E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
localized or loco-regional esophageal cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10015362 |
E.1.2 | Term | Esophageal cancer |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this clinical study is to evaluate the efficacy of OncoGel based on overall tumor response at the primary tumor site. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this clinical study are to further evaluate the efficacy of OncoGel and to determine its safety in combination with chemoradiotherapy (CRT). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Disease criteria: Subject’s esophageal cancer must meet all of the following: a) Confirmation: Histologically or cytologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction. Biopsy or cytology of the primary tumor or of involved regional lymph nodes is acceptable. b) Stage: Tumors must be TNM stage T2-T3, N any, M0 (no evidence of disseminated cancer except regional nodes such as supraclavicular and celiac) as determined by endoscopic ultrasound. c) Disease extent: Disease must be limited to the esophagus or the gastroesophageal junction, including: i)Tumor does not extend more than 2 cm into the stomach ii)Tumor does not extend into proximal one-third of the esophagus (Note: Bronchoscopy is required if tumor is <26 cm from the incisors or at or above the carina) iii)No tracheal-esophageal fistulas present iv) No apparent direct invasion by the tumor into the mucosa of the trachea or major bronchus as determined by bronchoscopy or other method. v) No vascular invasion or involvement by the tumor d) No evidence of metastatic disease: disease must be localized to the esophagus, including i) no malignant cytology of the pleura, pericardium or peritoneum ii) no radiographic evidence of distant organ involvement including lung, liver, bone or brain (Note: any imaging study suspicious of liver metastases must be followed up with a negative biopsy prior to enrolling subject in the study) 2) Medically able to tolerate major abdominal and/or thoracic surgery 3) Able to undergo EUS procedure and pass EUS probe through esophageal lumen 4) Able to receive concurrent systemic chemotherapy (cisplatin and 5-FU) and RT 5) Clinical management plan includes esophagectomy after completion of two courses of CRT 6) Karnofsky Performance Status of ≥60 (refer to Section 13.2 for details) 7) Minimum life expectancy of 4 months as determined by the Investigator 8) Adequate hematologic function, defined as a) Absolute neutrophil count (ANC) ≥1500/mm3 b) Platelet count ≥100,000/mm3 c) Hemoglobin ≥9 g/dL 9) Adequate hepatic function, defined as a) Total bilirubin <1.5 X upper limit of normal (ULN) b) AST and ALT <3 X ULN c) Albumin ≥3.0 g/dL 10) Adequate renal function, defined as a) Serum creatinine <1.5 mg/dL and/or creatinine clearance ≥65 mL/min 11) ≥18 years old 12) If subject is female, she is of a) Non-childbearing potential (defined as surgically sterile or one year post-menopausal) b) Childbearing potential using adequate birth control and having a negative pregnancy test performed at Screening and again within 5 days of Dosing Day 1; adequate birth control measures are defined as hormonal, chemical or barrier methods or abstinence. Other birth control methods must receive Sponsor approval prior to subject enrollment 13) Capable of understanding and agreeing to fulfill the requirements of the protocol 14) Sign the IRB/EC approved consent form.
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E.4 | Principal exclusion criteria |
- History of anaphylaxis to planned CT contrast agent; subjects with history of minor, mild allergic reactions (eg, hives, rash, pruritis) to planned CT contrast agent may be premedicated with prednisone or other medications per institutional standard of care - Prior esophageal stent insertion, laser or photodynamic therapy - Prior chest RT or major esophageal surgery - Any prior receipt of cytotoxic chemotherapeutic agents - Prior receipt of other cancer treatments (ie, Chelation therapy), vaccines or biological response modifiers/growth factors (ie, GM-CSF, IL-2) within the past 4 weeks. Note: hormonal therapies (eg, tamoxifen, anastrozole) and topical agents (eg, 5-FU, imiquimod) will be allowed; no washout period will be required for these agents. - Prior malignancy unless disease free for ≥3 years Note: basal cell/squamous carcinoma of the skin, in situ cervical or breast carcinoma, or superficial transitional cell bladder carcinoma will be allowed - Significant currently active systemic diseases including uncontrolled diabetes, severe heart disease (New York Heart Association Class III or IV, see Section 13.4), uncontrolled hypertension, myocardial infarction within 3 months, severe bronchial obstruction, uncontrolled seizure disorder, or peripheral neuropathy greater than CTCAE grade 1 - Allergies to any of the active or inactive components of OncoGel (ie, allergies to degradable PLGA [poly(lactide-co-glycolide) sutures]) - Receipt of an investigational drug or device within 30 days prior to signing informed consent - Any medical condition or other circumstance that, in the Investigator’s opinion, would prevent completion of the study, interfere with analysis of the study results, or potentially aversely affect subject safety.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be overall tumor response at the primary tumor site based on measurement of primary tumor volume (excluding involved lymph nodes) by spiral CT. An independent panel will undertake a blinded review of the CT scans and will calculate tumor volume. The OR rate is defined as the proportion of subjects achieving a CR or PR. A CR is defined as disappearance of the target esophageal lesion based on the spiral CT scan at Week 12. A PR is defined, using modified RECIST criteria, as a ≥65% decrease in tumor volume from baseline to Week 12 using spiral CT.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
blinded assessment for primary efficacy endpoint |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Best Supportive Care: systemic chemotherapy and radiation therapy |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |