E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
BRCA germline mutational and Platinum-Resistant or Partially Platinum-Sensitive Recurrent Epithelial Ovarian Cancer. |
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E.1.1.1 | Medical condition in easily understood language |
Ovarian cancer, which has relapsed after previous platinum-containing treatment. The patients have mutations in their BRCA genes. |
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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 | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033130 |
E.1.2 | Term | Ovarian cancer NOS |
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 |
Phase I:
To determine:
• Maximum-tolerated dose (MTD)
• Dose-limiting toxicities (DLT)
• Recommended phase II dose
Phase II:
To investigate the response rate in platinum-resistant and partially platinum sensitive ovarian cancer patients with known BRCA mutations treated with veliparib monotherapy. |
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E.2.2 | Secondary objectives of the trial |
To investigate the clinical safety and toxicity as assessed by NCI CTCAE v4.0
Furthermore, to investigate the PFS and OS in BRCA1/2 positive ovarian cancer patients treated with veliparib.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed epithelial, primary fallopian or primary peritoneal cancer. Stage I-IV.
2. Patients with known germline BRCA1/2 mutations
3. Verified progression by either RECIST criteria and/or GCIG CA125 criteria after previous first line chemotherapy or progression after later lines of cytotoxic treatment.
4. Platinum resistance or partially platinum sensitive disease
- Relapsed within six months of prior first line/later lines of platinum-based therapy or
- Relapsed within six to twelve months of prior first line/later lines of platinum-based therapy
5. Age ≥ 18 years.
6. Performance status 0-2.
7. Measurable disease by RECIST 1.1 or evaluable by CA125 GCIG criteria
8. Adequate bone marrow function, liver function, renal function and coagulation parameters (within 7 days prior to enrollment):
WBC ≥ 3.0 x 10^9/l or neutrophils (ANC) ≥ 1.5 x 10^9/l
Platelet count ≥ 100 x 10^9/l
Hemoglobin ≥ 9.7 g/dl (6 mmol/L)
Serum bilirubin ≤ 1.5 x ULN
Serum transaminases ≤ 2.5 x ULN
Serum creatinine ≤ 1.5 x ULN
9. Written informed consent.
10. Tissue available for BRCAness analysis |
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E.4 | Principal exclusion criteria |
1. Prior treatment with a PARP inhibitor.
2. Platinum-refractory disease (disease that progressed or was stable during prior platinum therapy)
3. Patients who have received (or are planning to receive) treatment with any other investigational agent, or who have participated in another clinical trial within 28 days prior to entering this trial.
4. Pregnant or breast-feeding women. For fertile women a negative pregnancy test at screening is mandatory.
5. Fertile patients not willing to use acceptable and safe methods of contraception during and for 6 months after treatment
6. Other present or previous malignancy except curatively treated cervical cancer stage I, non-melanotic skin cancer or other cancer with minimal risk of relapse.
Curatively treated prior breast cancer is allowed, if no relapse is suspected at time of inclusion.
7. CNS metastasis.
8. History of any chronic medical or psychiatric condition or laboratory abnormality that is not medically controlled or in the opinion of the Investigator may increase the risks associated with study drug administration (e.g. diabetes, cardiac diseases, hypertension, renal or liver disease).
9. Allergy to the ingredients of the study medication. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Toxicity
- Response rates |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every three treatment cycles |
|
E.5.2 | Secondary end point(s) |
• Progression Free Survival (PFS)
• Overall survival (OS)
• Toxicity |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every three treatment cycles |
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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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
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 | No |
E.8.1.1 | Randomised | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 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 |