E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Malignant Melanoma |
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E.1.1.1 | Medical condition in easily understood language |
Advanced stage melanoma that has spread to other parts of the body (metastatic malignant melanoma). |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025671 |
E.1.2 | Term | Malignant melanoma stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027480 |
E.1.2 | Term | Metastatic malignant melanoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 compare the following regimens with respect to antitumor activity in patients who are previously untreated with cytotoxic chemotherapy for metastatic malignant melanoma:
• ABI-007 150 mg/m2 Days 1, 8, and 15 every 4 weeks
• Dacarbazine 1000 mg/m2 every 3 weeks |
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E.2.2 | Secondary objectives of the trial |
• Compare the safety and tolerability of the 2 treatments;
• Evaluate pharmacokinetic parameters of ABI-007; and
• Compare SPARC and other molecular biomarkers with efficacy outcomes. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Tumor Biomarkers and Clinical Outcomes in Patients with Metastatic Malignant Melanoma, 15 April 2009.
This sub-study details the collection and preparation of specimens to be processed for SPARC biomarker analyses in this study.
The exploratory analyses of other molecular biomarkers in Phase III trials of ABI-007 will be performed to validate their correlation with clinical outcomes utilising only a small subset of the samples (approximately 150 patients). Complete exploratory biomarker analyses of all patient samples will only be performed upon positive outcome of subset analyses. This represents a unique opportunity to obtain valuable information, given the large number of patients who will be participating. These investigations are described as a secondary objective of the main study. |
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E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed malignant melanoma with evidence of metastasis (Stage IV).
2. No prior cytotoxic chemotherapy for metastatic malignant melanoma is permitted. No prior adjuvant cytotoxic chemotherapy is permitted. Prior treatment with kinase inhibitors or cytokines is permitted. Prior adjuvant therapy with interferon, GM-CSF and/or vaccines is permitted. Prior treatments should be completed 4 weeks prior to enrollment in the study.
3. Male or non-pregnant and non-lactating female, and ≥ 18 years of age. If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative serum pregnancy test (ß-hCG) within 72 hours prior to first study drug administration. If sexually active, the patient must agree to utilize contraception considered adequate and appropriate by the investigator during the period of administration of dacarbazine or ABI-007. In addition, male and female patients must utilize contraception after the end of treatment as recommended in the product’s Summary of Product Characteristics or Prescribing Information provided in the study manual.
4. History of malignancy in the last 5 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone and have been continuously disease-free for at least 5 years.
5. Radiographically-documented measurable disease (defined by the presence of at least 1 radiographically documented measurable lesion).
6. Patient has the following blood counts at Baseline:
- ANC ≥ 1.5 x 109 cells/L;
- platelets ≥ 100 x 109 cells/L;
- Hgb ≥ 9 g/dL.
7. Patient has the following blood chemistry levels at Baseline:
- AST (SGOT), ALT (SGPT) ≤ 2.5x upper limit of normal range (ULN); ≤ 5.0 xULN if hepatic metastases present;
- total bilirubin ≤ ULN;
- creatinine ≤ 1.5 mg/dL.
- LDH ≤ 2.0 x ULNa
8. Expected survival of > 12 weeks.
9. ECOG performance status 0-1.
10. Patient or his/her legally authorized representative or guardian has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent form prior to participation in any study-related activities. |
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E.4 | Principal exclusion criteria |
1. History of or current evidence of brain metastases, including leptomeningeal involvement.
2. Patient has pre-existing peripheral neuropathy of NCI CTCAE Scale of Grade ≥ 2.
3. Prior radiation to a target lesion is permitted only if there has been clear progression of the lesion since radiation was completed.
4. Patient has a clinically significant concurrent illness.
5. Patient is, in the investigator’s opinion, unlikely to be able to complete the study through the End of Study (EOS) visit.
6. Patient is currently enrolled, or will enroll in a different clinical study in which investigational therapeutic procedures are performed or investigational therapies are administered while participating in this study. Marker studies or studies evaluating biological correlates are permitted.
7. Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug.
8. Any known severe hypersensitivity reaction to any substances included in the investigational product or comparator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is progression-free survival (PFS) based on a blinded radiology assessment of response using RECIST response guidelines. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The final analysis of independently-assessed PFS will be conducted based on all data through 30 June 2012. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Final analysis of overall survival after 417 events |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
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 |
Australia |
Canada |
United States |
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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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LPLV is the definition of end of trial. However, after the last visit of each patient overall survival status is to be monitored on a monthly basis for 6 months and then every 3 months thereafter, for a total of 2 years. |
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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 | 2 |
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 |