Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Ifosfamide · 2 trials · 12 indications
The primary outcome measure that will be measured for all trial patients is survival time. This is defined in whole days as the time from the date of randomisation to the date of death from any cause; for those who have not been reported as dead at the time of analysis, the survival time will be censored at the date of last follow-up.
| Arm | Type | Description |
|---|---|---|
| Arm A - Standard Surgery (ILND) | ACTIVE_COMPARATOR | Part of randomisation 1. The total treatment duration (Inguinal Lymph Node Dissection (ILND)) is estimated to be over 1 day for those patients allocated to Arm A - standard surgery. |
| Arm B - neoadjuvant chemotherapy | EXPERIMENTAL | Part of randomisation 1. Patients will receive up to 4 cycles of Paclitaxel, Ifosfamide, and Cisplatin (TIP). Administration on an outpatient basis: Paclitaxel 175 mg/m2, day 1, Ifosfamide 900 mg/m2, days 2-5, Cisplatin 15 mg/m2, days 1-5 Administration on an inpatient basis: Paclitaxel 175 mg/m2, day 1, Ifosfamide 1200 mg/m2, days 1-3, Cisplatin 25 mg/m2, days 1-3 |
| Arm C - neoadjuvant chemoradiotherapy | EXPERIMENTAL | Part of randomisation 1. Radiotherapy dose is 45Gy in 25 fractions over 5 weeks using 6-10 MV photons to all regions. Concurrent cisplatin 40mg/m2 will be given weekly, subject to GFR\>45mls/min. |
| Arm P - prophylactic PLND | EXPERIMENTAL | Part of randomisation 2. Prophylactic pelvic lymph node dissection (PLND) - The total treatment duration is estimated to be over 1 day. Patients who have NOT received neoadjuvant chemoradiotherapy will receive adjuvant chemoradiotherapy: Cisplatin 40mg/m2 will be given weekly, subject to GFR\>45mls/min. Groin: One or both groins may be boosted up to 54Gy in 25 fractions. An IMRT boost of up to 57 Gy can be given to recurrent or residual macroscopic tumour Pelvis: the dose is limited to 45Gy unless IMRT is available. An IMRT boost of up to 54Gy in 25 fractions is applied to: 1. Any macroscopic tumour or pathological lymph nodes 2. Electively to external iliac nodes in patient with high disease burden Patients who have had neoadjuvant chemoradiotherapy will have prophylactic PLND alone. |
| Arm Q - Surveillance no prophylactic PLND | NO_INTERVENTION | no prophylactic PLND Part of randomisation 2. For patients who have NOT received neoadjuvant chemoradiotherapy: Groin: One or both groins may be boosted up to 54Gy in 25 fractions. An IMRT boost of up to 57 Gy can be given to recurrent or residual macroscopic tumour Pelvis: the dose is limited to 45Gy unless IMRT is available. An IMRT boost of up to 54Gy in 25 fractions is applied to: Any macroscopic tumour or pathological lymph nodes Electively to external iliac nodes in patient with high disease burden |
| Arm A: TIP | OTHER | Patients will receive treatment for 4 cycles administered every 21 days. Cycles 1-4 (1 cycle = 21 days) * paclitaxel 250 mg/m\^2 IV over 24 hours on Day 1 including premedication as defined in the protocol (eg, dexamethasone, diphenhydramine and H2 blocker) * ifosfamide 1500 mg/m\^2 IV daily on Days 2-5 with mesna protection as defined in the protocol * cisplatin 25 mg/m\^2 IV daily on Days 2-5 * pegylated G-CSF 6 mg subcutaneous on Day 6 or 7 or G-CSF as defined in the protocol on Days 6-18 Patients may commence with each Arm A cycle provided they meet the criteria as defined in the protocol. |
| Arm B: TI-CE | OTHER | Patients will receive treatment for a total of 5 cycles. Cycles 1-2 (1 cycle = 14 days) * paclitaxel 200 mg/m\^2 IV over 3 hours on Day 1 including premedication as defined in the protocol (eg, dexamethasone, diphenhydramine and H2 blocker) * ifosfamide 2000 mg/m\^2 IV daily on Days 1-3 with mesna protection as defined in the protocol * G-CSF 10 µg/kg subcutaneously on Days 3-15 (cycle 1) and Days 3-14 (cycle 2) or pegylated G-CSF 6 mg subcutaneous on Day 4 or 6 (cycle 1) and Day 4 or 5 (cycle 2) * leukapheresis every 14 days, if there is an inadequate number of CD34+ cells/kg collected in cycle 1 Cycles 3-5 (1 cycle = 21 days) * carboplatin daily on Days 1-3 * etoposide 400 mg/m\^2 daily on Days 1-3 * stem cell reinfusion on day 5 * pegylated G-CSF 6 mg subcutaneously or G-CSF at approximately 5 µg/kg daily on Days 5-15 Patients may commence with each Arm B cycle provided they meet the criteria as defined in the protocol. |
| Name | Type | Description |
|---|---|---|
| ILND - Inguinal Lymph Node Dissection | PROCEDURE | Surgery to remove the lymph nodes in the groin near to where the cancer first appeared. |
| Paclitaxel | DRUG | Dose 175mg/m2 as part of TIP regimen. |
| Ifosfamide | DRUG | Dose 900mg/m2 as part of TIP regimen. |
| Cisplatin | DRUG | Dose 15mg/m2 as part of TIP regimen (neoadjuvant chemotherapy arm) Dose 40mg/m2 for use concurrently with raditotherapy (chemoradiotherapy arm) |
| Intensity modulated radiation treatment (IMRT) | RADIATION | Treatment with very high energy X-rays (radiotherapy). |
| Prophylactic PLND - pelvic lymph node dissection | PROCEDURE | Surgery to remove the lymph nodes deeper in the pelvis, further away from where the cancer first appeared, that are at high risk of harbouring cancer. |
| pegylated G-CSF | DRUG | IV |
| G-CSF | DRUG | IV |
| carboplatin | DRUG | IV |
| etoposide phosphate | DRUG | IV |
| stem cell reinfusion | PROCEDURE | surgical procedure |
Inclusion Criteria: 1. Written informed consent 2. Measurable disease as determined by RECIST (version 1.1) criteria; 3. Histologically-proven squamous cell carcinoma of the penis, 4. Stage: * any T, N1 (i.e. a palpable mobile unilateral inguinal lymph node), M0 or; * any T, N2 (i.e. palpabl...
Ifosfamide is an investigational small molecule being studied in oncology for squamous cell carcinoma of the penis, usual type, and germ cell tumors. It is currently in Phase 3 clinical development and has not been approved by the FDA.
Ifosfamide is being developed by United Therapeutics Corporation, which trades under the ticker UTHR. The company is conducting Phase 3 trials for this investigational oncology drug.
Ifosfamide is in Phase 3 clinical development. It is an investigational drug, meaning it has not received FDA approval and is still being studied in clinical trials for squamous cell carcinoma of the penis and germ cell tumors.
Ifosfamide is being studied in two Phase 3 trials. NCT02305654 is recruiting 200 male patients with squamous cell carcinoma of the penis in the US and UK. NCT02375204 is active but not recruiting 420 male patients with germ cell tumors across multiple countries.
Ifosfamide is a small molecule oncology drug. Its specific molecular target has not been disclosed in the available information, so its mechanism of action is not detailed here.