E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed epithelial, platinum resistant ovarian cancer with negative or unknown BRCA status |
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E.1.1.1 | Medical condition in easily understood language |
Relapsed epithelial, platinum resistant ovarian cancer with negative or unknown BRCA status |
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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 | 10057529 |
E.1.2 | Term | Ovarian cancer metastatic |
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 | 10066697 |
E.1.2 | Term | Ovarian cancer recurrent |
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 | 10033128 |
E.1.2 | Term | Ovarian cancer |
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 response rates (based on either CA125 GCIG or RECIST criteria) of combination topotecan and veliparib (ABT888) in relapsed ovarian cancer with negative or unknown BRCA status. |
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E.2.2 | Secondary objectives of the trial |
To investigate the PFS and OS in ovarian cancer patients treated with topotecan and veliparib.
To investigate the clinical safety and toxicity of the treatment. |
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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.
2. Verified progression by either RECIST criteria and/or GCIG CA125 criteria after previous first line chemotherapy or progression after later lines of cytotoxic treatment.
3. 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-twelve months of prior first line/later lines of platinum-based therapy
4. Age ≥ 18 years.
5. Performance status 0-2.
6. Measurable disease by RECIST 1.1 or CA125 GCIG criteria
7. 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
8. Written informed consent.
9. Tissue available for BRCAness analysis/BRCA mutation analysis. |
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E.4 | Principal exclusion criteria |
1. Prior treatment with a PARP inhibitor.
2. Patients with BRCA1/2 germline mutation.
3. Platinum-refractory disease (disease that progressed or was stable during prior platinum therapy)
4. 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.
5. Previous discontinuation of topotecan treatment due to toxicity, or previous dose reduction because of toxicity
6. Pregnant or breast-feeding. For fertile women a negative pregnancy test at screening is mandatory.
7. Fertile patients not willing to use acceptable and safe methods of contraception during and for 6 months after treatment
8. Other present or previous malignancy except curatively treated cervical cancer stage I, non-melanotic skin cancer or other cancer with minimal risk of relapse. Previous breast cancer is allowed, if disease free follow-up at least five years prior to enrollment.
9. CNS metastasis.
10. History of any chronic medical or psychiatric condition or laboratory abnormality, which 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).
11. Allergy to the ingredients of the study medication. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point is
1 Maximum-tolerated dose (MTD)
2 Dose-limiting toxicities (DLT)
3 Recommended phase II dose
4 Response rates (based on RECIST version 1.1 and GCIG modified CA-125 criteria |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1: Every 4 weeks
2: Every 4 weeks
4: Every 12 weeks |
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E.5.2 | Secondary end point(s) |
• Progression free survival (PFS)
• Overall survival (OS)
• Safety (Adverse Events (AE) and Serious Adverse Events (SAE))
• Translational research including biomarkers expressed in tumor tissue and blood and their potentially predictive or prognostic value.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 6 |
E.8.9.1 | In the Member State concerned days | |