Ovarian CancerPhase 1NCT00846612
Pharmacokinetic Study of Avastin and Doxil in Ovarian Cancer
A Phase 1 study testing Doxil and Bevacizumab (Avastin) in people with Ovarian Cancer, run by NYU Langone Health at 4 sites in United States.
Trial summary
This study is to study pharmacokinetics of Doxil using Doxil and Avastin on ovarian cancer patients who are resistant to or have relapsed from platinum-based therapy. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer
- What is being tested?
- Doxil and Bevacizumab (Avastin)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 4 sitesUnited States
- Study dates
- Jan 2008to Jun 2012
- Phase
- Phase 1
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must be platinum resistant
- No prior anthracycline use
- PS ≤ 2
- Lab values within certain limits (ANC > 1000, platelets > 100,000; ALT, AST 2x ULN, creatinine < 2.0);
- No more than 3 prior chemotherapy regimens, only 2 of which can have included platinum-containing regimens.
- Use of effective means of contraception in subjects of child-bearing potential
Who cannot join
- Disease-Specific Exclusions:
- Evidence of complete or partial bowel obstruction
- Need for IV hydration or TPN
- > 2 prior abdominal surgeries
- History of gastrointestinal perforation
- Gastrointestinal perforation due to any other cause within the last 6 months
Show all 29Show fewer
- General Medical Exclusions:
- Inability to comply with study and/or follow-up procedures
- Life expectancy of less than 12 weeks
- Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored Avastin cancer study
- Avastin-Specific Exclusions:
- Inadequately controlled hypertension (defined as systolic blood pressure greater than 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
- Any prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E of the protocol)
- History of myocardial infarction or unstable angina within 6 months prior to study enrollment
- History of stroke or transient ischemic attack within 6 months prior to study enrollment
- Known CNS disease
- Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
- Symptomatic peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
- History of abdominal fistula, or intra-abdominal abscess within 6 months prior to study enrollment
- Serious, non-healing wound, ulcer, or bone fracture
- Proteinuria at screening as demonstrated by either
- Urine protein:creatinine (UPC) ratio no less than 1.0 at screening OR
- Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
- Known hypersensitivity to any component of Avastin
- Pregnant (positive pregnancy test) or lactating. No effective means of contraception (men and women) in subjects of child-bearing potential
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Univ. of New Mexico cancer research and treatment center
Albuquerque, New Mexico, 87131
Bellevue Hospital
New York, New York, 10016
NYU Cancer Center
New York, New York, 10016
NYU medical center (Tisch Hospital)
New York, New York, 10016
About this study
Official title: Phase II and Pharmacokinetic Study of Avastin and Doxil in the Treatment of Platinum-resistant or Refractory Ovarian Cancer
This study is to study pharmacokinetics of Doxil using Doxil and Avastin on ovarian cancer patients who are resistant to or have relapsed from platinum-based therapy.
Read the detailed description
This study registration at clinicaltrials.gov is divided into 2 records. This record (NCT00846612) is for pharmacokinetics of Doxil. Another record (NCT00945139) describes the efficacy and safety of the combination treatment.
Treatment upon diagnosis of epithelial ovarian cancer (EOC) consists of surgery to achieve maximal tumor debulking followed by platinum-based chemotherapy (carboplatin + paclitaxel). Recently, optimally (e.g., < 1 cm residual disease) debulked patients appear to benefit from regimens that include intraperitoneal administration of cisplatin. While complete response (CR) is frequently achieved, by two years 50% of the patients show signs of recurrence.
When EOC presenting at an advanced stage recurs, even after a CR had been achieved, it can no longer be totally eradicated. Nevertheless, a number of drugs lead to objective responses, patients benefit with a prolongation of survival. Anti-tumor activity of Doxil against ovarian cancer was noted in a phase I study, and this was followed by a phase II study that demonstrated activity in platinum and paclitaxel refractory disease. In the expanded phase II experience at the University of Southern California, responses to Doxil occurred preferably in disease that was not bulky and after fewer prior treatments. Typically, several cycles were required for maximum response, and some patients had prolonged stable disease. Subsequently, the study of Gordon et al established the preferred role of this drug formulation in the 2nd line-setting. It is logical, therefore, to build on this agent in trying to improve the outcome of patients with recurrent ovarian cancer, and in particular, to consider a combination with Avastin, since Avastin has shown agent activity in retrospective data and recent studies in EOC.
A combination of Doxil with Avastin has several aspects of interest to ovarian cancer treatment: 1) independent single-agent activity, 2) enhanced localization of Doxil is possible via increased half-life (if liposomal egress is diminished) and decreased tumoral interstitial pressure, 3) improved Doxil distribution, and 4) likely favorable toxicity profile since Doxil's only common problematic toxicity is to the skin (palmar-plantar erythrodysesthesia or PPE). Pharmacokinetic issues will be addressed in selected patients, by comparing cycle 1 (without Avastin) with cycle 2 (with Avastin).
- Conditions
- Ovarian Cancer
- Being tested
- Doxil, Bevacizumab (Avastin)
- Keywords
- refractory, avastin, doxil, relapsed, ovarian cancer, platinum-resistant
- Medical subject headings
- Ovarian Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxilDrug
Also called pegylated doxorubicin liposome
1 cycle: 3 weeks; 30 mg/m^2, IV, every cycle
Bevacizumab (Avastin)Drug
Also called Avastin
1 cycle: every 3 weeks; 15 mg/kg, IV, beginning on cycle 2 and every cycle 20-24 hours following Doxil administration
| Study group | Role | What they receive |
|---|---|---|
| Avastin-Doxil | Experimental | Not described Receives: Drug: Doxil; Drug: Bevacizumab (Avastin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
change in peak plasma concentration of Doxil without and with Avastin
In cycle 1, patients were treated only with Doxil; in cycle 2, patients were treated with Doxil and Avastin.
Measured: 1 hour, 1, 4, 7, 10, 14, and 21 days post-dose in cycle 1 and cycle 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2009 (estimated)
- Study startJan 2008
- Primary completionSep 2010
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., University of New Mexico Cancer Center
- Responsible party
- Sponsor
- Investigators
- Franco Muggia, MD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00846612
- Sponsor's protocol ID
- 06-948
- Other IDs
- Genentech AVF3910s
- Status last verified
- Sep 2019
- First submitted
- 18 Feb 2009
- Last updated
- 30 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II and Pharmacokinetic Study of Avastin and Doxil in the Treatment of Platinum-resistant or Refractory Ovarian Cancer
- ClinicalTrials.gov ID
- NCT00846612
- Acronym / sponsor ID
- 06-948
- Conditions
- Ovarian Cancer
- Keywords
- refractory, avastin, doxil, relapsed, ovarian cancer, platinum-resistant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- Genentech, Inc., University of New Mexico Cancer Center
- Study start
- Jan 2008
- Primary completion
- Sep 2010 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 19 Feb 2009 (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.
This study is to study pharmacokinetics of Doxil using Doxil and Avastin on ovarian cancer patients who are resistant to or have relapsed from platinum-based therapy.
Detailed description
This study registration at clinicaltrials.gov is divided into 2 records. This record (NCT00846612) is for pharmacokinetics of Doxil. Another record (NCT00945139) describes the efficacy and safety of the combination treatment.
Treatment upon diagnosis of epithelial ovarian cancer (EOC) consists of surgery to achieve maximal tumor debulking followed by platinum-based chemotherapy (carboplatin + paclitaxel). Recently, optimally (e.g., < 1 cm residual disease) debulked patients appear to benefit from regimens that include intraperitoneal administration of cisplatin. While complete response (CR) is frequently achieved, by two years 50% of the patients show signs of recurrence.
When EOC presenting at an advanced stage recurs, even after a CR had been achieved, it can no longer be totally eradicated. Nevertheless, a number of drugs lead to objective responses, patients benefit with a prolongation of survival. Anti-tumor activity of Doxil against ovarian cancer was noted in a phase I study, and this was followed by a phase II study that demonstrated activity in platinum and paclitaxel refractory disease. In the expanded phase II experience at the University of Southern California, responses to Doxil occurred preferably in disease that was not bulky and after fewer prior treatments. Typically, several cycles were required for maximum response, and some patients had prolonged stable disease. Subsequently, the study of Gordon et al established the preferred role of this drug formulation in the 2nd line-setting. It is logical, therefore, to build on this agent in trying to improve the outcome of patients with recurrent ovarian cancer, and in particular, to consider a combination with Avastin, since Avastin has shown agent activity in retrospective data and recent studies in EOC.
A combination of Doxil with Avastin has several aspects of interest to ovarian cancer treatment: 1) independent single-agent activity, 2) enhanced localization of Doxil is possible via increased half-life (if liposomal egress is diminished) and decreased tumoral interstitial pressure, 3) improved Doxil distribution, and 4) likely favorable toxicity profile since Doxil's only common problematic toxicity is to the skin (palmar-plantar erythrodysesthesia or PPE). Pharmacokinetic issues will be addressed in selected patients, by comparing cycle 1 (without Avastin) with cycle 2 (with Avastin).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Avastin-Doxil | Experimental | Drug: Doxil, Drug: Bevacizumab (Avastin) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients must be platinum resistant
- No prior anthracycline use
- PS ≤ 2
- Lab values within certain limits (ANC > 1000, platelets > 100,000; ALT, AST 2x ULN, creatinine < 2.0);
- No more than 3 prior chemotherapy regimens, only 2 of which can have included platinum-containing regimens.
Key exclusion criteria (29 listed)
- Disease-Specific Exclusions:
- General Medical Exclusions:
- Avastin-Specific Exclusions:
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 |
|---|---|---|
| DoxilAlso: pegylated doxorubicin liposome1 cycle: 3 weeks; 30 mg/m^2, IV, every cycle | Drug | Avastin-Doxil |
| Bevacizumab (Avastin)Also: Avastin1 cycle: every 3 weeks; 15 mg/kg, IV, beginning on cycle 2 and every cycle 20-24 hours following Doxil administration | Drug | Avastin-Doxil |
Primary outcome
change in peak plasma concentration of Doxil without and with Avastin
Time frame: 1 hour, 1, 4, 7, 10, 14, and 21 days post-dose in cycle 1 and cycle 2
In cycle 1, patients were treated only with Doxil; in cycle 2, patients were treated with Doxil and Avastin.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2019.
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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.
Franco Muggia, MD principal investigator
NYU Langone Health
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Doxil and Bevacizumab (Avastin) in people with Ovarian Cancer, run by NYU Langone Health at 4 sites in United States.
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 6 inclusion and 29 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: finished, as of the sponsor's last update on 30 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
change in peak plasma concentration of Doxil without and with Avastin (time frame: 1 hour, 1, 4, 7, 10, 14, and 21 days post-dose in cycle 1 and cycle 2). 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 30 Sep 2019.