AzTrials
AzTrials

Ovarian CancerPhase 1/2NCT01035658

Pazopanib/Doxil in Adv Relapsed Plat Sensitive or Resistant Ovarian, Fallopian or Primary Peritoneal Adenocarcinoma

A Phase 1/2 study testing Pazopanib and Doxil in people with Ovarian Cancer and Fallopian Tube Cancer, run by SCRI Development Innovations, LLC at 4 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

In this study, patients with relapsed or refractory ovarian cancer will receive treatment with pazopanib and liposomal doxorubicin (Doxil) until disease progression or unacceptable toxicity occurs. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Pazopanib and Doxil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
4 sitesUnited States
Study dates
Jan 2010to Mar 2014
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histologically or cytologically confirmed diagnosis of epithelial ovarian carcinoma (FIGO Stage II to IV), primary peritoneal cancer or fallopian tube.
  • One or 2 previous chemotherapy regimens for advanced ovarian cancer. At least one of these regimens must have contained a platinum agent.
  • Patients who are platinum-resistant (relapse <6 months after completing a platinum-containing regimen) or platinum sensitive (relapse ≥ 6 months after platinum-containing regimen) are eligible.
  • Radiographically documented progression per RECIST criteria (version 1.1) or progression of CA-125 during or subsequent to the last chemotherapy regimen.
  • Measurable disease (RECIST criteria) or evaluable disease with elevated CA-125 level. Patients with normal CT scans and elevated CA-125 levels as the only indication of disease are not eligible. ECOG performance status of 0 or 1.
  • Normal left ventricular ejection fraction (LVEF) according to institutional standards.
Show all 22Show fewer
  • Adequate recovery from recent surgery. At least 1 week must have elapsed from the time of a minor surgery (with the exception of portacath placement); at least 4 weeks must have elapsed from the time of a major surgery.
  • Laboratory values as follows:
  • Absolute neutrophil count (ANC) ≥1500/μL
  • Hemoglobin (Hgb) ≥9g/dL. Patients may not have received RBC transfusions within 7 days of screening assessment.
  • Platelets ≥100,000/L
  • AST or ALT must be <2.5 x ULN (concomitant elevations in bilirubin and AST/ALT >1.0 x ULN are not permitted).
  • Total bilirubin <1.5 x the institutional ULN (if Gilberts syndrome, direct bilirubin ≤1.5 x ULN)
  • International normalized ratio (INR) 1.2 and activated partial thromboplastin time (aPTT) 1.2 the ULN (except for patients receiving anti-coagulation therapy)
  • Cr ≤ 1.5 x ULN. If Cr >1.5 x ULN, then calculated creatinine clearance must be ≥50 mL/min
  • Urine protein creatinine (UPC) ratio ≤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).
  • Patients must be 18 years of age.
  • Life expectancy of ≥12 weeks.
  • Patient must be accessible for treatment and follow-up.
  • Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.
  • Females of non-childbearing potential (i.e., physiologically incapable of becoming pregnant), include a female who has had: a hysterectomy, a bilateral oophorectomy, a bilateral tubal ligation, or is post-menopausal. Patients not using hormone replacement therapy (HRT) must have experienced total cessation of menses for ≥1 year and be ≥45 years old, or in questionable cases, have a follicle stimulating hormone (FSH) value >40 mIU/mL and an estradiol value <40pg/mL. Patients using HRT must have experienced total cessation of menses for ≥1 year and be ≥45 years old, or have had documented evidence of menopause based on FSH and estradiol prior to the initiation of HRT.
  • Women of childbearing potential must have a negative serum or urine pregnancy test performed ≤14 days prior to start of treatment. Women of childbearing potential must use effective birth control measures during treatment. Acceptable contraceptive methods include: 1) an intrauterine device with a documented failure rate of ≤1% per year, 2) a vasectomized partner who is sterile prior to the patient"s entry and is the sole sexual partner for that female, 3) abstinence 14 days prior to study entry, throughout the dosing period, and for at least 21 days after the last dose of protocol therapy, 4) double-barrier contraception, or 5) oral contraception. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.

Who cannot join

  • Patients may not have received either investigational or marketed agents, which act by primary anti-angiogenic mechanisms (i.e. bevacizumab).
  • Prior treatment with liposomal doxorubicin.
  • Patients with brain metastases. (Baseline imaging required only if clinically indicated).
  • Patients with known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.
  • Patients with hemoptysis within 6 weeks of first dose of study drug.
  • Patients who are pregnant or breast feeding.
Show all 23Show fewer
  • Impaired cardiac function including any of the following conditions within the past 6 months:
  • NYHA Class II, III or IV heart failure.
  • QTc prolongation or other significant ECG abnormalities.
  • Myocardial infarction or unstable angina
  • Coronary artery bypass graft surgery
  • Symptomatic peripheral vascular disease
  • History of sustained ventricular tachycardia.
  • Patients must not have taken any potent CYP3A4 inhibitors <= 14 days prior to enrollment including but not limited to:
  • ketoconazole, itraconazole, troleandomycin, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, amprenavir, nefazodone, fluvoxamine, diltiazem, verapamil, mibefradil, cimetidine, cyclosporine, and grapefruit juice.
  • Uncontrolled hypertension (systolic blood pressure [BP] >180 or diastolic BP >100mm Hg) or uncontrolled cardiac arrhythmias (Patients with hypertension controlled by antihypertensive therapies are eligible.)
  • History of cerebrovascular accident (CVA), MI within 12 months or venous thrombosis within 12 weeks. (Patients with previous history of venous thrombosis on a stable dose of anticoagulation are allowed.)
  • Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit safety and compliance with study requirements.
  • Inability to swallow whole tablets.
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g., active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or significant small bowel resection).
  • Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
  • Use of any non-approved or investigational agent <= 30 days prior to administration of the first dose of study drug. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
  • Past or current history of neoplasm other than the entry diagnosis with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix, or other cancers cured by local therapy alone and a DFS >= 5 years.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Oncology Hematology Care

    Cincinnati, Ohio, 45242

  • Florida Cancer Specialists

    Fort Myers, Florida, 33901

  • Tennessee Oncology, PLLC

    Nashville, Tennessee, 37023

  • Florida Hospital Cancer Insitute

    Orlando, Florida, 32804

Other trials in United States

About this study

Official title: A Phase I/II Study of the Combination of Pazopanib and Liposomal Doxorubicin (Doxil) in Patients With Advanced Relapsed Platinum-Sensitive or Platinum-Resistant Ovarian, Fallopian Tube or Primary Peritoneal Adenocarcinoma

In this study, patients with relapsed or refractory ovarian cancer will receive treatment with pazopanib and liposomal doxorubicin (Doxil) until disease progression or unacceptable toxicity occurs. The Phase I portion will define the dose limiting toxicity (DLT) of pazopanib and liposomal doxorubicin when administered in combination. Once the maximum tolerated dose has been identified in the Phase I portion, the Phase II portion will evaluate efficacy and safety of this combination in the same patient population.

Read the detailed description

In this study, patients with relapsed or refractory ovarian cancer will receive treatment with pazopanib and liposomal doxorubicin (Doxil) until disease progression or unacceptable toxicity occurs. The Phase I portion will define the dose limiting toxicity (DLT) of pazopanib and liposomal doxorubicin when administered in combination. Once the maximum tolerated dose has been identified in the Phase I portion, the Phase II portion will evaluate efficacy and safety of this combination in the same patient population.

Being tested
Pazopanib, Doxil
Keywords
Pazopanib, Doxil, Liposomal doxorubicin, Advanced relapsed, platinum-sensitive, platinum-resistant
Medical subject headings
Ovarian Neoplasms, Fallopian Tube Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PazopanibDrug

    Also called Systemic therapy

    All patients will begin treatment with a 7-day run in period of single-agent pazopanib. Patients will receive pazopanib orally days 1-28 of a 28 day cycle.

  • DoxilDrug

    Also called Systemic therapy, Liposomal doxorubicin

    Liposomal doxorubicin (Doxil) will be administered IV on day 1 of a 28-day treatment cycle

Study groups in NCT01035658
Study groupRoleWhat they receive
Dose Level 1ExperimentalSystemic therapy with pazopanib and liposomal doxorubicin (Doxil). Single-agent pazopanib will be given for a 7 day run-in period, followed by a combination of pazopanib (400mg) and liposomal doxorubicin (40mg) administered in 28-day treatment cycles. Cycles will continue until disease progression, unacceptable toxicity or withdrawal.
Receives: Drug: Pazopanib; Drug: Doxil
Dose Level -1ExperimentalSystemic therapy with pazopanib and liposomal doxorubicin (Doxil). Single-agent pazopanib will be given for a 7 day run-in period, followed by a combination of pazopanib (400mg) and liposomal doxorubicin (30mg) administered in 28-day treatment cycles. Cycles will continue until disease progression, unacceptable toxicity or withdrawal.
Receives: Drug: Pazopanib; Drug: Doxil
Dose Level 1 SequentialExperimentalSystemic therapy with pazopanib and liposomal doxorubicin (Doxil). In this schedule, liposomal doxorubicin (30mg) was given on day 1, and pazopanib (400mg) was given days 3 - 26 of each 28 day cycle. Cycles will continue until disease progression, unacceptable toxicity or withdrawal.
Receives: Drug: Pazopanib; Drug: Doxil
Dose Level 2 SequentialExperimentalSystemic therapy with pazopanib and liposomal doxorubicin (Doxil). In this schedule, liposomal doxorubicin (40mg) was given on day 1, and pazopanib (400mg) was given days 3 - 26 of each 28 day cycle. Cycles will continue until disease progression, unacceptable toxicity or withdrawal.
Receives: Drug: Pazopanib; Drug: Doxil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I: Maximum Tolerated Dose (MTD) of Pazopanib and Liposomal Doxorubicin

    The MTD of the drug combination will be determined as the highest dose at which ≤1 of 6 subjects experiences a Grade 3 or Grade 4 DLT according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.

    Measured: 18 months

  2. Phase I - Dose Limiting Toxicities

    As requested, this outcome measure reports the number of patients experiencing dose limiting toxicities (DLTs) in the Phase I portion of the study

    Measured: 18 months

  3. Phase II: Progression Free Survival

    Defined as from date of randomization until objective tumor progression or death. Response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) and CA-125 response in patients using the Rustin Criteria.

    Measured: 18 months

Secondary outcomes (3)

  1. Phase II - Overall Survival of Patients With Relapsed/Refractory Ovarian Cancer Following Treatment With Pazopanib and Liposomal Doxorubicin

    Measured: 18 months

  2. Response Rate in the Subsets of Patients With Platinum-sensitive and Platinum-refractory Ovarian Carcinoma

    The response rate in the subsets of patients with platinum-sensitive and platinum-refractory ovarian carcinoma is evaluated as a measure of efficacy of pazopanib/liposomal doxorubicin. Response rate ( Percentage of patients whose disease decreased (Partial response - PR) and/or disappears (Complete response - CR) after treatment) was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) and CA-125 response in patients using the Rustin Criteria. CR: disappearance of all target and nontarget lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Normalization of CA125, if elevated at baseline, is required for ovarian carcinoma studies. PR is >= 30% decrease in the sum of longest diameter(LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of nontarget lesions and no new lesions.

    Measured: 18 months

  3. Number of Participants Experiencing Adverse Events With the Combination of Pazopanib and Liposomal Doxorubicin Doses

    An adverse event (AE) is the development of an undesirable medical condition, or the deterioration of a pre-existing medical condition (other than the condition that is being treated by the trial) following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. The number of participants experiencing such adverse events that are possibly/probably/definitely related to the study drugs are reported here.

    Measured: 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Dec 2009 (estimated)
  2. Study startJan 2010
  3. Primary completionJun 2012
  4. Study completionMar 2014

Why it stopped: Based on analyses in Phase I, the study did not advance to Phase II.

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01035658
Sponsor's protocol ID
SCRI GYN 26
Status last verified
Oct 2021
First submitted
17 Dec 2009
Last updated
28 Oct 2021
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pazopanib and Doxil in people with Ovarian Cancer and Fallopian Tube Cancer, run by SCRI Development Innovations, LLC 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 22 inclusion and 23 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 28 Oct 2021. 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 combined 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.

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?

Yes. Results are posted in the registry (first posted 21 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Phase I: Maximum Tolerated Dose (MTD) of Pazopanib and Liposomal Doxorubicin (time frame: 18 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01035658.

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 28 Oct 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in