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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
Results First Posted : November 19, 2019
Last Update Posted : November 19, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Biological: avelumab Drug: PLD Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 566 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 21, 2015
Actual Primary Completion Date : September 19, 2018
Estimated Study Completion Date : December 18, 2019


Arm Intervention/treatment
Experimental: avelumab
Arm A: avelumab alone
Biological: avelumab
10 mg/kg will be given as a 1 hour intravenous infusion (IV) every 2 weeks (Q2W) in 4 week cycles

Experimental: avelumab plus pegylated liposomal doxorubicin (PLD)
Arm B: avelumab plus PLD
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

Active Comparator: PLD
Arm C: PLD alone
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




Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: From randomization until the date of first documented progression or date of deaths from any cause, whichever came first, assessed up to 30 months (based on cutoff date: 19 September 2018). ]
    OS is defined as the time from the date of randomization to the date of death due to any cause. OS time was summarized by treatment arm using the Kaplan-Meier method.

  2. Progression Free Survival (PFS) Based on Blinded Independent Central Review (BICR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: From randomization to date of first documentation of PD or death due to any cause whichever was first (up to 30 months); based on cutoff date: 19 September 2018. ]
    PFS is defined as the time from date of randomization to the date of the first documentation of progression of disease (PD) or death due to any cause, whichever occurs first. PFS time was summarized by treatment arm using the Kaplan-Meier method. PFS based on BICR assessment was evaluated for this endpoint.


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) Based on BICR Assessment [ Time Frame: Tumor assessments as assessed by BICR were conducted at every 8 weeks from screening until documented disease progression (approximately up to 30 months); based on cutoff date: 19 September 2018. ]
    Percentage of participants achieved objective response (OR) based on BICR assessment is presented for this endpoint. OR is defined as a complete response (CR, disappearance of all target lesions) or partial response (PR, >=30% decrease under the baseline of the sum of diameters of all target measurable lesions) according to the RECIST (version 1.1) recorded from randomization until disease progression or death due to any cause. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met and before the first documentation of disease progression. Only tumor assessments performed on or before the start date of any further anti-cancer therapies are considered in the assessment of best overall response.

  2. ORR Based on Investigator Assessment [ Time Frame: Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018. ]
    Percentage of participants achieved OR based on investigator assessment is presented for this endpoint. OR is defined as a CR (disappearance of all target lesions) or PR (>=30% decrease under the baseline of the sum of diameters of all target measurable lesions) according to the RECIST (version 1.1) recorded from randomization until disease progression or death due to any cause. The ORR on each randomized treatment arm were estimated by dividing the number of participants with OR (CR or PR) by number of participants randomized to the respective treatment arm.

  3. PFS Based on Investigator Assessment According to RECIST Version 1.1 [ Time Frame: From randomization to date of first documentation of PD or death due to any cause whichever was first (up to 30 months); based on cutoff date: 19 September 2018. ]
    PFS is defined as the time from date of randomization to the date of the first documentation of PD or death due to any cause, whichever occurs first. PFS time was summarized by treatment arm using the Kaplan-Meier method.

  4. Duration of Response (DR) Based on BICR Assessment [ Time Frame: Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018. ]
    DR is defined, for participants with an OR per RECIST version 1.1, as the time from the first documentation of objective tumor response (CR [disappearance of all target lesions] or PR [>=30% decrease under the baseline of the sum of diameters of all target measurable lesions]) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.

  5. DR Based on Investigator Assessment [ Time Frame: Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018. ]
    DR is defined, for participants with an OR per RECIST version 1.1, as the time from the first documentation of objective tumor response (CR [disappearance of all target lesions] or PR [>=30% decrease under the baseline of the sum of diameters of all target measurable lesions]) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.

  6. Disease Control (DC) Rate Based on BICR Assessment [ Time Frame: Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018. ]
    Percentage of participants achieving DC based on BICR assessment is presented in this endpoint. DC is a best overall response of CR (disappearance of all target lesions), PR (>=30% decrease under the baseline of the sum of diameters of all target measurable lesions), non-complete response/non-progressive disease or stable disease (SD) according to the RECIST version 1.1.

  7. DC Rate Based on Investigator Assessment [ Time Frame: Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018. ]
    Percentage of participants achieving DC based on investigator assessment is presented in this endpoint. DC is a best overall response of CR (disappearance of all target lesions), PR (>=30% decrease under the baseline of the sum of diameters of all target measurable lesions), non-complete response/non-progressive disease or SD according to the RECIST version 1.1.

  8. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: From Cycle 1 Day 1 to 90 days after the last dose of study treatment (up to 2.7 years by primary completion date of 19 September 2018). ]
    An adverse event (AE) is any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; progression of the malignancy under study. Treatment emergent AEs are those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event is during the on-treatment period.

  9. Number of Participants With Laboratory Abnormalities [ Time Frame: From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018. ]
    The number of participants with following laboratory abnormalities meeting any of the Grades 1 to 4 classified according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) toxicity grading version 4.03 were summarized: hematology (anemia, lymphocyte count decreased, neutrophil count decreased; and platelet count decreased) and chemistry laboratory tests (creatinine increased; serum amylase increased and lipase increased).

  10. Change From Baseline in Vital Signs - Blood Pressure [ Time Frame: From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018. ]
    Vital signs included blood pressure and pulse rate. Changes from baseline in sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP) were summarized.

  11. Change From Baseline in Vital Signs - Pulse Rate [ Time Frame: From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018. ]
    Vital signs included blood pressure and pulse rate. Changes from baseline in sitting pulse rate were summarized.

  12. Number of Participants With Electrocardiogram (ECG) Abnormalities [ Time Frame: From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018. ]
    Categorical summarization ECG criteria were as follows: 1) QT interval, QTcB, QTcF and QTcP: increase from baseline >30 ms or 60 ms; absolute value > 450 ms, >480 ms and > 500 ms; 2) heart rate (HR): change from baseline >=20 bpm and absolute value <=50 bpm or >=120 bpm; 3) PR interval: absolute value >=220 ms and increase from baseline >=20 ms; 4) QRS: >= 120 ms.

  13. Number of Participants With % Left Ventricular Ejection Fraction (LVEF) Decrease From Baseline [ Time Frame: Screening, Cycle 3 Day 1 (repeated every 2 cycles) to the end of treatment/withdrawal visit, based on cutoff date: 19 September 2018. ]
    LVEF decrease was summarized by multiple-gated acquisition (MUGA)/ echocardiogram (ECHO) parameter. Participants with a LVEF% >=10 points and >= 15 points decrease from baseline during the on-treatment period were summarized.

  14. Number of Participants With PD-L1 Expression for PFS (Based on BICR Assessment) and for OS [ Time Frame: Biomarkers are measured only at screening. ]
    PD-L1 expression was assessed by immunohistochemistry. Participants were considered positive for PD-L1 if their baseline tissue sample demonstrated PD-L1 expression on >=1% of tumor cells or >=5% of immune cells.

  15. Number of Participants With CD8 Expression for PFS (Based on BICR Assessment) and for OS [ Time Frame: Biomarkers are measured only at screening. ]
    Tumor infiltrating CD8 positive (CD8+) T lymphocytes was assessed by immunohistochemistry. Participants were considered positive for CD8 T cells if their baseline tissue sample demonstrated presence of >=1% CD8+ cells across the area of the tumor.

  16. Number of Participants With Improved, Stable and Deterioration Based on 10-Point Change for EORTC QLQ-C30 Global QoL [ Time Frame: Day 1 of Cycle 1, Day 1 of each subsequent cycle, end of treatment/withdrawal visit and the 30, 60 and 90 days safety follow up visits, based on cutoff date: 19 September 2018. ]
    The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) is a 30 question survey and includes 5 functional domain subscales, global health status/quality of life, disease/treatment related symptoms, and the perceived financial impact of disease. Higher scores are reflective of a greater presence of symptoms.

  17. Time to Deterioration in Abdominal/GI Symptom Subscale of EORTC QLQ-OV28 [ Time Frame: From Day 1 of Cycle 1 to prior to end of treatment/withdrawal visit, based on cutoff date: 19 September 2018. ]
    The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Ovarian Cancer 28 (EORTC QLQ-OV28) is a 28 item instrument with 7 functional domain subscales. Time to deterioration was defined as the time from randomization to the first time the participant's score showed a 15-point or higher increase in the score of the abdominal/GI symptom subscale of the EORTC QLQ-OV28.

  18. Change From Baseline in EQ-VAS Score at End of Treatment [ Time Frame: Baseline and end of treatment/withdrawal visit ]
    The EuroQol- 5 Dimensions- 5 Levels (EQ-5D-5L) questionnaire consists of the EQ-5D-5L descriptive system and a visual analogue scale (the EuroQol-visual analogue scale [EQ-VAS]). The respondent's self-rated health is assessed on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) by the EQ-VAS.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02580058


Locations
Show Show 298 study locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Statistical Analysis Plan  [PDF] December 13, 2017
Study Protocol  [PDF] December 15, 2016

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02580058    
Other Study ID Numbers: B9991009
2015-003091-77 ( EudraCT Number )
JAVELIN OVARIAN 200 ( Other Identifier: Alias Study Number )
First Posted: October 20, 2015    Key Record Dates
Results First Posted: November 19, 2019
Last Update Posted: November 19, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
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
Keywords provided by Pfizer:
platinum resistant
platinum refractory
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action