dMR During First Line Treatment of Non Squamous Lung Cancer: Time Course and Prognostic and Predictive Impact. (BevMar)
Primary Purpose
Non-small Cell Lung Cancer
Status
Unknown status
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
dMRT
Bevacizumab
paclitaxel and carboplatin
Sponsored by
About this trial
This is an interventional diagnostic trial for Non-small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
- Written informed consent obtained prior to any study-specific procedure
- Age ≥18 years
- Able to comply with the protocol
- Histologically or cytologically documented inoperable, metastatic (Stage IV) non small cell lung cancer
- ECOG PS status 0-1
- Life expectancy ≥12 weeks
Adequate haematological function:
- Normal values of absolute neutrophil and platelet count, and a hemoglobin value ≥9 g/dL
Adequate liver function:
- Total bilirubin <1.5 x ULN, AST, ALT <2.5 x ULN
Adequate renal function:
- Calculated creatinine clearance ≥50 mL/min, a urine dipstick for proteinuria <2+.
- Normal values of INR within 7 days prior to enrolment
- If female, should not be pregnant or breast-feeding. Women with an intact uterus (unless amenorrhoeic for the last 24 months) must have a negative serum pregnancy test within 28 days prior to enrolment into the study.
Exclusion Criteria:
- Mixed, non-small cell and small cell tumours or mixed adenosquamous carcinomas with a predominant squamous component
- Known EGFR mutation or ALK translocation
- History of haemoptysis
- Evidence of tumour invading major blood vessels on imaging. The investigator or the local radiologist must exclude evidence of tumour that is fully contiguous with, surrounding, or extending into the lumen of a major blood vessel (e.g. pulmonary artery or superior vena cava)
- Evidence of CNS metastases, even if previously treated. If suspected, the patient should be scanned within 28 days prior to enrolment to rule out CNS metastases
- Previous treatment with chemotherapy or other anticancer agent
- Previous radiotherapy of the primary tumour. Palliative extrathoracic radiotherapy is allowed prior to enrolment or during treatment
- Major surgery (including open biopsy), significant traumatic injury within 28 days prior to enrolment or anticipation of the need for major surgery during study treatment
- Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion
- Current or recent (within 10 days of first dose of bevacizumab) use of aspirin (> 325mg/day) or use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes.
- History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding
- Uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg)
- Clinically significant (i.e. active) cardiovascular disease
- Non-healing wound, active peptic ulcer or bone fracture
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment
- Women with an intact uterus (unless amenorrhoeic for the last 24 months) not using effective, means of contraception during the study and for a period of 6 months following the last administration of bevacizumab. Men who do not agree to use effective contraception during the study and for a period of 90 days following the last administration of bevacizumab. Men who do not agree to use effective contraception during the study and for a period of 90 days following the last administration of bevacizumab
- Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment
- Known hypersensitivity to bevacizumab or any of its excipients, and any of the chemotherapies
- Evidence of ongoing or active infection, any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications
- Patients diagnosed with a tracheo-oesophageal fistula
- History of thrombotic disorders within the last 6 months prior to enrolment.
- Contraindications for MRI: pacemaker and/or non-MRI compatible metallic implants/objects/devices/fragments.
Sites / Locations
- Dept of Lung and Allergy, Karolinska university hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
dMRT, Bevacizumab, Chemotherapy
Arm Description
dMRT: Magnetic Resonance Tomograph, Baseline, day 8, day 28, day 92, progression/relapse. Bevacizumab: 7.5mg/kg every 3 weeks for 3 cycles. Standard of care NSCLC first-line chemotherapy, doublets containing paclitaxel and carboplatin are preferred, every 3 weeks for 3 cycles. Thereafter Bevacizumab 7.5mg/kg every 3 weeks until progression/relapse or unacceptable toxicity.
Outcomes
Primary Outcome Measures
dMRT changes during treatment
Diffusion magnetic resonance tomography of lung lesions.
Secondary Outcome Measures
Response to treatment
CT of lungs, clinical examinations
3. Time to disease progression (defined as the time period from the start of first-line therapy to investigator assessed disease progression)
CT, clinical examinations
Duration of survival
Defined as the time period from the start of first-line therapy to death.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02195336
Brief Title
dMR During First Line Treatment of Non Squamous Lung Cancer: Time Course and Prognostic and Predictive Impact.
Acronym
BevMar
Official Title
Diffusion MR (dMRT) During First Line Treatment of Non Squamous Lung Cancer With Chemotherapy Combined With Bevacizumab: Time Course and Prognostic and Predictive Impact.
Study Type
Interventional
2. Study Status
Record Verification Date
July 2014
Overall Recruitment Status
Unknown status
Study Start Date
August 2014 (undefined)
Primary Completion Date
June 2016 (Anticipated)
Study Completion Date
June 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Karl Kölbeck
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
To date, there are no methods to reliably select which patients with non-squamous non-small cell lung cancer (NSCLC) that benefit most from treatment with bevacizumab. Data have shown that high levels of plasma VEGF are prognostic and correlates with a worse disease outcome in some tumour types, including advanced NSCLC.
Recent data are suggestive of a predictive value of imaging techniques for early detection of antiangiogenic treatment efficacy in different cancers. To our knowledge there are no presented data available on correlation between changes in diffusion-weighted MR and response to bevacizumab treatment in lung cancer. The current study is designed as a pilot study to prospectively investigate changes in MR variables during treatment with bevacizumab and to detect signals of prognostic and/or predictive value of MR changes during treatment.
Detailed Description
A Non Interventional, open-label, single arm, single institution pilot study. Eligible patients will be monitored by diffusion-weighted magnetic resonance tomography (dMRT) during treatment with bevacizumab + chemotherapy for up to four cycles followed by bevacizumab maintenance therapy until disease progression.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
dMRT, Bevacizumab, Chemotherapy
Arm Type
Experimental
Arm Description
dMRT: Magnetic Resonance Tomograph, Baseline, day 8, day 28, day 92, progression/relapse.
Bevacizumab: 7.5mg/kg every 3 weeks for 3 cycles. Standard of care NSCLC first-line chemotherapy, doublets containing paclitaxel and carboplatin are preferred, every 3 weeks for 3 cycles.
Thereafter Bevacizumab 7.5mg/kg every 3 weeks until progression/relapse or unacceptable toxicity.
Intervention Type
Device
Intervention Name(s)
dMRT
Other Intervention Name(s)
Magnetic Resonance Tomograph
Intervention Description
Baseline, day 8, day 28, day 92, progression/relapse.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
7.5mg/kg every 3 weeks for 3 cycles. Thereafter every 3 weeks until progression/relapse or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
paclitaxel and carboplatin
Intervention Description
Standard of care NSCLC first-line chemotherapy Every 3 weeks for 3 cycles. Doublets containing paclitaxel and carboplatin are preferred
Primary Outcome Measure Information:
Title
dMRT changes during treatment
Description
Diffusion magnetic resonance tomography of lung lesions.
Time Frame
Baseline, Day 8, Day 28, Day 92, At relapse.
Secondary Outcome Measure Information:
Title
Response to treatment
Description
CT of lungs, clinical examinations
Time Frame
Baseline, Day 92, at 5, 7, 9, 12, 15, 18, 24 mo during follow up
Title
3. Time to disease progression (defined as the time period from the start of first-line therapy to investigator assessed disease progression)
Description
CT, clinical examinations
Time Frame
Baseline, Day 92, at 5, 7, 9, 12, 15, 18, 24 mo during follow up
Title
Duration of survival
Description
Defined as the time period from the start of first-line therapy to death.
Time Frame
At 5, 7, 9, 12, 15, 18, 24, 36 and 48 mo during follow up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written informed consent obtained prior to any study-specific procedure
Age ≥18 years
Able to comply with the protocol
Histologically or cytologically documented inoperable, metastatic (Stage IV) non small cell lung cancer
ECOG PS status 0-1
Life expectancy ≥12 weeks
Adequate haematological function:
Normal values of absolute neutrophil and platelet count, and a hemoglobin value ≥9 g/dL
Adequate liver function:
Total bilirubin <1.5 x ULN, AST, ALT <2.5 x ULN
Adequate renal function:
Calculated creatinine clearance ≥50 mL/min, a urine dipstick for proteinuria <2+.
Normal values of INR within 7 days prior to enrolment
If female, should not be pregnant or breast-feeding. Women with an intact uterus (unless amenorrhoeic for the last 24 months) must have a negative serum pregnancy test within 28 days prior to enrolment into the study.
Exclusion Criteria:
Mixed, non-small cell and small cell tumours or mixed adenosquamous carcinomas with a predominant squamous component
Known EGFR mutation or ALK translocation
History of haemoptysis
Evidence of tumour invading major blood vessels on imaging. The investigator or the local radiologist must exclude evidence of tumour that is fully contiguous with, surrounding, or extending into the lumen of a major blood vessel (e.g. pulmonary artery or superior vena cava)
Evidence of CNS metastases, even if previously treated. If suspected, the patient should be scanned within 28 days prior to enrolment to rule out CNS metastases
Previous treatment with chemotherapy or other anticancer agent
Previous radiotherapy of the primary tumour. Palliative extrathoracic radiotherapy is allowed prior to enrolment or during treatment
Major surgery (including open biopsy), significant traumatic injury within 28 days prior to enrolment or anticipation of the need for major surgery during study treatment
Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion
Current or recent (within 10 days of first dose of bevacizumab) use of aspirin (> 325mg/day) or use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes.
History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding
Uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg)
Clinically significant (i.e. active) cardiovascular disease
Non-healing wound, active peptic ulcer or bone fracture
History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment
Women with an intact uterus (unless amenorrhoeic for the last 24 months) not using effective, means of contraception during the study and for a period of 6 months following the last administration of bevacizumab. Men who do not agree to use effective contraception during the study and for a period of 90 days following the last administration of bevacizumab. Men who do not agree to use effective contraception during the study and for a period of 90 days following the last administration of bevacizumab
Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment
Known hypersensitivity to bevacizumab or any of its excipients, and any of the chemotherapies
Evidence of ongoing or active infection, any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications
Patients diagnosed with a tracheo-oesophageal fistula
History of thrombotic disorders within the last 6 months prior to enrolment.
Contraindications for MRI: pacemaker and/or non-MRI compatible metallic implants/objects/devices/fragments.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Karl-Gustav Kölbeck, MD
Phone
+46-8-51774960
Email
karl.kolbeck@karolinska.se
First Name & Middle Initial & Last Name or Official Title & Degree
Eeva Alamartimo, RN
Phone
+46-8-51773918
Email
eeva.alamartimo@ki.se
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karl-Gustav Kölbeck, MD
Organizational Affiliation
Karolinska University Hospital, Dept of Lung and Allergy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dept of Lung and Allergy, Karolinska university hospital
City
Stockholm
Country
Sweden
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karl-Gustav Kölbeck, MD
Phone
+46-8-51774960
Email
karl.kolbeck@karolinska.se
First Name & Middle Initial & Last Name & Degree
Eeva Alamartimo, RN
Phone
+46-8-51773918
Email
eeva.alamartimo@ki.se
First Name & Middle Initial & Last Name & Degree
Mikael Skorpil, MED
12. IPD Sharing Statement
Learn more about this trial
dMR During First Line Treatment of Non Squamous Lung Cancer: Time Course and Prognostic and Predictive Impact.
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