A Phase I/Ib Trial of the Oral Hedgehog inhibitor, LY2940680, in Combination with Weekly Paclitaxel in Patients with Platinum-Resistant, Recurrent Ovarian Cancer or Recurrent, Advanced, Solid Tumours.
- Conditions
- Ovarian cancer or recurrent, advanced, solid tumours.CancerOvarian cancer
- Registration Number
- ISRCTN15903698
- Lead Sponsor
- HS Greater Glasgow and Clyde
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Stopped
- Sex
- All
- Target Recruitment
- 16
Inclusion criteria of the dose escalation phase:
Histologically or cytologically confirmed advanced solid tumours refractory to standard therapy or for whom weekly paclitaxel is considered, by the investigator, to be an appropriate therapy.
Inclusion criteria of the dose expansion phase:
1. Histologically confirmed high grade serous or G3 endometrioid epithelial ovarian, fallopian tube or primary peritoneal cancer with progressive or recurrent disease (patients with carcinosarcoma are eligible but mucinous, clear cell carcinoma and grade 1 or 2 tumours are not eligible). Progression may be defined radiologically by RECIST 1.1 or by CA125 criteria in combination with clinical symptoms or signs indicative of progression. Asymptomatic rise of CA125 alone will not be defined as progressive disease. Progression of disease must have occurred within 6 months of the last dose of platinum chemotherapy.
2. = 1 previous platinum based chemotherapy. This may have been given in the adjuvant setting.
3. No previous treatment with single agent weekly paclitaxel for relapsed disease. Weekly paclitaxel may have been given in the first line setting if given in combination with platinum chemotherapy.
4. No contra-indication to an image guided biopsy and tumour amenable to image guided biopsy.
5. Measurable or non-measurable disease.
6. Patients must have archival formalin-fixed paraffin-embedded tissue from their original diagnosis available for the purposes of translational research.
7. Patients with synchronous tumours e.g. ovarian and endometrial or history of prior malignancy are eligible provided that there is biopsy evidence that the disease measurable on CT and/or MRI is ovarian in origin
The following inclusion criteria will be required for all patients:
1. Written informed consent
2. Performance status =2 (ECOG)
3. Estimated life expectancy = 3 months
4. Age = 18 years
5. Adequate haematological, renal and hepatic function as defined by:
5.1Haemoglobin (Hb)> 10g/dl
5.2Neutrophil Count> 1.5 x 109/l
5.3Platelets> 100 x 109/l
5.4INR <2 x ULN and prothrombin time and activated partial thromboplastin time < 1.5 x ULN in the absence of therapeutic anticoagulation
5.5Glomerular Filtration rate of > 50 mL/ min (calculated using the Wright formula or measured by EDTA clearance)
5.6Total bilirubin =1.5 x ULN and ALT and AST = 2.5 x ULN
6. No history of grade 2 peripheral neuropathy at any time during prior treatment and no greater than grade 1 residual peripheral neuropathy.
7. No use within the last 7 days of or requirement to continue medications that are strong inhibitors of CYP3A4.
8. No prior treatment with LY2940680 or other Hedgehog pathway inhibitor.
9. Female patients with reproductive potential must have a negative serum pregnancy test within 7 days of trial enrolment and agree to use an effective double barrier method of contraception during and for 6 months after last dose of treatment. Male patients of childbearing potential and their female partner must also agree to use an effective double barrier method of contraception dur
The exclusion criteria are covered by the negative inclusion criteria
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method