HIPROC - Hedgehog Inhibitor and Paclitaxel in Relapsed Ovarian Cancer
Research type
Research Study
Full title
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.
IRAS ID
168273
Contact name
Rosalind (Ros) Glasspool
Contact email
Sponsor organisation
NHS Greater Glasgow and Clyde
Eudract number
2014-004695-37
ISRCTN Number
ISRCTN15903698
Duration of Study in the UK
2 years, 8 months, 1 days
Research summary
Women with platinum-resistant ovarian cancer have a poor prognosis with a median overall survival of only 1 year. Weekly paclitaxel is an established therapy but despite response rates of 30-40%, progression free survival is only 3-5 months. Consequently there is a need for novel, effective therapies. Weekly paclitaxel is well tolerated, making it an appropriate chemotherapy backbone for combination with novel therapies.
The Hedgehog (Hh) signalling pathway is involved in normal development and there is evidence that aberrant activation plays a role in the development of cancers. Activation of the Hh pathway occurs in ovarian cancers and is associated with poor prognosis. It also occurs more frequently in tumours that have recurred or persisted after chemotherapy compared to pretreatment samples from the same patient. In preclinical models, Hh inhibitors inhibit growth of ovarian cancer and maintain responses when given after chemotherapy. Hh inhibitors also increase sensitivity to paclitaxel in taxane resistant ovarian, prostate and breast cancer cell lines. Thus, inhibition of Hh signalling is a potential target for the treatment of ovarian cancer and particularly for treatment of recurrent disease.
LY2940680 is an oral inhibitor of Smoothened, a key component of the Hh pathway. It is safe and tolerable as a single agent with biological effects at doses over 50mg/day and a recommended dose of 400mg/day.
This is a phase I/Ib trial of the combination of weekly paclitaxel given intravenously on day 1, 8 and 15 of a 28 day cycle with continuous oral LY2940860. This will be the first trial to assess this combination. The primary objective is to determine the dose limiting toxicity and maximum tolerated dose in patients with advanced cancers and to establish the safety and tolerability of the combination at the recommended phase 2 dose in patients with recurrent platinum resistant ovarian cancer.REC name
West of Scotland REC 1
REC reference
15/WS/0086
Date of REC Opinion
25 May 2015
REC opinion
Further Information Favourable Opinion