| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Recurrent high grade serous ovarian cancer. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Recurrent High Grade Serous Ovarian Cancer |
|
| 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 | 13.1 |
| 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) |
|
| 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 |
| To evaluate the objective response rate (ORR) of ABT-888 in combination with Temozolomide (TMZ) compared to Pegylated Liposomal Doxorubicin (PLD) alone in subjects with recurrent high grade serous ovarian cancer. |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate progression free survival (PFS), time to progression (TTP), overall survival (OS), 12-month survival rate, 6-month progression free survival rate, duration of response, safety, and tolerability. |
|
| 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 |
Subjects will have the option to participate in the following substudies:
a) Tissue sample collection: Subjects may consent to providing fixed tissue samples taken from a most recent pathological analysis. These tissue samples may help researchers develop a diagnostic test to identify patients most likely to respond to the drug.
b) Fluid aspirates collection: Subjects may consent to providing fixed samples taken from a most recent pathological analysis, if a paracentesis or thoracentesis is performed as standard of care treatment. These samples may help researchers develop a diagnostic test to identify patients most likely to respond to the drug.
c) Genetic sub-study: Subjects may consent to an additional blood draw that will be used for genetic testing to help determine why some ovarian cancer patients may benefit from taking ABT-888 more than others do.
|
|
| E.3 | Principal inclusion criteria |
1. Subject must be at least 18 years of age.
2. Subject must have histologically (or cytologically) confirmed recurrent high grade
serous ovarian, fallopian tube, or primary peritoneal cancer.
3. Subjects must have had at least 1 platinum containing chemotherapy regimen for ovarian cancer and no more than a total of 3 DNA damaging or cytotoxic regimens in the past 5 years. Less than a full dose of a DNA damaging agent, possibly due to reasons such as toxicity or documented allergic reaction will not be counted toward the limit of 3. Previous treatments with biologic agents (including catumaxomab, tigatuzuzumab, abagovomab and bevacizumab), vaccines, immunostimulants, hormonal agents and signal transduction inhibitors (e.g., pazoparib, sorafenib, sunitinib, temsirolimus) are allowed and are not counted towards the limit of 3.
4. Subjects who are resistant to platinum-based therapy; or sensitive to, but are
unable to tolerate platinum-based therapy (i.e., deemed toxic or have a
documented platinum allergy). Subjects must have at least a ≥ 3 month treatment
free interval from the last dose of platinum based therapy. They may have
received other therapy since their last platinum therapy prior to enrolling in this
study.
5. Subject must be eligible to receive PLD treatment (e.g., no allergic reaction,
normal cardiac function).
6. Subject has either:
● Measurable disease, defined as at least 1 unidimensionally measurable lesion
on a CT scan as defined by RECIST version 1.130 OR
● Non-measurable disease with an elevation of serum CA-125 level by GCIG
criteria (baseline sample is at least twice the upper limit of normal and within
2 weeks prior to starting treatment).31
7. Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2.
8. Subject must have adequate hematologic, renal and hepatic function per
institutional normal range as follows:
● Bone Marrow: Absolute neutrophil count (ANC ≥ 1,500/mm3 (1.5 × 109/L);
Platelets ≥ 100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.5 g/dL (1.4 mmol/L);
● Renal function: Serum creatinine ≤ 1.5 × upper limit of normal (ULN) range
OR creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects with creatinine
levels above institutional normal;
● Hepatic function: AST and/or ALT ≤ 2.5 × the ULN range. For subjects with
liver metastases, AST and/or ALT < 5 × the ULN range; Bilirubin ≤ 1.5 × the
ULN range.
● Partial Thromboplastin Time (PTT) must be ≤ 1.5 × the ULN range and INR
< 1.5. Subjects on anticoagulant therapy (such as Coumadin) are allowed on
study and will have an appropriate PTT and INR as determined by the
Investigator.
9. Women of childbearing potential must agree to use adequate contraception (one of the following listed below) prior to study entry, for the duration of study
participation and for 90 days following completion of therapy. Women of
childbearing potential must have a negative serum pregnancy test within 21 days
prior to initiation of treatment and a negative urine pregnancy test on Cycle 1
Day 1 and/or post menopausal women must be amenorrheic for at least 12 months
to be considered of non-childbearing potential.
● Total abstinence from sexual intercourse (minimum one complete menstrual
cycle);
● Vasectomized partner;
● Hormonal contraceptives (oral, parenteral or transdermal) for at least
3 months prior to study drug administration;
● Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal
ring with spermicidal jellies or cream);
● IUD (Intrauterine Device);
10. Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by an
Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to
the initiation of any screening or study-specific procedures. |
|
| E.4 | Principal exclusion criteria |
1. Subject has previously been treated with a PARP inhibitor except as a single dose
from the CTEP Phase 0 (A06-161) study of ABT-888.
2. Subjects who have a history of hypersensitive reaction to the conventional
formulation of doxorubicin HCL, or the components of PLD.
3. Subject has received anticancer agent(s) or an investigational agent within 28 days prior to study drug administration. Subjects who have not recovered to within one grade level (not to exceed grade 2) of their baseline following a significant adverse event or toxicity attributed to previous anticancer treatment are excluded.
4. Subject has undergone major surgery within the previous 28 days prior to study
drug administration.
5. Subject with prior radiotherapy to any portion of the abdominal cavity and pelvis,
unless for the treatment of ovarian, primary peritoneal or fallopian tube cancer.
Subject must have completed radiation at least 28 days prior to study drug
administration and have measurable disease outside the radiation field or
documented progression of lesions within a previously radiated field.
6. Subject with a known history of brain metastases.
7. Clinically significant and uncontrolled major medical condition(s) including but
not limited to:
● Active uncontrolled infection;
● Symptomatic congestive heart failure;
● Unstable angina pectoris or cardiac arrhythmia;
● Psychiatric illness/social situation that would limit compliance with study
requirements.
● Any medical condition, which in the opinion of the Study Investigator, places
the subject at an unacceptably high risk for toxicities.
8. Subject is pregnant or lactating.
9. Subject has been treated or hospitalized for bowel obstruction within 28 days prior to study drug administration.
10. Subject who requires parenteral nutrition or tube feeding and has evidence of
partial bowel obstruction or perforation.
11. The subject has had another active malignancy within the past 5 years except for
any cancer in situ considered cured or non-melanoma carcinoma of the skin.
Questions regarding the inclusion of individual subject are to be directed to the
Abbott Medical Monitor. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The efficacy endpoints include objective response rate (ORR), progression-free survival (PFS), time to progression (TTP), Overall Survival (OS), 12-month survival rate, 6-month PFS rate, duration of response and ECOG performance status. Analyses of these endpoints are described in Section 8.1.2. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Screening to survival follow-up (approx. every 12 weeks or as needed for up to 3 yrs) |
|
| E.5.2 | Secondary end point(s) |
| Progression Free Survival, Time to Progression, Overall Survival, 12-month Survival Rate, 6-month Progression Survival Rate, Duration of Response, Safety and Tolerability |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Screening to survival follow-up (approx. every 12 weeks or as needed for up to 3 yrs) |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| 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) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | No |
| E.8.1.6 | Cross over | Yes |
| 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 | 16 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 16 |
| 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 |
| Argentina |
| Australia |
| Canada |
| Israel |
| New Zealand |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
| The end-of-study is defined as the date of the last subject's last visit, or last follow- up visit, whichever is longer. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| 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 | 3 |
| 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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