a phase ib study of the safety, tolerability and efficacy of ly2780301 in combination with gemcitabine

Conditions: Solid Tumors and Non-Hodgkin's Lymphoma

Summary: in the first-in-human, jwaa trial, the ly2780301 displayed a favourable safety profile, a high pharmacokinetic exposure and the ability to decrease ps6. ly2780301 has shown synergistic activity in combination with targeted agents or chemotherapy including gemcitabine. we propose herein to combine ly2780301 with gemcitabine and to treat different tumor types with molecular alterations. this may validate the anti-tumor activity of the ly2780301 and it will increase our knowledge regarding molecular predictors of its efficacy.


Eligibility criteria:
inclusion criteria: 1. dose escalation portion (part 1): have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic disease (including non-hodgkin's lymphoma) with selected molecular alterations and for which no proven effective therapy exists. ; 2. dose confirmation portion (part 2): have histological or cytological evidence of cancer (solid tumor or non-hodgkin's lymphoma) that is advanced and/or metastatic disease: * cohort a: up to 20 patients of any histological type (solid tumor or non-hodgkin's lymphoma) with selected molecular alterations * cohort b: up to 12 patients with ovarian cancer and with selected molecular alterations 1.1 (appendix 4) for solid tumors or by the revised response criteria for malignant lymphoma dose confirmation portion: * measurable disease as defined by recist 1.1 for solid tumors (appendix 4) except ovarian cancer or * response criteria for patients with ovarian cancer who have evaluable but non-measurable disease (appendix 5) or * revised response criteria for non-hodgkins lymphoma (appendix 6) \[4\] are \>/=18 years of age ; \[5\] written informed consent ; \[6\] have adequate organ function including: * hematologic: absolute neutrophil count (anc) \>/=1.5 x 109/l, platelets \>/=100 x 109/l, and hemoglobin \>/=9 g/dl. * hepatic: bilirubin \</=1.5 times upper limits of normal (uln); alanine transaminase (alt) and ast \</=2.5 x uln. (\</=5 x uln if the liver has tumor involvement). * renal: serum creatinine \ 45 ml/min (mdrd) \[7\] ecog performance status \ /=12 weeks ; \[12\] able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels ; exclusion criteria: \[13\] any serious and/or unstable pre-existing medical conditions, psychiatric disorder, or other conditions that could, in the opinion of the investigator, interfere with subject's safety, obtaining informed consent or compliance to the study procedures ; \[14\] have symptomatic cns malignancy or symptomatic brain metastasis. patients with treated cns metastases are eligible provided their disease is radiographically stable and asymptomatic and they are not currently receiving corticosteroids. screening of asymptomatic patients without history of cns metastasis is not required ; \[15\] have pre-existing not controlled cardiovascular disease (including acute coronary syndromes, unstable angina, coronary angioplasty, or stenting within the past 6 months) or any qtc prolongation (defined as a qtc interval \> 480 ms according to friedericia's correction) or other significant ecg abnormalities including 2nd degree av block type ii, 3rd degree av block, or bradycardia (hr \< 50 bpm), or any history of 2nd or 3rd degree block ; \[16\] concomitant treatment prohibited in section 7.8 ; \[17\] pregnancy and breast feeding ;