E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Solid tumor and ErbB2 negative locally advanced or metastatic breast cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
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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 |
For part 1, the primary objective is to assess the safety and tolerability, and to determine the MTD(s) of bosutinib plus capecitabine in patients with locally advanced or metastatic breast cancer or pancreatic cancer or colorectal cancer or cholangiocarcinoma or glioblastoma.
For part 2, the primary objective is to determine the overall response rate (ORR) in women with ER+ and/or PgR+, erbB2- and ER-, PgR- erbB2- locally advanced or metastatic breast cancer.
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E.2.2 | Secondary objectives of the trial |
For part 1, the secondary objectives are to assess the preliminary anti-tumor activity for bosutinib plus capecitabine.
For part 2, the secondary objective is to confirm the MTD(s) identified in part 1 by collecting further data on the safety and tolerability of bosutinib plus capecitabine, to evaluate the pharmacokinetics (PK) of bosutinib plus capeciatbine, to evaluate additional efficacy parameters such as progression-free survival, duration of response and clinical benefit rate (ORR+stable disease longer than 24 wks) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Part 1 only: Subjects with confirmed pathologic diagnosis of advanced breast cancer or pancreatic cancer or colorectal cancer or cholangiocarcinoma or glioblastoma that is not curable with available therapies, for whom bosutinib plus capecitabine is a reasonable treatment option.
• Part 2 only: Subjects with confirmed pathologic diagnosis of locally advanced or metastatic breast cancer, or loco-regional recurrent breast cancer that is not amenable to curative treatment with surgery or radiotherapy.
• Part 2 only: Documented ER+ and/or PgR+/erbB2- (Arm A only) or ER-/PgR-/erbB2- (Arm B only) tumor based on most recently analyzed biopsy, as documented by a local laboratory.
• Part 2 only: Subjects must have received at least one but no more than 2 prior cytotoxic chemotherapy regimens for metastatic breast cancer.
• Parts 1 & 2: At least 1 radiologically measurable lesion as defined by RECIST v1.0.
• Part 2 only: Availability of formalin-fixed paraffin embedded (FFPE) tumor tissue block preferably or alternatively unstained slides for exploratory biomarker analysis.
• Parts 1 & 2: Eastern Cooperative Oncology Group (ECOG) performance status 0-2. |
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E.4 | Principal exclusion criteria |
• Parts 1 & 2: Prior bosutinib, or any other prior Src inhibitor.
• Part 1 only: Prior chemotherapy with capecitabine or 5-fluorouracil (5-FU) for the treatment of metastatic disease is allowed unless patient stopped therapy for toxicity (including but not limited to hand and foot syndrome, grade 3/4 diarrhea, etc).
• Part 2 only: Prior chemotherapy with capecitabine or 5-FU for the treatment of metastatic disease.
• Part 2 only: Prior chemotherapy with capecitabine or 5-FU for adjuvant chemotherapy within the past 12 months
• Part 2 only: erbB2+ breast cancer
• Parts 1 & 2: Cytotoxic chemotherapy, investigational therapy, major surgery or radiation therapy within 14 days of treatment day 1.
• Parts 1 & 2: Bone or skin as the only site of disease.
• Parts 1 & 2: Clinically unstable primary or metastatic central nervous system (CNS) tumors. Subjects with progression of CNS tumors are eligible as long as they have been clinically stable for at least 4 weeks prior to first dose of bosutinib and capecitabine (ie, no significant change in anticonvulsant or corticosteroid doses, mental status, or clinical symptoms).
• Part 2 only: Any other cancer within 5 years before screening with the exception of adequately treated cervical cancer in situ, or adequately treated basal or squamous cell cancer of the skin.
• Parts 1 & 2: Inadequate hepatic/renal/bone marrow function. • Parts 1 & 2: History of clinically significant or uncontrolled cardiac disease. • Parts 1 & 2: Serious concurrent illness. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Response Rate ORR is the proportion of subjects who achieve confirmed tumor response (complete or partial response) per RECIST v1.0.
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 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 | No |
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
| 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 | 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
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Details provided in the protocol. |
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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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |