Malignant AscitesPhase 2NCT01262612
Cediranib as Palliative Treatment in Patients With Symptomatic Malignant Ascites or Pleural Effusion
A Phase 2 study testing immediate cediranib in people with Malignant Ascites and Malignant Pleural Effusion, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
In some patients with cancer there are also cancer cells in the abdominal cavity or between the lung membranes. These cancer cells create too much moisture in the abdominal cavity or between the lung membranes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Ascites, Malignant Pleural Effusion
- What is being tested?
- immediate cediranib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2010to Dec 2011
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Symptomatic malignant ascites and/or pleural effusion (from a histological proven solid malignancy which is refractory to standard anti-tumour therapy of for which no standard therapy exists)
- Karnofsky score ≥ 50 if the low performance score is due to ascites and/or pleural effusion, otherwise ≥ 60
- Age ≥ 18 years
- Written informed consent
Who cannot join
- Contraindications for treatment with cediranib:
- The presence of a pleural or peritoneal tap
- Untreated unstable brain or meningeal metastases.
- Previous treatment with chemotherapeutic agents or tyrosine kinase inhibitors (TKIs) within 14 days prior to the first dose of cediranib, with cetuximab within 30 days prior to the first dose of cediranib, or with bevacizumab within 60 days prior to the first dose of cediranib
- Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count ≤1.5 x 109/L or platelet count ≤100 x 109/L
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2,5 x ULN
Show all 22Show fewer
- Serum creatinine > 1.5 x ULRR or a creatinine clearance of ≤ 50mL/min calculated by Cockcroft-Gault
- Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart unless urinary protein < 1.5g in a 24 hr period
- Prothrombin time (PT) and activated partial thromboplastin time (APTT) > 2 x ULN History of significant gastrointestinal impairment, as judged by the Investigator, that would significantly affect the absorption of cediranib, including the ability to swallow the tablet whole. Patients with an ileostoma.
- Patients with a history of poorly controlled hypertension with resting blood pressure >150/100 in the presence or absence of a stable regimen of anti-hypertensive therapy. Patients who are currently receiving maximal doses of calcium channel blockers or more than 1 antihypertensive for the treatment of hypertension are also ineligible.
- Any evidence of severe or uncontrolled diseases e.g., unstable or uncompensated respiratory, cardiac, hepatic or renal disease.
- Unresolved toxicity > CTC grade 1 from previous anti-cancer therapy (including radiotherapy) except alopecia (if applicable) or polyneuropathy.
- Mean QTc with Bazetts correction >470msec in screening ECG or history of familial long QT syndrome
- Significant haemorrhage (>30mL bleeding/episode in previous 3 months) or haemoptysis (>5mL fresh blood in previous 4 weeks)
- Recent (<14 days) major surgery prior to entry into the study, or a surgical incision that is not fully healed
- Pregnant or breast-feeding women or women of childbearing potential with a positive pregnancy test prior to receiving study medication
- Known risk of the patient transmitting HIV, hepatitis B or C via infected blood
- Treatment with an investigational (non-registered) drug within 30 days prior to the first dose of cediranib
- Other concomitant anti-cancer therapy (including LHRH agonists) except steroids
- Concomitant use of any medication that may significantly affect hepatic cytochrome P450 drug metabolising activity by way of enzyme induction (e.g., phenytoin) or inhibition (e.g., ketoconazole, ritonavir, erythromycin) within 2 weeks if the first dose of cediranib and throughout the study period
- Patients being treated with anticoagulants (with the exception of low molecular weight heparin).
- Patients previously treated with anthracyclines (total of > 550 mg/m2 doxorubicine) and an ejection fraction on the MUGA scan below 40%
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 Phase II Study of Cediranib as Palliative Treatment in Patients With Symptomatic Malignant Ascites or Pleural Effusion
In some patients with cancer there are also cancer cells in the abdominal cavity or between the lung membranes. These cancer cells create too much moisture in the abdominal cavity or between the lung membranes. If there is fluid in the abdominal cavity (ascites fluid) this can bring on abdominal distension, abdominal pain, loss of appetite, fatigue, bloating and sometimes wheezing. Too much fluid between the lung membranes (we call this pleural fluid) gives breathlessness, chest pain and coughing. The use of diuretics may offer a small group of patients symptom reduction. Additionally, the fluid can be drained through a needle puncture or fluid collection (through a biopsy). But usually, the moisture quickly returns.
Previous research done in this hospital with cediranib showed that with some patients with cancer who suffered from fluid in the abdominal cavity or between the lung membranes, this moisture reduces while using this drug. It also reduced the symptoms caused by this excessive moisture.
The current study is conducted to see whether patients with cancer and fluid in the abdominal cavity or fluid between the lung blades benefit from using cediranib. This involves not only whether the amount moisture reduces, but also if the complains decrease. In addition, we will carefully consider the possible side effects of cediranib.
Read the detailed description
Malignant ascites is a difficult clinical problem. Increasing intra-abdominal pressure resulting from fluid accumulation may cause anorexia, sleep disturbance, pain, dyspnoea, abdominal distension, fatigue, nausea vomiting and reduced mobility. The main complaints of pleural effusion are dyspnoea and cough. Paracentesis and thoracentesis provide relief for a very limited period.
Studies have shown high concentrations of VEGF in malignant ascites and pleural effusion. Beneficial effects of treatment with an intravenous or intraperitoneal antibody against VEGF on malignant ascites have been reported. In the recent past we have treated two patients with symptomatic malignant ascites (colorectal cancer and ovarian cancer, respectively) in a phase I study with cediranib. Shortly after start of cediranib, within a couple of days, the ascites disappeared. However, after stopping cediranib for progressive disease on other sites the ascites reappeared within days. Therefore, one of those patients was treated with cediranib as palliative treatment until two days before his death, which was beneficial for this patient.
In this phase II study we would like to investigate the effects of treatment with cediranib as palliative treatment on malignant ascites or pleural effusion.
- Conditions
- Malignant Ascites, Malignant Pleural Effusion
- Being tested
- immediate cediranib, Start cediranib after 28 days Best Supportive Care
- Keywords
- cediranib, malignant ascites, malignant pleural effusion
- Medical subject headings
- Pleural Effusion, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
immediate cediranibDrug
Also called AZD2171
cediranib 30 mg on day one; Special in this study is the possibility to decrease (to a minimum of 15 mg) or increase the dose (to a maximum of 30 mg oid) during the study to get an individualized optimal palliative treatment with cediranib. The patient will continue cediranib as long as a clinical benefit is experienced, independent of tumour evaluation. Each dose changes should be documented with clear reasoning and documentation of the approach taken
Start cediranib after 28 days Best Supportive CareDrug
Also called AZD2171
patients in this group will start with cediranib after one month best supportive care. Special in this study is the possibility to decrease (to a minimum of 15 mg) or increase the dose (to a maximum of 30 mg oid) during the study to get an individualized optimal palliative treatment with cediranib. The patient will continue cediranib as long as a clinical benefit is experienced, independent of tumour evaluation. Each dose changes should be documented with clear reasoning and documentation of the approach taken.
| Study group | Role | What they receive |
|---|---|---|
| immediate treatment with cediranib | Active comparator | 8 patients with ascites and 8 patients with pleural effusion will start immediate treatment with cediranib Receives: Drug: immediate cediranib |
| start cediranib after 28 days BSC | Active comparator | patients in group B will start with cediranib after one month best supportive care. Receives: Drug: Start cediranib after 28 days Best Supportive Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
puncture free survival
If the puncture free survival after start of treatment with cediranib (time to first need for paracentesis or thoracentesis or time to death, which event occurred first) is more than 44 days the treatment of ascites and/or pleural effusion with cediranib is effective.
Measured: 44 days
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 startApr 2010
- Primary completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant AscitesStudies 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
- 12 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
- NCT01262612
- Sponsor's protocol ID
- UMCNONCO201001
- Status last verified
- Jul 2013
- First submitted
- 15 Dec 2010
- Last updated
- 15 Jul 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Cediranib as Palliative Treatment in Patients With Symptomatic Malignant Ascites or Pleural Effusion
- ClinicalTrials.gov ID
- NCT01262612
- Acronym / sponsor ID
- UMCNONCO201001
- Conditions
- Malignant Ascites, Malignant Pleural Effusion
- Keywords
- cediranib, malignant ascites, malignant pleural effusion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Apr 2010
- Primary completion
- Dec 2011 (actual)
- 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.
In some patients with cancer there are also cancer cells in the abdominal cavity or between the lung membranes. These cancer cells create too much moisture in the abdominal cavity or between the lung membranes. If there is fluid in the abdominal cavity (ascites fluid) this can bring on abdominal distension, abdominal pain, loss of appetite, fatigue, bloating and sometimes wheezing. Too much fluid between the lung membranes (we call this pleural fluid) gives breathlessness, chest pain and coughing. The use of diuretics may offer a small group of patients symptom reduction. Additionally, the fluid can be drained through a needle puncture or fluid collection (through a biopsy). But usually, the moisture quickly returns.
Previous research done in this hospital with cediranib showed that with some patients with cancer who suffered from fluid in the abdominal cavity or between the lung membranes, this moisture reduces while using this drug. It also reduced the symptoms caused by this excessive moisture.
The current study is conducted to see whether patients with cancer and fluid in the abdominal cavity or fluid between the lung blades benefit from using cediranib. This involves not only whether the amount moisture reduces, but also if the complains decrease. In addition, we will carefully consider the possible side effects of cediranib.
Detailed description
Malignant ascites is a difficult clinical problem. Increasing intra-abdominal pressure resulting from fluid accumulation may cause anorexia, sleep disturbance, pain, dyspnoea, abdominal distension, fatigue, nausea vomiting and reduced mobility. The main complaints of pleural effusion are dyspnoea and cough. Paracentesis and thoracentesis provide relief for a very limited period.
Studies have shown high concentrations of VEGF in malignant ascites and pleural effusion. Beneficial effects of treatment with an intravenous or intraperitoneal antibody against VEGF on malignant ascites have been reported. In the recent past we have treated two patients with symptomatic malignant ascites (colorectal cancer and ovarian cancer, respectively) in a phase I study with cediranib. Shortly after start of cediranib, within a couple of days, the ascites disappeared. However, after stopping cediranib for progressive disease on other sites the ascites reappeared within days. Therefore, one of those patients was treated with cediranib as palliative treatment until two days before his death, which was beneficial for this patient.
In this phase II study we would like to investigate the effects of treatment with cediranib as palliative treatment on malignant ascites or pleural effusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| immediate treatment with cediranib | Active comparator | Drug: immediate cediranib8 patients with ascites and 8 patients with pleural effusion will start immediate treatment with cediranib |
| start cediranib after 28 days BSC | Active comparator | Drug: Start cediranib after 28 days Best Supportive Carepatients in group B will start with cediranib after one month best supportive care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Symptomatic malignant ascites and/or pleural effusion (from a histological proven solid malignancy which is refractory to standard anti-tumour therapy of for which no standard therapy exists)
- Karnofsky score ≥ 50 if the low performance score is due to ascites and/or pleural effusion, otherwise ≥ 60
- Age ≥ 18 years
- Written informed consent
Key exclusion criteria (22 listed)
- The presence of a pleural or peritoneal tap
- Untreated unstable brain or meningeal metastases.
- Previous treatment with chemotherapeutic agents or tyrosine kinase inhibitors (TKIs) within 14 days prior to the first dose of cediranib, with cetuximab within 30 days prior to the first dose of cediranib, or with bevacizumab within 60 days prior to the first dose of cediranib
- Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count ≤1.5 x 109/L or platelet count ≤100 x 109/L
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2,5 x ULN
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 |
|---|---|---|
| immediate cediranibAlso: AZD2171cediranib 30 mg on day one; Special in this study is the possibility to decrease (to a minimum of 15 mg) or increase the dose (to a maximum of 30 mg oid) during the study to get an individualized optimal palliative treatment with cediranib. The patient will continue cediranib as long as a clinical benefit is experienced, independent of tumour evaluation. Each dose changes should be documented with clear reasoning and documentation of the approach taken | Drug | immediate treatment with cediranib |
| Start cediranib after 28 days Best Supportive CareAlso: AZD2171patients in this group will start with cediranib after one month best supportive care. Special in this study is the possibility to decrease (to a minimum of 15 mg) or increase the dose (to a maximum of 30 mg oid) during the study to get an individualized optimal palliative treatment with cediranib. The patient will continue cediranib as long as a clinical benefit is experienced, independent of tumour evaluation. Each dose changes should be documented with clear reasoning and documentation of the approach taken. | Drug | start cediranib after 28 days BSC |
Primary outcome
puncture free survival
Time frame: 44 days
If the puncture free survival after start of treatment with cediranib (time to first need for paracentesis or thoracentesis or time to death, which event occurred first) is more than 44 days the treatment of ascites and/or pleural effusion with cediranib is effective.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2013.
Related trials for Malignant Ascites
RecruitingPhase 1/2
Lenvatinib in Combination With Nivolumab Plus Chemotherapy in Metastatic Gastric Cancer Patients With Malignant Ascites
STOMACH NEOPLASM, Gastric Cancer
Active, not recruiting
Retlirafusp Alfa Plus SOX and Intraperitoneal Nab-Paclitaxel for Advanced Gastric/GEJ Cancer With Malignant Ascites
Gastric Cancer (GC), Peritoneal Metastases From Gastric Cancer
RecruitingObservational study
Anti-PD-1 in Combination With Systemic Chemotherapy With Nab-paclitaxel Intraperitoneal Infusion for Untreated Advanced Gastric Cancer With Malignant Ascites
Gastric Cancer Peritoneal Metastases, Gastric Cancer (GC)
RecruitingPhase 1
TLR9 Immunotherapy for Peritoneal Carcinomatosis
Malignant Ascites, Colorectal Adenocarcinoma
Not yet recruitingEarly Phase 1
NK521 in the Treatment of Advanced Solid Tumors
Hepatocellular Carcinoma (HCC), Ovarian Cancer
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 immediate cediranib in people with Malignant Ascites and Malignant Pleural Effusion, 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 4 inclusion and 22 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 15 Jul 2013. 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. 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?
puncture free survival (time frame: 44 days). 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 15 Jul 2013.