Irresectable Squamous Cell or Adenocarcinoma of the OesophagusPhase 2PANORAMICNCT01262183
Radio-chemotherapy With or Without Panitumumab (Vectibix®) in Irresectable Squamous Cell Carcinoma or Adenocarcinoma of the Oesophagus
A Phase 2 study testing CRT + Panitumumab and Concurrent chemoradiation therapy without panitumumab in people with Irresectable Squamous Cell or Adenocarcinoma of the Oesophagus, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
For esophageal cancer that can not be removed by surgery, the choice of treatment is a combination of chemotherapy and radiotherapy. We call this combination- (or concurrent) chemoradiotherapy. Chemotherapy is treatment with drugs that kill cancer cells. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Irresectable Squamous Cell or Adenocarcinoma of the Oesophagus
- What is being tested?
- CRT + Panitumumab and Concurrent chemoradiation therapy without panitumumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteNetherlands
- Study dates
- Jan 2011to Oct 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 - 70years
- Histology proven SCC or adenocarcinoma of the oesophagus
- No proven (distant) metastases (ultrasonography, CT or MRI)
- No prior treatment for carcinoma of the oesophagus
- Karnofsky performance status ≥70% (appendix A)
- Irresectable disease as assessed by the multidisciplinary tumour board
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- All patients (male and female) must use effective contraception methods according to CPMP/ICH/286/95 if of reproductive potential (e.g. implants, injectables, combined oral contraceptives, IUDs, sexual abstinence or vasectomised partner), for the whole duration of the study and until six months after they received the last treatment dose
- No contraindications for cytotoxic therapy or panitumumab:
- No known hypersensitivity/allergy to any of the compounds used
- Haematology: Neutrophil count ≥ 1.5∙109 /L Thrombocyte count ≥ 100∙109 /L Haemoglobin ≥ 6.2 mmol/L (100 g/L)
- No known HIV infection or other condition of persistent immunodeficiency
- Renal function:
- Creatinine clearance (MDRD) ≥ 60 mL/min
- Hepatic function:
- Total bilirubin ≤ 1.5∙ULN
- AST, ALT, AP ≤ 2.5∙ULN
- Electrolyte balance:
- (albumin corrected) calcium ≤ 2.87 mmol/L (=11.5 mg/dl) but ≥ lower limit of normal (LLN)
- Magnesium ≥ LLN
- History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.
- No known other serious illness or medical condition present at entry in the study including: Unstable cardiac disease despite treatment, congestive heart failure NYHA grade 3 and 4 Clinically significantly abnormal electrocardiogram (ECG) or left ventricular ejection fraction (LVEF) below the institutional ULN
- Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrolment/randomisation
- Significant neurologic or psychiatric disorders
- Active uncontrolled infection Active disseminated intravasal coagulation
- Symptomatic peripheral neuropathy (CTCAE v3.0 term "neuropathy: sensory") ≥ grade 2 Ototoxicity (CTCAE v3.0 any term in "auditory/ear") ≥ grade 2 except if due to trauma or mechanical impairment due to tumour mass
- Other serious underlying medical condition which could impair the ability of the patient to participate in the study No or insufficient oral nutrient intake
- No prior exposure to EGFR pathway targeting agents
- No known drug abuse
- Absence of any psychological, familial, sociological (e.g. severe alcohol addiction expected to hamper protocol compliance) or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
- No participation in another interventional clinical trial in the preceding 30 days
- Written informed consent to participate to study must be given according to ICH/GCP, and national/local regulations.
Who cannot join
- Prior treatment for this tumour
- Prior treatment with radiation therapy in the area of the oesophagus or other site that will interfere with proposed treatment
- Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
- Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment.
- History of other prior malignancy in past 5 years, other than basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ.
- For the PET-scan the following exclusion criteria are used:
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- Severe claustrophobia
- Diabetes mellitus (type I and II)
- Serum glucose level >11 mmol/L
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
University Medical Centre Nijmegen
Nijmegen, Gelderland, 6500 HB
About this study
Official title: A Randomised Phase II Study of Radio-chemotherapy With or Without Panitumumab (Vectibix®) in Irresectable Squamous Cell Carcinoma or Adenocarcinoma of the Oesophagus
For esophageal cancer that can not be removed by surgery, the choice of treatment is a combination of chemotherapy and radiotherapy. We call this combination- (or concurrent) chemoradiotherapy. Chemotherapy is treatment with drugs that kill cancer cells. Both chemotherapy and radiotherapy make the tumour smaller and enhance each other's effect. The goal of treatment with chemotherapy and radiation therapy is to cure the cancer. Unfortunately only a small proportion of patients are cured with this treatment.
Improvements in the outcome of treatment may be expected by using the so-called "targeted" treatments. With esophageal cancer, a protein (the epidermal growth factor receptor (this is a kind of trap), the EGFR), is present in many tumours. This protein causes the tumor to grow. Panitumumab is a drug that blocks the functioning of this receptor (catcher), so that possibly the growth and spread of esophageal cancer is prevented.
Read more
The main objective of this trial is to see if survival of patients with inoperable esophageal cancer improves as panitumumab is added to standard treatment with chemoradiotherapy.
It will also investigate whether patients tolerate the addition of panitumumab to the standard treatment. Also, the biological characteristics of the tumor will be examined. In a proportion of patients it will be determined how the enhancement of the cancer is visible on an FDG-PET scan before the start of treatment and how this changes during the treatment. It will be also be evaluated how this treatment affects the survival.
Read the detailed description
A complete response rate of approximately 30% is achieved for standard treatment of irresectable carcinoma of the oesophagus, consisting of concurrent chemoradiation therapy (50.5 Gy + cisplatin/5-FU). Attempts to improve outcome by intensifying conventional cytotoxic drugs or increasing the radiation dose have not been successful. Future improvements will likely require the incorporation of targeted agents that probably will not add significant toxicity, the use of molecular predictors of response and early identification of responders. In both squamous cell carcinoma and adenocarcinoma of the oesophagus expression of EGFR is correlated with poor outcome. Furthermore the addition of cetuximab, a chimaeric EGFR antibody, to radiation therapy in head and neck cancer and non-small cell lung cancer showed a gain in overall survival. In head and neck cancer studies with the addition of panitumumab to chemo-radiation therapy are currently ongoing. Therefore, we propose to perform a randomised phase II study of chemo-radiation therapy with or without the combination of panitumumab (human EGFR antibody) in irresectable squamous cell carcinoma or adenocarcinoma of the oesophagus without distant metastases.
- Being tested
- CRT + Panitumumab, Concurrent chemoradiation therapy without panitumumab
- Keywords
- oesophagus cancer, chemoradiotherapy, panitumumab, irresectable
- Medical subject headings
- Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CRT + PanitumumabDrug
Day -7, day +15 and day +36: panitumumab 9.0 mg/kg i.v. Day +1 to +39: radiation therapy 1.8 Gy fractions 5 times per week to a cumulative dose of 50.4 Gy Day +1 and +29: cisplatin 75 mg/m2 i.v. Day +1 to +4 and +29 to +32: 5-fluorouracil 1000 mg/m2 i.v.
Concurrent chemoradiation therapy without panitumumabDrug
Day +1 to +39: radiation therapy 1.8 Gy fractions 5 times per week to a cumulative dose of 50.4 Gy Day +1 and +29: cisplatin 75 mg/m2 i.v. Day +1 to +4 and +29 to +32: 5-fluorouracil 1000 mg/m2 i.v.
| Study group | Role | What they receive |
|---|---|---|
| Concurrent chemoradiation therapy with panitumumab | Experimental | Not described Receives: Drug: CRT + Panitumumab |
| Concurrent chemoradiation therapy without panitumumab | Active comparator | Not described Receives: Drug: Concurrent chemoradiation therapy without panitumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
1-year overall survival
To describe the 1-year OS rate after concurrent CRT with or without panitumumab in irresectable carcinoma of the oesophagus. The control arm is used to validate whether the historical cohort used for comparison is similar to our success-rate.
Measured: 1-year
Secondary outcomes (6)
toxicity
Investigation of the acute and long-term toxicity of both study arms (according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0);
Measured: during treatment and follow up
PFS
PFS: interval between randomisation date and the date at which disease progression is established being not suspicious for a second cancer (histologically confirmed when in doubt) or date of death from any cause but clearly not related to disease- or treatment (e.g. accident). Patients still disease-free after 18 months follow-up or lost to follow-up or death clearly not related to disease or treatment (e.g. accident)), are censored at the date of the most recent follow-up or at the analysis cut-off date, whichever comes first.
Measured: between randomisation and date of PD
Response Rate
Response rate: partial (PR) or complete response (CR) according to RECIST 1.1 at 3 months after treatment
Measured: 3 months after treatment
pharmacodynamics of panitumumab
pharmacodynamics (PD) of panitumumab (EGFR, K-RAS, B-RAF, downstream signalling pathways ) compared between the biopsy at baseline (standard) and the biopsy one week after start chemo-radiation therapy
Measured: biopsy at baseline (standard) and the biopsy one week after start chemo-radiation therapy
Quantification of baseline FDG uptake (SUV) with PET, and SUV changes
baseline, 7 days after the first panitumumab dose or for start chemo-radiation therapy. during treatment with chemoradiation therapy after three weeks.
2-4 weeks after finishing treatment. 10-12 weeks after finishing treatment
Measured: baseline 7 days after the first panitumumab dose or for start chemo-radiation therapy. during treatment with chemoradiation therapy after three weeks.
CTCs and CECs
Measured: baseline,after 2 weeks during chemo-radiation therapy and 12 weeks after finishing treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2010 (estimated)
- Study startJan 2011
- Primary completionApr 2012
- Study completionOct 2012 (estimated)
Why it stopped: low recruitment numbers
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Irresectable Squamous Cell or Adenocarcinoma of the OesophagusStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- C.M.L. van Herpen, Md PhD, Principal investigator, University Medical Centre Nijmegen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01262183
- Sponsor's protocol ID
- UMCNONCO200905
- Acronym
- PANORAMIC
- Status last verified
- Apr 2012
- First submitted
- 15 Dec 2010
- Last updated
- 11 May 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Phase II Study of Radio-chemotherapy With or Without Panitumumab (Vectibix®) in Irresectable Squamous Cell Carcinoma or Adenocarcinoma of the Oesophagus
- ClinicalTrials.gov ID
- NCT01262183
- Acronym / sponsor ID
- PANORAMIC / UMCNONCO200905
- Keywords
- oesophagus cancer, chemoradiotherapy, panitumumab, irresectable
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low recruitment numbers
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- Apr 2012 (actual)
- Study completion
- Oct 2012 (estimated)
- First posted
- 17 Dec 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
For esophageal cancer that can not be removed by surgery, the choice of treatment is a combination of chemotherapy and radiotherapy. We call this combination- (or concurrent) chemoradiotherapy. Chemotherapy is treatment with drugs that kill cancer cells. Both chemotherapy and radiotherapy make the tumour smaller and enhance each other's effect. The goal of treatment with chemotherapy and radiation therapy is to cure the cancer. Unfortunately only a small proportion of patients are cured with this treatment.
Improvements in the outcome of treatment may be expected by using the so-called "targeted" treatments. With esophageal cancer, a protein (the epidermal growth factor receptor (this is a kind of trap), the EGFR), is present in many tumours. This protein causes the tumor to grow. Panitumumab is a drug that blocks the functioning of this receptor (catcher), so that possibly the growth and spread of esophageal cancer is prevented.
The main objective of this trial is to see if survival of patients with inoperable esophageal cancer improves as panitumumab is added to standard treatment with chemoradiotherapy.
It will also investigate whether patients tolerate the addition of panitumumab to the standard treatment. Also, the biological characteristics of the tumor will be examined. In a proportion of patients it will be determined how the enhancement of the cancer is visible on an FDG-PET scan before the start of treatment and how this changes during the treatment. It will be also be evaluated how this treatment affects the survival.
Detailed description
A complete response rate of approximately 30% is achieved for standard treatment of irresectable carcinoma of the oesophagus, consisting of concurrent chemoradiation therapy (50.5 Gy + cisplatin/5-FU). Attempts to improve outcome by intensifying conventional cytotoxic drugs or increasing the radiation dose have not been successful. Future improvements will likely require the incorporation of targeted agents that probably will not add significant toxicity, the use of molecular predictors of response and early identification of responders. In both squamous cell carcinoma and adenocarcinoma of the oesophagus expression of EGFR is correlated with poor outcome. Furthermore the addition of cetuximab, a chimaeric EGFR antibody, to radiation therapy in head and neck cancer and non-small cell lung cancer showed a gain in overall survival. In head and neck cancer studies with the addition of panitumumab to chemo-radiation therapy are currently ongoing. Therefore, we propose to perform a randomised phase II study of chemo-radiation therapy with or without the combination of panitumumab (human EGFR antibody) in irresectable squamous cell carcinoma or adenocarcinoma of the oesophagus without distant metastases.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Concurrent chemoradiation therapy with panitumumab | Experimental | Drug: CRT + Panitumumab |
| Concurrent chemoradiation therapy without panitumumab | Active comparator | Drug: Concurrent chemoradiation therapy without panitumumab |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Age 18 - 70years
- Histology proven SCC or adenocarcinoma of the oesophagus
- No proven (distant) metastases (ultrasonography, CT or MRI)
- No prior treatment for carcinoma of the oesophagus
- Karnofsky performance status ≥70% (appendix A)
Key exclusion criteria (9 listed)
- Prior treatment for this tumour
- Prior treatment with radiation therapy in the area of the oesophagus or other site that will interfere with proposed treatment
- Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
- Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment.
- History of other prior malignancy in past 5 years, other than basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CRT + PanitumumabDay -7, day +15 and day +36: panitumumab 9.0 mg/kg i.v. Day +1 to +39: radiation therapy 1.8 Gy fractions 5 times per week to a cumulative dose of 50.4 Gy Day +1 and +29: cisplatin 75 mg/m2 i.v. Day +1 to +4 and +29 to +32: 5-fluorouracil 1000 mg/m2 i.v. | Drug | Concurrent chemoradiation therapy with panitumumab |
| Concurrent chemoradiation therapy without panitumumabDay +1 to +39: radiation therapy 1.8 Gy fractions 5 times per week to a cumulative dose of 50.4 Gy Day +1 and +29: cisplatin 75 mg/m2 i.v. Day +1 to +4 and +29 to +32: 5-fluorouracil 1000 mg/m2 i.v. | Drug | Concurrent chemoradiation therapy without panitumumab |
Primary outcome
1-year overall survival
Time frame: 1-year
To describe the 1-year OS rate after concurrent CRT with or without panitumumab in irresectable carcinoma of the oesophagus. The control arm is used to validate whether the historical cohort used for comparison is similar to our success-rate.
6 secondary outcomes
toxicity
Time frame: during treatment and follow up
PFS
Time frame: between randomisation and date of PD
Response Rate
Time frame: 3 months after treatment
pharmacodynamics of panitumumab
Time frame: biopsy at baseline (standard) and the biopsy one week after start chemo-radiation therapy
Quantification of baseline FDG uptake (SUV) with PET, and SUV changes
Time frame: baseline 7 days after the first panitumumab dose or for start chemo-radiation therapy. during treatment with chemoradiation therapy after three weeks.
CTCs and CECs
Time frame: baseline,after 2 weeks during chemo-radiation therapy and 12 weeks after finishing treatment
Results and safety
The study was stopped early (reason given: low recruitment numbers). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2012.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
C.M.L. van Herpen, Md PhD principal investigator
University Medical Centre Nijmegen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CRT + Panitumumab and Concurrent chemoradiation therapy without panitumumab in people with Irresectable Squamous Cell or Adenocarcinoma of the Oesophagus, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 31 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: low recruitment numbers). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1-year overall survival (time frame: 1-year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2012.