Phase I Trial of Weekly Cabazitaxel With Concurrent Intensity Modulated Radiation Therapy and Androgen Deprivation Therapy for the Treatment of Locally Advanced High Risk Adenocarcinoma of the Prostate
Patients with locally advanced high Gleason grade prostate cancer often have local and
metastatic disease progression. To improve on these outcomes, therapy needs to be directed
at controlling the androgen sensitive and insensitive prostate cancer cells in the primary
and metastatic sites. This therapeutic challenge has further prompted the use of combined
modality approaches incorporating chemotherapy and hormonal therapy with radiation aimed at
the intrinsically resistant cells and the micrometastatic disease that are both androgen
sensitive and resistant. High likelihood of occult metastatic disease and existence of
intrinsically castration resistant cells are the main rationales for early institution of
androgen deprivation therapy (ADT) and chemotherapy in prostate cancer.
The rationale for combining chemotherapeutic agents with ADT and radiotherapy in high risk
prostate cancer patients is based on that chemotherapy can enhance radiotherapy and is also
an effective therapy for metastatic castrate resistant disease. Prior studies with weekly
docetaxel with ADT and intensity modulated radiation therapy (IMRT) were safe and feasible
however cabazitaxel is more potent mitotic inhibitor which may further enhance the outcomes
of patients with locally advanced prostate cancer.
Men with locally advanced high risk prostate cancer represent a group of patients for whom
cure is potentially achievable utilizing a multimodality approach. More aggressive treatment
upfront with chemotherapy and ADT would improve the long term disease control. We
hypothesize that Cabazitaxel may be added to radiation therapy safely, and we anticipate
that this novel approach will improve disease control and eventually improve survival for
locally advanced prostate cancer patients.
The safety of the combination of Cabazitaxel with radiation will be established after this
study. Potential efficacy will be determined in the future phase II/III trials. Hypofraction
radiation treatment with shorter duration maybe possible if combined with chemotherapy
modality.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximally Tolerated Dose (MTD) of Cabazitaxel and Intensity Modulated Radiation Therapy (IMRT)
To determine the maximally tolerated dose, or the safety and feasibility, of the concurrent weekly Cabazitaxel and IMRT with androgen deprivation therapy
Weekly during treatment then every 3 months until 2 years after completion of IMRT
Yes
Jianqing Lin, MD
Principal Investigator
Thomas Jefferson University
United States: Food and Drug Administration
11D.243
NCT01420250
September 2011
September 2018
Name | Location |
---|---|
Thomas Jefferson University | Philadelphia, Pennsylvania 19107-6541 |