Neoadjuvant Chemotherapy for Patients With Squamous Cell Carcinoma of the Penis
Study Details
Study Description
Brief Summary
Primary Objective:
-To evaluate the feasibility and efficacy of multimodality treatment (neoadjuvant chemotherapy prior to extirpative surgery) for clinical stage TXN2-3M0 squamous cell carcinoma of the penis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Before treatment starts, participants will have a complete exam, including blood and urine tests. A CT scan of the abdomen and pelvis will be done. Participants will have a chest x-ray, bone scan, and an EKG (heart test). A special heart function test may also need to be done in some participants. If necessary a biopsy of enlarged lymph node(s) will be obtained prior to treatment.
Blood tests will be repeated once a week during treatment. CT scans of the abdomen and pelvis and a Chest x-ray will be done after 2 treatments with Taxol, Ifosfamide, and Cisplatin. These will also be done before surgery.
The drugs Taxol, Ifosfamide and Cisplatin will be given through a catheter (plastic tube) placed in a vein in the arm or under the collarbone. Taxol will be given over 3 hours the first day of the treatment cycle. To prevent an allergic reaction, before the Taxol is given, the participant will receive three drugs. These are Dexamethasone, Diphenhydramine, and either Cimetidine or Ranitidine.
After Taxol, Ifosfamide will be given over 2 hours every day for the first three days of the treatment cycle. To prevent possible irritation of Ifosfamide to the bladder, participants will also receive Mesna through the plastic catheter. Mesna will be given both before and after Ifosfamide every day. Mesna is not chemotherapy. It is a medication to prevent side effects of Ifosfamide into the bladder.
Every day for the first three days of the cycle, and after Ifosfamide is given, participants will also receive Cisplatin through the catheter at a steady rate over 2 hours, along with Mannitol and salt water to flush the kidneys. This treatment will be given in the hospital and will require staying in the hospital for 3-4 days. It will be repeated for a total of 4 times; once every 21 days, if the participant has high enough numbers of white blood cells and platelets.
Participants may be given injections of G-CSF under the skin once a day for up to 7 days (days 6-12 of the cycle) to bring the white cells up faster after the chemotherapy. This will also lower the risk of severe infections.
After completing 4 treatments of chemotherapy, participants will have blood and urine tests, a chest x-ray to learn the response of the tumor to the chemotherapy. They will also have a CT scan of the abdomen and pelvis. Participants who have a response to the chemotherapy, or show no sign of new spread of the cancer to other parts of the body, will then have surgery. Surgery will be done to remove the tumor. The lymph nodes in the groin will be removed. The pelvic lymph nodes may also need to be removed. How much tissue is removed depends on how far the tumor has spread. The surgeons will explain the specifics of the surgery in a separate consent form.
After completion of the treatment, physical exams, CT scans, chest x-rays, blood tests, and urine tests will be done every 3 months for 2 years. They will then be done every 6 months. These procedures can be done by a physician at M. D. Anderson or by the participant's own doctor. If the participant's doctor does it, the information will need to be forwarded to the doctors at M. D. Anderson. Participants will be expected to come to M. D. Anderson or to their respective participating urologist/medical oncologist at least once every 6 months for a check-up.
This is an investigational study. The FDA has approved Taxol, Ifosfamide, Cisplatin, and Mesna. Up to 40 participants will take part in this study. All will be enrolled at M. D. Anderson.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cisplatin + Ifosfamide + Paclitaxel Cisplatin 25 mg/m^2 IV Days 1-3; Ifosfamide 1200 mg/m^2 IV Days 1-3; Paclitaxel 175 mg/m^2 IV Day 1 |
Drug: Ifosfamide
1200 mg/m^2 By Vein Over 2 Hours on Days 1-3
Other Names:
Drug: Paclitaxel (Taxol)
175 mg/m^2 By Vein Over 3 Hours on Day 1
Other Names:
Drug: Cisplatin
25 mg/m^2 By Vein Over 2 Hours on Days 1-3
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Pathologic Complete Remission (pCR) [restaging with second and fourth 21-day cycles followed by surgery]
Histopathologic assessment of surgical resection to confirm Pathologoic Complete Remission. Complete remission defined as disappearance of all target lesions.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Written informed consent must be obtained from each patient prior to study entry.
-
Age >/= 14 years of age. Life expectancy greater than or equal to 6 months. PS </= 2 (ECOG).
-
Patients with histologically confirmed squamous cell carcinoma of the penis who present with clinical stage (T(subscript)xN(subscript)2-3M(subscript)0) disease based on the 1987-1992 TNM Staging System and meeting the additional clinicopathologic criteria as defined in the protocol (section 3.1).
-
Patients must have adequate physiologic reserve as evidenced by: absolute neutrophil count (ANC) >/= 1,500/mm3(superscript) and platelet count >/= 100,000/mm3. Transaminases </= 2 times the upper limit of normal. Conjugated bilirubin </= 1.5mg/dL. Creatinine clearance (either calculated or measured) of >/= 40ml/minute.
-
No evidence of active ischemia on the EKG and, for patients with significant prior coronary artery disease history, an ejection fraction of more than 40%. No evidence of severe conduction abnormalities on EKG.
Exclusion Criteria:
-
Patients with uncontrolled infection or CNS disease.
-
Distant metastasis (TNM stage M1, i.e., lung, bone, other visceral sites, lymph node metastasis above the aortic bifurcation).
-
Patients with clinically negative inguinal examinations or those with palpable adenopathy not meeting pathological or clinical criteria (i.e., minimal nodal metastasis or false positive inguinal examination).
-
Prior systemic chemotherapy for penile carcinoma.
-
Prior radiation therapy to inguinal or pelvic lymph nodes.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | U.T.M.D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
Investigators
- Principal Investigator: Lance Pagliaro, MD, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- ID99-194
Study Results
Participant Flow
| Recruitment Details | Recruitment period 17-AUG-99 to 15-OCT-08; all participants were recruited at MD Anderson Cancer Center |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Cisplatin + Ifosfamide + Paclitaxel |
|---|---|
| Arm/Group Description | Cisplatin 25 mg/m^2 IV Days 1-3; Ifosfamide 1200 mg/m^2 IV Days 1-3; Paclitaxel 175 mg/m^2 IV Day 1 |
| Period Title: Overall Study | |
| STARTED | 30 |
| COMPLETED | 23 |
| NOT COMPLETED | 7 |
Baseline Characteristics
| Arm/Group Title | Cisplatin + Ifosfamide + Paclitaxel |
|---|---|
| Arm/Group Description | Cisplatin 25 mg/m^2 IV Days 1-3; Ifosfamide 1200 mg/m^2 IV Days 1-3; Paclitaxel 175 mg/m^2 IV Day 1 |
| Overall Participants | 30 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
57.5
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
30
100%
|
| Region of Enrollment (participants) [Number] | |
| United States |
30
100%
|
Outcome Measures
| Title | Number of Participants With Pathologic Complete Remission (pCR) |
|---|---|
| Description | Histopathologic assessment of surgical resection to confirm Pathologoic Complete Remission. Complete remission defined as disappearance of all target lesions. |
| Time Frame | restaging with second and fourth 21-day cycles followed by surgery |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who completed chemotherapy without progression then had surgical resection. |
| Arm/Group Title | Cisplatin + Ifosfamide + Paclitaxel |
|---|---|
| Arm/Group Description | Cisplatin 25 mg/m^2 IV Days 1-3; Ifosfamide 1200 mg/m^2 IV Days 1-3; Paclitaxel 175 mg/m^2 IV Day 1 |
| Measure Participants | 30 |
| Number [participants] |
3
10%
|
Adverse Events
| Time Frame | Nine years and 6 months | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Cisplatin + Ifosfamide + Paclitaxel | |
| Arm/Group Description | Cisplatin 25 mg/m^2 IV Days 1-3; Ifosfamide 1200 mg/m^2 IV Days 1-3; Paclitaxel 175 mg/m^2 IV Day 1 | |
All Cause Mortality |
||
| Cisplatin + Ifosfamide + Paclitaxel | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Cisplatin + Ifosfamide + Paclitaxel | ||
| Affected / at Risk (%) | # Events | |
| Total | 3/30 (10%) | |
| Cardiac disorders | ||
| myocarcial ischemia | 2/23 (8.7%) | 2 |
| Immune system disorders | ||
| allergic reaction | 1/23 (4.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Cisplatin + Ifosfamide + Paclitaxel | ||
| Affected / at Risk (%) | # Events | |
| Total | 13/30 (43.3%) | |
| Blood and lymphatic system disorders | ||
| anemia | 1/30 (3.3%) | 1 |
| Neutropenia | 1/30 (3.3%) | 1 |
| febrile neutropenia | 1/30 (3.3%) | 1 |
| thrombocytopenia | 1/30 (3.3%) | 1 |
| Infections and infestations | ||
| infection | 5/30 (16.7%) | 5 |
| Metabolism and nutrition disorders | ||
| hyperglycemia | 1/30 (3.3%) | 1 |
| Nervous system disorders | ||
| neuropathy motor | 1/30 (3.3%) | 1 |
| Vascular disorders | ||
| deep vein thrombosis | 1/30 (3.3%) | 1 |
| central venous catheter related thrombosis | 1/30 (3.3%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Cherie A. Perez |
|---|---|
| Organization | UT MD Anderson Cancer Center |
| Phone | |
| caperez@mdanderson.org |
- ID99-194