Squamous Cell Carcinoma of the Penis Clinical Trial
— PENILANEOfficial title:
A Randomized Phase II Study to Evaluate the Efficacy and Safety of Cetuximab in Metastatic Penile Carcinoma
The purpose of this study is to evaluate the efficacy and safety of Cetuximab in metastatic penile carcinoma
Status | Withdrawn |
Enrollment | 0 |
Est. completion date | February 2016 |
Est. primary completion date | February 2016 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
INCLUSION CRITERIA : - Male older than 18 years-old, - Squamous cell carcinoma of the penis of clinical stages N3 and/or M1, - Central Histological confirmation of diagnosis of wild-type K-ras penis cancer (histological documentation of the mutational status prior to each patient's registration). Nota Bene: an archival tumor sample must be available. - At least one measurable lesion according to the RECIST version 1.1. In case of relapsing patient, documented progression as per RECIST version 1.1, - Eastern Cooperative Oncology Group (ECOG) Performance Status = 2, - Life expectancy = 6 months, - Adequate organs functions defined as the following (transfusion is not allowed within 7 days prior to lab test performed to assess the eligibility): - Hemoglobin = 9 mg/dL, - Absolute Neutrophils Count = 1,5 Gi/l, - Platelets = 100 Gi/l, - Creatinine = 1,5 x Upper Limit of Normal (ULN) and Creatinine clearance = 60 ml/min (calculated with Cockcroft formula or Modification of Diet in Renal Disease (MDRD) formula for patients older than 65 years old) - Aspartate aminotransferase (ASAT) and Alanine aminotransferase (ALAT) = 2,5 x ULN (= 5 x ULN in presence of liver metastasis) - Total bilirubin = 1,5 x ULN, - Willingness to use effective contraceptive method during the whole treatment period and up to 4 months after the last study drug administration, - Affiliated to the French social security system, - Subjects must provide written informed consent prior to perform any study-specific procedures or assessments and must be willing to comply with treatment and follow up. EXCLUSION CRITERIA : - Symptomatic metastases of Central nervous system (CNS) requiring or having required steroids or enzyme-inducing anticonvulsants within 4 weeks before inclusion, - Previous treatment with paclitaxel, or ifosfamide, or cetuximab, or any monoclonal antibody, and or any drug targeting EGF Receptor, - Local and/or resectable disease, - Prior history of other malignancies other than penis cancer (except for basal cell or squamous cell carcinoma of the skin and superficial bladder carcinoma) unless the subject has been free of the disease for at least 3 years, - No resolution of specific toxicities related to any prior anti-cancer therapy to Grade =1 according to the CTCAE v.4.0 (except lymphopenia and alopecia), - Active peripheral or motor neuropathy of any CTCAE grade and due to any cause, - Known hypersensitivity or allergy or contraindication to at least one of the study drugs - In case of previous chemotherapy, wash out period of less than 5 half-lives of treatment before study entry, - Clinically significant cardiovascular disease including: - Myocardial infarction within 3 months, - Congestive heart failure of the New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening Left Ventricular Ejection Fraction (LVEF) assessment = 45%, - Prolonged QT interval defined as screening corrected QT interval (QTc) > 470 ms (Fridericia correction formula), - History of clinically significant ventricular arrhythmia (e.g., ventricular tachycardia, ventricular fibrillation, ...), - History of Mobitz II 2nd degree or 3rd degree heart block without a permanent pacemaker in place, - Hypotension (systolic BP < 86 mmHg) or bradycardia with a heart rate < 50 bpm, - Uncontrolled hypertension as indicated by a resting systolic BP > 170 mmHg or diastolic BP > 105 mmHg despite an optimal treatment, - Major surgery or radiation therapy within 4 weeks prior first study drug administration or already planned during the study, - Any pulmonary, thyroid, renal, hepatic severe/uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol, - Active uncontrolled viral, fungal or bacterial infection, - Patient who cannot abstain from vaccine against yellow fever, prophylactic use of phenytoin or derivate, or any drug which can strongly interfere with the sub-units 2C8 and/or 3A4 of the cytochrome P450 (Cf. appendix 5) Nota Bene: in case of poor interference with these sub-units, treatments with a narrow therapeutic index should be avoided. - Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements (participants must agree to refrain from substance abuse use during the entire course of the study), - Concomitant participation to another clinical trial with active agent during the study (concomitant non interventional study will be allowed). |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
France | Institut Bergonié | Bordeaux | Gironde |
France | Centre Léon Bérard | Lyon | Rhône |
France | Institut Paoli Calmettes | Marseille | Bouches du Rhône |
France | APHP Hôpital Saint Louis | Paris | Ile de France |
France | Institut Curie | Paris | Ile de France |
France | CHRU Strasbourg | Strasbourg | Bas Rhin |
France | Institut Claudius Regaud | Toulouse | Haute Garonne |
Lead Sponsor | Collaborator |
---|---|
Centre Leon Berard |
France,
Andersson P, Kolaric A, Windahl T, Kirrander P, Söderkvist P, Karlsson MG. PIK3CA, HRAS and KRAS gene mutations in human penile cancer. J Urol. 2008 May;179(5):2030-4. doi: 10.1016/j.juro.2007.12.040. Epub 2008 Mar 19. — View Citation
Barnholtz-Sloan JS, Maldonado JL, Pow-sang J, Giuliano AR. Incidence trends in primary malignant penile cancer. Urol Oncol. 2007 Sep-Oct;25(5):361-7. Erratum in: Urol Oncol. 2008 Jan-Feb;26(1):112. Guiliano, Anna R [corrected to Giuliano, Anna R]. — View Citation
Baselga J, Pfister D, Cooper MR, Cohen R, Burtness B, Bos M, D'Andrea G, Seidman A, Norton L, Gunnett K, Falcey J, Anderson V, Waksal H, Mendelsohn J. Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. J Clin Oncol. 2000 Feb;18(4):904-14. — View Citation
Bleeker MC, Heideman DA, Snijders PJ, Horenblas S, Dillner J, Meijer CJ. Penile cancer: epidemiology, pathogenesis and prevention. World J Urol. 2009 Apr;27(2):141-50. doi: 10.1007/s00345-008-0302-z. Epub 2008 Jul 8. Review. — View Citation
Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78. — View Citation
Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010 Jan;11(1):21-8. doi: 10.1016/S1470-2045(09)70311-0. Epub 2009 Nov 10. Erratum in: Lancet Oncol. 2010 Jan;11(1):14. — View Citation
Calmon MF, Tasso Mota M, Vassallo J, Rahal P. Penile carcinoma: risk factors and molecular alterations. ScientificWorldJournal. 2011 Feb 3;11:269-82. doi: 10.1100/tsw.2011.24. Review. — View Citation
Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004 Jul 22;351(4):337-45. — View Citation
Curado M.P., Edwards B., Shin H.R. et al. Cancer Incidence in Five continents. Sci Publ. 2007. 160:570-573.
Di Lorenzo G, Buonerba C, Federico P, Perdonà S, Aieta M, Rescigno P, D'Aniello C, Puglia L, Petremolo A, Ferro M, Marinelli A, Palmieri G, Sonpavde G, Mirone V, De Placido S. Cisplatin and 5-fluorouracil in inoperable, stage IV squamous cell carcinoma of the penis. BJU Int. 2012 Dec;110(11 Pt B):E661-6. doi: 10.1111/j.1464-410X.2012.11453.x. Epub 2012 Sep 10. — View Citation
Dorff T. EGFR, TS and ERCC1 expression in penile squamous cancer. ASCO GU 2011. Not yet published.
Haas GP, Blumenstein BA, Gagliano RG, Russell CA, Rivkin SE, Culkin DJ, Wolf M, Crawford ED. Cisplatin, methotrexate and bleomycin for the treatment of carcinoma of the penis: a Southwest Oncology Group study. J Urol. 1999 Jun;161(6):1823-5. — View Citation
Lavens N, Gupta R, Wood LA. EGFR overexpression in squamous cell carcinoma of the penis. Curr Oncol. 2010 Feb;17(1):4-6. — View Citation
Pagliaro LC, Williams DL, Daliani D, Williams MB, Osai W, Kincaid M, Wen S, Thall PF, Pettaway CA. Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy for metastatic penile cancer: a phase II study. J Clin Oncol. 2010 Aug 20;28(24):3851-7. doi: 10.1200/JCO.2010.29.5477. Epub 2010 Jul 12. — View Citation
Philippou P, Shabbir M, Malone P, Nigam R, Muneer A, Ralph DJ, Minhas S. Conservative surgery for squamous cell carcinoma of the penis: resection margins and long-term oncological control. J Urol. 2012 Sep;188(3):803-8. doi: 10.1016/j.juro.2012.05.012. Epub 2012 Jul 19. — View Citation
Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O'Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U; FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009 May 2;373(9674):1525-31. doi: 10.1016/S0140-6736(09)60569-9. — View Citation
Rescigno P, Matano E, Raimondo L, Mainolfi C, Federico P, Buonerba C, Di Trolio R, D'Aniello C, Damiano V, Palmieri G, De Placido S, Di Lorenzo G. Combination of docetaxel and cetuximab for penile cancer: a case report and literature review. Anticancer Drugs. 2012 Jun;23(5):573-7. doi: 10.1097/CAD.0b013e328350ead7. — View Citation
Rigaud J, Avancès C, Camparo P, Culine S, Durand X, Iborra F, Mottet N, Sèbe P, Soulié M; Oncology Committee of the French Association of Urology (CCAFU). [Recommendations Onco-Urology 2010: Malignancies of the penis]. Prog Urol. 2010 Nov;20 Suppl 4:S279-89. doi: 10.1016/S1166-7087(10)70044-0. French. — View Citation
Smith Y, Hadway P, Biedrzycki O, Perry MJ, Corbishley C, Watkin NA. Reconstructive surgery for invasive squamous carcinoma of the glans penis. Eur Urol. 2007 Oct;52(4):1179-85. Epub 2007 Feb 20. — View Citation
Valverde C.M. BRAF and KRAS mutations in penile cancer and their correlation with clinical features. ASCO GU 2011. Not yet published.
Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009 Apr 2;360(14):1408-17. doi: 10.1056/NEJMoa0805019. — View Citation
Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. doi: 10.1056/NEJMoa0802656. — View Citation
Vermorken JB, Trigo J, Hitt R, Koralewski P, Diaz-Rubio E, Rolland F, Knecht R, Amellal N, Schueler A, Baselga J. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol. 2007 Jun 1;25(16):2171-7. — View Citation
* Note: There are 23 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Evaluation of the antitumor activity of Cetuximab treatment in terms of Objective Response Rate (ORR) at the end of treatment | Patients will be treated by TIP +/- Cetuximab for 1 cycle of 21 days. Subsequent treatment cycles will be performed only if patients meet correct biological analyses as defined by protocol, with a maximum of 5 more cycles of 21 days. Thus, the treatment duration will vary between patients from 3 weeks to 18 weeks. The treatment efficacy will be evaluated 28 days after the day 1 of the last cycle administered. Thus ORR will be evaluated between 4 weeks to 20 weeks after randomization, according to the amount of administered cycles. ORR is defined as the proportion of patients with best response consisting in a Complete Response (CR) or a Partial Response (PR) from the date of randomization to the date of the end of treatment visit (i.e 6 cycles of treatment as maximum) evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
4 weeks after the day 1 of the last cycle administered (i.e between 4 weeks to 20 weeks after randomization, according to the amount of administered cycles) | No |
Secondary | Evaluation of the Safety Profile of Cetuximab treatment | Safety profile is assessed throughout the study by incidence and intensity of Adverse Events displayed by patients using the CTCAE version 4.0 | From patient randomization up to the end of study i.e 28 months maximum after first patient inclusion | Yes |
Secondary | Evaluation of the antitumor activity of Cetuximab treatment in terms of Overall Survival (OS) at the end of the study | OS is defined as the time from the date of randomization to the date of death due to any cause. If a patient is not known to have died at the time of the analysis, OS will be censored at the date of last contact. | From patient randomization up to the end of study i.e 28 months maximum after first patient inclusion | No |
Secondary | Evaluation of the antitumor activity of Cetuximab treatment in terms of Progression-Free Survival (PFS) at the end of the study | PFS is defined as the time from the date of randomization to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event at the time of the analysis, PFS will be censored at the date of last adequate tumor assessment. | From patient randomization up to the end of study i.e 28 months maximum after first patient inclusion | No |
Secondary | Evaluation of Quality of Life during the Cetuximab treatment | Quality of life is assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30. It will be evaluated at Screening, at the beginning of cycle 4, and at the end of treatment i.e after 6 cycles maximum | From patient randomization up to the end of treatment (i.e between 4 weeks to 20 weeks after randomization, according to the amount of administered cycles) | No |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT02104063 -
Characterising Metastatic Penile Cancer Using Molecular Imaging - Hybrid MRI-PET [MRI-PET]
|
N/A | |
Not yet recruiting |
NCT06161532 -
Sacituzumab Govitecan With or Without Atezolizumab Immunotherapy in Rare Genitourinary Tumors (SMART) Such as Small Cell, Adenocarcinoma, and Squamous Cell Bladder/Urinary Tract Cancer, Renal Medullary Carcinoma and Penile Cancer
|
Phase 2 | |
Completed |
NCT03517488 -
A Study of XmAb®20717 in Subjects With Selected Advanced Solid Tumors
|
Phase 1 | |
Recruiting |
NCT03221400 -
PEN-866 in Patients With Advanced Solid Malignancies
|
Phase 1/Phase 2 | |
Recruiting |
NCT04996849 -
Contemporary Characteristics of Penile Cancer
|