in cancer patients with chronic pain due to bone metastases and treated with opioids.
• To assess the safety and tolerability of single dose tanezumab 10 mg IV in patients with chronic pain due to bone metastases and treated with opioids.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
* Inclusion Criteria:
1. The patient must have prostate or breast cancer that has been diagnosed as having metastasized to bone, and must have moderate to severe pain secondary to the bone metastasis. Radiographic confirmation of bone metastasis (via bone scan, MRI, CT scan or plain x-ray with corresponding bone scan) within 30 days prior to Screening Visit is required. Bone scan confirmation of the bone metastasis is required at Screening Visit if radiographic confirmation of bone metastasis within 30 days prior to screening is lacking. If bone scan at Screening Visit is not clearly consistent with bone metastasis, additional radiographic confirmation (eg, with MRI, CT scan or plain x-ray) is required prior to randomization.
2. The patient is expected to require daily opioid medication throughout the course of the study.
3. The patient is ≥18 years of age.
4. The patient’s weight is ≥45 kg.
5. Female patients must meet one of the following criteria:
a. Female patients of non-childbearing potential: must be postmenopausal, defined as amenorrheic for at least 1 year AND have a serum follicle-stimulating hormone (FSH) level greater than 30 IU/L at Screening; or must be surgically sterile, defined as having had a hysterectomy and/or bilateral oophorectomy;
b. Female patients of child-bearing potential: must not be pregnant or lactating and must be abstinent or use adequate contraception (2 forms of birth control, one of which must be a barrier method).
c. Female patients of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline prior to study medication dosing.
d. Females of child-bearing potential and males must be willing to use approved methods of contraception from commencement of screening procedures until 16 weeks after the dose of study medication.
6. Male patients must also agree that they and their female spouses / partners will use adequate contraception (2 forms of birth control, one of which must be barrier method) or be of non-childbearing potential (ie, is post-menopausal or surgically sterile). Females of child-bearing potential and males must be willing to use approved methods of contraception from commencement of screening procedures until 16 weeks after the dose of study medication.
7. The patient has a Karnofsky Performance Score ≥50% at Screening Visit.
8. The patient has an anticipated life expectancy of ≥6 months at Screening Visit.
9. The patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
10. The patient has provided written informed consent prior to admission to this study.
* Inclusion Criteria (Randomization):
Prior to randomization, the following criteria for pain, daily opioid use, and adverse events must be met during the 3 day Baseline Assessment Period:
1. Total daily dose (fixed component + rescue doses) of the opioid regimen has not changed by more than +20% from Day 1 to Day 2 and from Day 1 to Day 3 of the Baseline Assessment Period.
2. There have been ≤3 IR rescue episodes per day from Day 1 to Day 3 of the baseline Assessment Period for breakthrough pain.
3. The mean value of the “average pain intensity over the last 24 hours” scores from Day 1 to Day 3 of the Baseline Assessment Period must be ≥4 on an 11-point NRS scores range from 0-10).
4. There are no intolerable side effects in the judgment of the patient from Day 1 to day 3 of the Baseline Assessment Period. |
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| E.4 | Principal exclusion criteria |
1. The patient’s pain is related to an oncologic emergency such as bowel obstruction/perforation, brain metastases, epidural metastases, leptomeningeal metastases, fracture or impending fracture of weight-bearing bone or pain related to infection.
2. The patient’s pain is primarily classified as neuropathic or unknown in nature, has resulted from prior cancer therapy, or is not related to a bone metastasis.
3. The patient has received any investigational agent (ie, a medication not approved by the FDA) within 30 days prior to randomization or is scheduled to receive an investigational drug other than tanezumab during the course of this study.
4. The patient is about to begin or has begun systemic therapy for the primary malignancy or for a bone metastasis within 4 weeks of randomization.
5. The patient is currently on a regimen of ongoing therapy for the primary malignancy or for a bone metastasis, which began more than 4 weeks before randomization and is anticipated to change during the treatment period, unless the investigator determines the therapy is unlikely to improve pain. Completion of non-hanging, ongoing therapy begun more than 4 weeks before randomization is allowed.
6. The patient is expected to use any prohibited analgesic specified in the protocol, or to receive any active anticancer therapy throughout the pretreatment and treatment periods that is likely to confound assessment of analgesic efficacy or safety.
7. Receipt of radiopharmaceutical treatment or radiotherapy for treatment of bone metastasis within 4 weeks of randomization.
8. Planned surgical procedure during the duration of the study.
9. The patient uses concurrent adjuvant analgesics such as non-steroidal anti-nflammatory drugs, SNRIs, tricyclic antidepressants, anticonvulsant medication, corticosteroids, or muscle relaxants unless these drugs were started more than 30 days prior to randomization and unless they are maintained at a stable dose.
10. The patient has a history of significant alcohol, analgesic, or narcotic substance abuse within the six months prior to screening.
11. Previous exposure to nerve growth factor or to an anti-nerve growth factor antibody.
12. Patient has a history of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal antibody or IgG-fusion protein.
13. Patient has known hypersensitivity to opioids or an underlying medical condition contraindicating opioid use.
14. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3.0 times the upper limit of normal, or creatinine exceeding 1.7 mg/dL (150 µmol/L) in men or 1.5 mg/dL (133 µmol/L) in women at Screening Visit 1 (each confirmed by a repeat test) or any other laboratory abnormality that in the opinion of the investigator would contraindicate study participation.
15. Presence of hypercalcemia at Screening (Visit 1), defined as albumin-corrected serum calcium concentration of ≥12 mg/dL. If measured albumin is <4.5 gm/dL, corrected calcium (mg/dL) = measured calcium (mg/dL) + 0.8 x (4.5 gm/dl-measured albumin in gm/dl).
16. Presence of drugs of abuse (except for opioids, which are allowed) on urine drug screen.
17. Resting, sitting blood pressure (BP) ≥160 mm Hg in systolic pressure or ≥100 mm Hg in diastolic pressure. If a patient is found to have untreated significant hypertension at screening and antihypertensive treatment is initiated, assessment for study eligibility should be deferred until BP and antihypertensive medication have been stable for at least one month. For patients with previously diagnosed hypertension, antihypertensive medications must be stable for at least 1 month prior to screening for this study.
18. Positive Hepatitis B, Hepatitis C, or HIV tests at screening, indicative of current or past infection.
19. Signs and symptoms of clinically significant cardiac disease.
20. History, diagnosis, or signs and symptoms of clinically significant neurological disease, including peripheral neuropathy.
21. Any significant, uncontrolled chronic disease other than cancer, including psychiatric disorders or cognitive impairment, or any other condition which in the opinion of the investigator would contraindicate study participation, put the patient at increased safety risk or confound interpretation of the results.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is the change from Baseline to Week 6 in the daily average pain intensity measured by the 11-point Pain Intensity Numerical Rating Scale (NRS) where scores range from 0-10. Baseline is defined as the average daily Pain NRS score during the Baseline Assessment Period prior to Randomization (expected to be 3 days). |
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| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| 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 | Information not present in EudraCT |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 19 |
| 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 | Information not present in EudraCT |
| 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 |
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| 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
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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