ILND Surgery Alone or after Chemotherapy with or without Radiation Therapy in Treating Patients with Advanced Penile Cancer

Summary

Objectives

PRIMARY OBJECTIVES:
I. To determine if there is a role for neoadjuvant therapy and if so, whether chemotherapy or chemoradiotherapy produce superior outcomes (either for survival endpoints or for morbidity/quality of life endpoints).
II. To determine the additional survival benefit of prophylactic pelvic lymph node dissection (PLND) given after neoadjuvant chemoradiotherapy or with adjuvant chemoradiotherapy of the pelvic nodes over and above that of chemoradiotherapy alone in patients at high risk of recurrence following inguinal lymph node dissection (ILND).

SECONDARY OBJECTIVES:
I. To determine if neoadjuvant therapy prior to surgery (ILND) can reduce recurrence rates. (International Penile Advanced Cancer Trial [InPACT]-neoadjuvant)
II. To determine which is the more active of neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy. (InPACT-neoadjuvant)
III. To determine the operative/post-operative complication rate following neoadjuvant therapy of both types. (InPACT-neoadjuvant)
IV. To determine if neoadjuvant chemoradiotherapy is feasible in this setting. (InPACT-neoadjuvant)
V. To determine the rate of additional complications for the combination of PLND and chemoradiotherapy. (InPACT-pelvis)

EXPLORATORY OBJECTIVES:
I. To determine the relationship between human papillomavirus (HPV) status and outcome for all groups studied.
II. To determine the impact on quality of life of the (sequential) treatments studied.

OUTLINE:

InPACT-NEOADJUVANT: Patients are randomized to 1 of 3 arms.

ARM A: Patients undergo standard of care ILND surgery.

ARM B: Patients receive paclitaxel intravenously (IV) over 3 hours on day 1, cisplatin IV over 2 hours on days 1-5 or 1-3, and ifosfamide IV over 1 hour on days 2-5 or 1-3. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Approximately 6-12 weeks after day 1 of the last cycle of neoadjuvant chemotherapy, patients undergo ILND surgery.

ARM C: Beginning 4 weeks after randomization, patients receive cisplatin IV and undergo intensity-modulated radiation therapy (IMRT) for 25 fractions over 5 weeks. Approximately 6 weeks after completion of neoadjuvant chemotherapy and IMRT, patients undergo ILND surgery.

InPACT-PELVIS: Patients with pathological high risk are randomized to 1 of 2 arms.

ARM P: Patients undergo PLND surgery. Beginning 8 weeks after PLND surgery, patients who have not received neoadjuvant chemotherapy and IMRT, receive cisplatin IV and undergo IMRT for 25 fractions over 5 weeks.

ARM Q: Patients undergo surveillance at fixed time-points according to local practice. Beginning 8 weeks after ILND surgery, patients who have not received neoadjuvant chemotherapy and IMRT, receive cisplatin IV and undergo IMRT for 25 fractions over 5 weeks.

Patients in all arms also undergo magnetic resonance imaging (MRI) and/or computed tomography (CT) throughout the trial.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.