Efficacy and Safety of Cetuximab in Metastatic Penile Carcinoma (PENILANE)

NCT02014831 | Withdrawn Phase 2 DMC

• 1 other identifier: PENILANE
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of Cetuximab in metastatic penile carcinoma

Conditions

Squamous Cell Carcinoma of the Penis

Keywords

Squamous Cell Carcinoma of the penis; Stage N3; Metastasis; TIP; Cetuximab; Objective Response Rate; Safety profile; Overall Survival; Progression Free Survival; Quality of Life

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (4)

• Evaluation of the Safety Profile of Cetuximab treatment

  From patient randomization up to the end of study i.e 28 months maximum after first patient inclusion

• Evaluation of the antitumor activity of Cetuximab treatment in terms of Overall Survival (OS) at the end of the study

  From patient randomization up to the end of study i.e 28 months maximum after first patient inclusion

• Evaluation of the antitumor activity of Cetuximab treatment in terms of Progression-Free Survival (PFS) at the end of the study

  From patient randomization up to the end of study i.e 28 months maximum after first patient inclusion

• Evaluation of Quality of Life during the Cetuximab treatment

  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)

Study Arms (2)

TIP

ACTIVE COMPARATOR

"Reference" arm; Patients will be treated with 6 cycles of Paclitaxel + Ifosfamide + Cisplatin (TIP treatment)

Drug: TIP

Cetuximab + TIP

EXPERIMENTAL

"Experimental" arm: Patients will be treated with 6 cycles of Paclitaxel + Ifosfamide + Cisplatin (TIP treatment) and weekly infusion of Cetuximab.

Drug: Cetuximab; Drug: TIP

Interventions

Cetuximab DRUG

Cetuximab treatment will be administered on specific days within a 21-days-cycle and for a maximum of 6 cycles as follow : CETUXIMAB I.V infusion of 400 mg/m2 on cycle 1 Day 0 for 2 hours, then 250 mg/m2 for subsequent infusions for 1 hour on Day 8, Day 15 and next cycles Day1, Day8, Day15. In case of documented toxicities, 2 drugs doses reductions are allowed according specific algorithms indicated in protocol

Cetuximab + TIP

TIP DRUG

The TIP combination of treatments will be administered on specific days within a 21-days-cycle and for a maximum of 6 cycles as follow : PACLITAXEL I.V infusion of 175 mg/m2, for 3 hours, on Day 1 of the cycle. IFOSFAMIDE I.V infusion of 1200 mg/m2, for 2 hours, on Day 1, Day 2, Day 3 of the cycle. CISPLATINE I.V infusion of 25 mg/m2, for 1 hour, on Day 1, Day 2, Day 3. In case of documented toxicities, 2 drugs doses reductions are allowed according specific algorithms indicated in protocol

Cetuximab + TIP; TIP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,

You may not qualify if:

• 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,

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (7)

CHRU Strasbourg

Strasbourg, Bas Rhin, 67098, France

Location

Institut Paoli Calmettes

Marseille, Bouches du Rhône, 13273, France

Location

Institut Bergonié

Bordeaux, Gironde, 33076, France

Location

Institut Claudius Regaud

Toulouse, Haute Garonne, 31052, France

Location

Centre Léon Bérard

Lyon, Rhône, 69373, France

Location

Institut Curie

Paris, Île-de-France Region, 75005, France

Location

APHP Hôpital Saint Louis

Paris, Île-de-France Region, 75475, France

Location

Related Publications (23)

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• Curado M.P., Edwards B., Shin H.R. et al. Cancer Incidence in Five continents. Sci Publ. 2007. 160:570-573.

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• 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.

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• Rigaud J., Avancès C., Camparo P. et al. Recommendations en onco-urologie 2010: Tumeurs malignes du penis. Progrès en oncologie. 2010. Suppl.4:279-289.

  BACKGROUND

• 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.

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• 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. doi: 10.1016/j.eururo.2007.02.038. Epub 2007 Feb 20.

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• Andersson P, Kolaric A, Windahl T, Kirrander P, Soderkvist 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.

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• Dorff T. EGFR, TS and ERCC1 expression in penile squamous cancer. ASCO GU 2011. Not yet published.

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MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Helen BOYLE, Doctor

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2013
• First Posted: December 18, 2013
• Study Start: February 1, 2016
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: February 25, 2016

Record last verified: 2016-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (7)