Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT02580058
Previous Study | Return to List | Next Study

A Study Of Avelumab Alone Or In Combination With Pegylated Liposomal Doxorubicin Versus Pegylated Liposomal Doxorubicin Alone In Patients With Platinum Resistant/Refractory Ovarian Cancer (JAVELIN Ovarian 200)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02580058
Recruitment Status : Active, not recruiting
First Posted : October 20, 2015
Last Update Posted : June 11, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE October 16, 2015
First Posted Date  ICMJE October 20, 2015
Last Update Posted Date June 11, 2019
Actual Study Start Date  ICMJE December 21, 2015
Actual Primary Completion Date September 19, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 21, 2017)
  • Overall Survival (OS) [ Time Frame: randomization up to approximately 20 months ]
    Overall survival was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.
  • Progression Free Survival (PFS) [ Time Frame: randomization up to approximately 20 months ]
    To demonstrate that avelumab given alone or in combination with PLD is superior to PLD alone in prolonging Progression Free Survival (PFS) in patients with platinum resistant/platinum refractory ovarian cancer.
Original Primary Outcome Measures  ICMJE
 (submitted: October 16, 2015)
Overall Survival (OS) [ Time Frame: randomization up to approximately 20 months ]
Overall survival was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.
Change History Complete list of historical versions of study NCT02580058 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2015)
  • OR (Objective Response) [ Time Frame: Baseline up to approximately 20 months ]
    Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the longest diameters dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions.
  • PFS (Progression Free Survival) [ Time Frame: randomization up to approximately 20 months ]
    The period from study entry until disease progression, death or date of last contact.
  • DR (Duration of Response) [ Time Frame: first documentation of objective tumor response up to approximately 20 months ]
    Duration of response (DR) is defined, for patients with an objective response per RECIST v1.1, as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.
  • DC (Disease Control) [ Time Frame: Randomization up to approximately 20 months ]
    Defined as complete response (CR), partial response (PR), or stable disease (SD) 24 weeks according to the RECIST version 1.1 recorded from randomization until disease progression or death due to any cause. The DC rate (DCR) on each randomized treatment arm will be estimated by dividing the number of patients with CR, PR, or SD 24 weeks by the number of patients randomized to the treatment arm. The corresponding exact 2 sided 95% CI for the DC rates will be provided by treatment arm
  • Ctrough for avelumab [ Time Frame: pre dose and at the end of infusion (immediately before the end of avelumab infusion) on Days 1 and 15. ]
    Ctrough is defined as the trough plasma concentrate at the end of an avelumab interval
  • Cmax for avelumab [ Time Frame: pre dose and at the end of infusion (immediately before the end of avelumab infusion) on Days 1 and 15. ]
    Cmax defined as the maximum plasma concentration of avelumab
  • Cmax for PLD [ Time Frame: in the first 12 patients pre dose, immediately prior to end of infusion, and at 2, 6, 24, and 336 hours (Day 15) post start infusion of PLD on Day 1 of next dose. ]
    Cmax defined as the maximum plasma concentration of PLD
  • Vd (volume of distribution) for PLD [ Time Frame: in the first 12 patients pre dose, immediately prior to end of infusion, and at 2, 6, 24, and 336 hours (Day 15) post start infusion of PLD on Day 1 of next dose. ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug
  • CL (clearance) for PLD [ Time Frame: in the first 12 patients pre dose, immediately prior to end of infusion, and at 2, 6, 24, and 336 hours (Day 15) post start infusion of PLD on Day 1 of next dose. ]
    CL is a quantitative measure of the rate at which PLD is removed from the body
  • AUC (area under the concentration time curve) for PLD [ Time Frame: in the first 12 patients pre dose, immediately prior to end of infusion, and at 2, 6, 24, and 336 hours (Day 15) post start infusion of PLD on Day 1 of next dose. ]
    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption
  • Incidence of Anti-Drug Antibody (ADA) [ Time Frame: prior to start of avelumab infusion on Day 1 and at end of treatment for up to 24 months. ]
    immunogenicity assessment for avelumab
  • EORTC QLQ C30 [ Time Frame: once a month before dosing, up to 24 months ]
    European Organization for Research and Treatment of Cancer Quality of Life Questionnaire: 30 question survey and includes 5 functional domain subscales, including a physical functioning sub scale, a role functioning subscale, an emotional functioning sub scale, a cognitive functioning sub scale and a social functioning subscale. Higher scores on the functioning domains are indicative of higher levels of functioning
  • EORTC QLQ OV28 [ Time Frame: once a month before dosing, up to 24 months ]
    European Organization for Research and Treatment of Cancer Quality of Life Questionnaire: 28 item instrument with seven (7) functional domain subscales. The 7 subscales include: (i) an abdominal/gastrointestinal symptom subscale (7 items); (ii) a peripheral neuropathy subscale (3 items); (iii) an other chemotherapy side effects subscale (7 items); (iv) a hormonal/menopausal symptoms subscale (2 items); (v) a body image subscale (2 items); (vi) an attitude to disease and treatment subscale (3 items) and (vii) a sexual function subscale (4 items)
  • FOSI [ Time Frame: once a month before dosing, up to 24 months ]
    a very brief ovarian cancer symptom index derived from the FACT O (ie, Functional Assessment of Cancer Therapy Ovarian) to measure symptom response to treatment for ovarian cancer. The 8 item FOSI includes items assessing worry about future deterioration, contentment with QoL, and lack of energy in addition to 5 questions to assess GI related symptoms
  • EuroQoL EQ 5D [ Time Frame: once a month before dosing, up to 24 months ]
    Euro Quality of Life: 6 item patient completed questionnaire designed to assess health status in terms of a single index value or utility score. There are 2 components to the EuroQol EQ 5D: a Health State Profile which has individuals rate their level of problems (no, some or moderate, extreme) in 5 areas (mobility, self care, usual activities, pain/discomfort, and anxiety/depression) and a Visual Analogue Scale (VAS) in which patients rate their overall health status from 0 (worst imaginable) to 100 (best imaginable). Published weights are available that allow for the creation of a single summary score. Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction
  • Tumor Tissue Biomarkers [ Time Frame: Baseline, optional sample at disease progression ]
    May include but not limited to PD L1 expression and tumor infiltrating CD8+ T lymphocytes by IHC, and/or tissue expression of FoxP3, PD 1, PD L2
  • Nab (neutralizing antibodies) against avelumab [ Time Frame: performed if ADA is positive: prior to start of avelumab infusion on Day 1 and at end of treatment for up to 24 months. ]
    immunogenicity assessment for avelumab
Original Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2015)
  • OR (Objective Response) [ Time Frame: Baseline up to approximately 20 months ]
    Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the longest diameters dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions.
  • PFS (Progression Free Survival) [ Time Frame: randomization up to approximately 20 months ]
    The period from study entry until disease progression, death or date of last contact.
  • DR (Duration of Response) [ Time Frame: first documentation of objective tumor response up to approximately 20 months ]
    Duration of response (DR) is defined, for patients with an objective response per RECIST v1.1, as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.
  • DC (Disease Control) [ Time Frame: Randomization up to approximately 20 months ]
    Defined as complete response (CR), partial response (PR), or stable disease (SD) 24 weeks according to the RECIST version 1.1 recorded from randomization until disease progression or death due to any cause. The DC rate (DCR) on each randomized treatment arm will be estimated by dividing the number of patients with CR, PR, or SD 24 weeks by the number of patients randomized to the treatment arm. The corresponding exact 2 sided 95% CI for the DC rates will be provided by treatment arm
  • Ctrough for avelumab [ Time Frame: pre dose and at the end of infusion (immediately before the end of avelumab infusion) on Days 1 and 15. ]
    Ctrough is defined as the trough plasma concentrate at the end of an avelumab interval
  • Cmax for avelumab [ Time Frame: pre dose and at the end of infusion (immediately before the end of avelumab infusion) on Days 1 and 15. ]
    Cmax defined as the maximum plasma concentration of avelumab
  • Cmax for PLD [ Time Frame: in the first 12 patients pre dose, immediately prior to end of infusion, and at 2, 6, 24, and 336 hours (Day 15) post start infusion of PLD on Day 1 of next dose. ]
    Cmax defined as the maximum plasma concentration of PLD
  • Vd (volume of distribution) for PLD [ Time Frame: in the first 12 patients pre dose, immediately prior to end of infusion, and at 2, 6, 24, and 336 hours (Day 15) post start infusion of PLD on Day 1 of next dose. ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug
  • CL (clearance) for PLD [ Time Frame: in the first 12 patients pre dose, immediately prior to end of infusion, and at 2, 6, 24, and 336 hours (Day 15) post start infusion of PLD on Day 1 of next dose. ]
    CL is a quantitative measure of the rate at which PLD is removed from the body
  • AUC (area under the concentration time curve) for PLD [ Time Frame: in the first 12 patients pre dose, immediately prior to end of infusion, and at 2, 6, 24, and 336 hours (Day 15) post start infusion of PLD on Day 1 of next dose. ]
    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption
  • Incidence of Anti-Drug Antibody (ADA) [ Time Frame: prior to start of avelumab infusion on Day 1 and at end of treatment for up to 24 months. ]
    immunogenicity assessment for avelumab
  • EORTC QLQ C30 [ Time Frame: once a month before dosing, up to 24 months ]
    30 question survey and includes 5 functional domain subscales, including a physical functioning sub scale, a role functioning subscale, an emotional functioning sub scale, a cognitive functioning sub scale and a social functioning subscale. Higher scores on the functioning domains are indicative of higher levels of functioning
  • 7.2.2. EORTC QLQ OV28 [ Time Frame: once a month before dosing, up to 24 months ]
    28 item instrument with seven (7) functional domain subscales. The 7 subscales include: (i) an abdominal/gastrointestinal symptom subscale (7 items); (ii) a peripheral neuropathy subscale (3 items); (iii) an other chemotherapy side effects subscale (7 items); (iv) a hormonal/menopausal symptoms subscale (2 items); (v) a body image subscale (2 items); (vi) an attitude to disease and treatment subscale (3 items) and (vii) a sexual function subscale (4 items)
  • FOSI [ Time Frame: once a month before dosing, up to 24 months ]
    a very brief ovarian cancer symptom index derived from the FACT O (ie, Functional Assessment of Cancer Therapy Ovarian) to measure symptom response to treatment for ovarian cancer. The 8 item FOSI includes items assessing worry about future deterioration, contentment with QoL, and lack of energy in addition to 5 questions to assess GI related symptoms
  • EuroQoL EQ 5D [ Time Frame: once a month before dosing, up to 24 months ]
    6 item patient completed questionnaire designed to assess health status in terms of a single index value or utility score. There are 2 components to the EuroQol EQ 5D: a Health State Profile which has individuals rate their level of problems (no, some or moderate, extreme) in 5 areas (mobility, self care, usual activities, pain/discomfort, and anxiety/depression) and a Visual Analogue Scale (VAS) in which patients rate their overall health status from 0 (worst imaginable) to 100 (best imaginable). Published weights are available that allow for the creation of a single summary score. Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction
  • Tumor Tissue Biomarkers [ Time Frame: Baseline, optional sample at disease progression ]
    May include but not limited to PD L1 expression and tumor infiltrating CD8+ T lymphocytes by IHC, and/or tissue expression of FoxP3, PD 1, PD L2
  • Nab (neutralizing antibodies) against avelumab [ Time Frame: performed if ADA is positive: prior to start of avelumab infusion on Day 1 and at end of treatment for up to 24 months. ]
    immunogenicity assessment for avelumab
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Of Avelumab Alone Or In Combination With Pegylated Liposomal Doxorubicin Versus Pegylated Liposomal Doxorubicin Alone In Patients With Platinum Resistant/Refractory Ovarian Cancer (JAVELIN Ovarian 200)
Official Title  ICMJE A PHASE 3, MULTICENTER, RANDOMIZED, OPEN-LABEL STUDY OF AVELUMAB (MSB0010718C) ALONE OR IN COMBINATION WITH PEGYLATED LIPOSOMAL DOXORUBICIN VERSUS PEGYLATED LIPOSOMAL DOXORUBICIN ALONE IN PATIENTS WITH PLATINUM-RESISTANT/REFRACTORY OVARIAN CANCER
Brief Summary A Phase 3 global study comparing avelumab alone to avelumab plus PLD and to PLD alone to demonstrate that avelumab given alone or in combination with PLD is superior to PLD alone in prolonging Overall Survival in patients with platinum resistant/platinum refractory ovarian cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ovarian Cancer
Intervention  ICMJE
  • Biological: avelumab
    10 mg/kg will be given as a 1 hour intravenous infusion (IV) every 2 weeks (Q2W) in 4 week cycles
  • Drug: PLD
    PLD (Arm B, Arm C) 40 mg/m2 will be given as a 1 hour IV infusion every 4 weeks (Q4W) in 4 week cycles
    Other Name: doxorubicin, caelyx
Study Arms  ICMJE
  • Experimental: avelumab
    Arm A: avelumab alone
    Intervention: Biological: avelumab
  • Experimental: avelumab plus pegylated liposomal doxorubicin (PLD)
    Arm B: avelumab plus PLD
    Interventions:
    • Biological: avelumab
    • Drug: PLD
  • Active Comparator: PLD
    Arm C: PLD alone
    Intervention: Drug: PLD
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 3, 2018)
566
Original Estimated Enrollment  ICMJE
 (submitted: October 16, 2015)
550
Estimated Study Completion Date  ICMJE December 18, 2019
Actual Primary Completion Date September 19, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed epithelial ovarian, fallopian tube, or peritoneal cancer, including malignant mixed Müllerian tumors with high grade serous component.
  • Platinum resistant/refractory disease, defined as disease progression within 180 days following the last administered dose of platinum therapy (resistant), or lack of response or disease progression while receiving the most recent platinum based therapy (refractory), respectively.
  • Received up to 3 lines of systemic anticancer therapy for platinum sensitive disease, most recently platinum containing, and no prior systemic therapy for platinum resistant disease
  • Measurable disease by investigator assessment with at least 1 unidimensional measurable lesion by RECIST v.1.1 that has not previously been irradiated
  • Active autoimmune disease that might deteriorate when receiving an immunostimulatory agents. Patients with diabetes type I, vitiligo, psoriasis, hypo or hyperthyroid disease not requiring immunosuppressive treatment are eligible.

Mandatory tumor biopsy must be performed prior to enrollment for all patients (unless there is a documented clinical contraindication). In addition, availability of archived FFPE tumor tissue should be confirmed. If a patient underwent tumor tissue collection within 3 months prior to enrollment with no intervening treatment, and the sample is provided, then a new de novo tumor biopsy is not required.

Exclusion Criteria:

  • Non epithelial tumor or ovarian tumors with low malignant potential (ie, borderline tumors).
  • Prior therapy with an anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody (including ipilimumab, tremelimumab or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways).
  • Known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks prior to study entry and are neurologically stable.
  • Diagnosis of any other malignancy within 5 years prior to registration, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix.
  • Severe gastrointestinal conditions such as clinical or radiological evidence of bowel obstruction within 4 weeks prior to study entry, uncontrolled diarrhea in the last 4 weeks prior to enrollment, or history of inflammatory bowel disease.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   Czechia,   Denmark,   France,   Greece,   Hong Kong,   Hungary,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Norway,   Poland,   Russian Federation,   Singapore,   Spain,   Switzerland,   Taiwan,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02580058
Other Study ID Numbers  ICMJE B9991009
2015-003091-77 ( EudraCT Number )
JAVELIN OVARIAN 200 ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP