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NCT00849667

Efficacy and Safety of Farletuzumab (MORAb-003) in Combination With Carboplatin and Taxane in Participants With Platinum-sensitive Ovarian Cancer in First Relapse

Terminated Phase 3 Results posted Last updated 30 December 2022
What this trial tests

Phase 3 trial testing Farletuzumab in Ovarian Cancer in 1,100 participants. Terminated before completion.

Timeline
16 April 2009
Primary endpoint
31 December 2012
12 April 2013

Quick facts

Lead sponsorMorphotek
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment1,100
Start date16 April 2009
Primary completion31 December 2012
Estimated completion12 April 2013
Sites375 locations across Hong Kong, Italy, Japan, Taiwan, Poland, South Korea, Philippines, Netherlands

Drugs / interventions tested

Conditions studied

Sponsor

Morphotek — full company profile →

Who can join

18 and older, female only, with Ovarian Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-free Survival (PFS) Primary · From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months)

PFS was defined as the time (in months) from the date of randomization to the date of the first observation of progression based on the independent radiologic assessment (modified response evaluation criteria in solid tumors \[RECIST\]), or date of death, whatever the cause. As per RECIST, disease progression was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions. If progression or death was not observed for a participant, the PFS time was censored at the date of the last tumor assessment

GroupValue95% CI
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin9.58.6 – 10.2
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin9.78.8 – 10.4
Placebo Plus Taxane and Carboplatin9.08.4 – 9.8
Overall Survival (OS) Secondary · From the date of randomization until date of death from any cause, or study termination by sponsor, whichever came first (up to 48 months)

OS was defined as the time (in months) from the date of randomization to the date of death, due to any cause. If death was not observed for a participant, the survival time was censored on the last date the participant was known to be alive or the cutoff date, whichever was earlier.

GroupValue95% CI
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin28.726.6 – 33.5
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin32.126.7 – 35.0
Placebo Plus Taxane and Carboplatin29.125.6 – 30.7
Cancer Antigen-125 (CA-125) Progression-Free Survival Secondary · From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months)

CA-125 PFS was defined as the time (in months) from the date of randomization until the date of the first observation of progression based on the Rustin criteria, or date of death, whatever the cause. If progression or death was not observed for a participant, the CA-125 PFS time was censored at the date of the last CA-125 assessment without evidence of progression before the date of initiation of further antitumor treatment or the "primary analysis cut off" date, whichever was earlier. Based on Rustin criteria, progressive disease (PD) was a rise in CA125 since beginning of consolidation or p

GroupValue95% CI
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin13.211.8 – 14.4
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin18.112.7 – NA
Placebo Plus Taxane and Carboplatin12.011.1 – 14.6
Progression-Free Survival Based on Gynecologic Cancer InterGroup (GCIG) Criteria Secondary · From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months)

PFS using GCIG criteria was defined as time (in months) from date of randomization until date of first observation of progression based on GCIG criteria, or date of death, whatever the cause. If progression or death was not observed for a participant, GCIG PFS time was censored at later date of last tumor assessment or CA-125 assessment without evidence of progression before date of initiation of further antitumor treatment or the "primary analysis cut off" date, whichever was earlier. Disease progression per GCIG: Participants with elevated CA-125 pretreatment and normalisation of CA-125 must

GroupValue95% CI
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin8.88.4 – 9.7
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin8.68.3 – 9.5
Placebo Plus Taxane and Carboplatin8.48.2 – 9.0
Percentage of Participants With Length of Second Remission Greater Than First Remission Secondary · From the date of last dose of platinum-based chemotherapy to date of relapse and date of last dose of platinum-based chemotherapy to first observation of progression (up to 48 months)

Length of first remission was defined as a.) the period of time (in months) from the date of completion of previous platinum-based chemotherapy until date of first relapse (that is, first observation of progression). It was assumed that the date of first relapse was the earlier of progression by CA-125 or progression by radiologic assessment, as judged by the investigator using GCIG criteria. b.) the period of time (in months) from the date of completion of previous platinum-based chemotherapy (used prior to study entry) until date of randomization. The length of the second remission was defin

GroupValue95% CI
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin4.01.8 – 7.8
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin6.53.5 – 10.9
Placebo Plus Taxane and Carboplatin4.52.1 – 8.3
Percentage of Participants With Objective Response Secondary · From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 48 months)

Objective response was defined as either a confirmed complete response (CR) or confirmed partial response (PR) as assessed by investigator based on response evaluation criteria in solid tumors version 1.1 (RECIST version 1.1). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis less than (\<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.

GroupValue95% CI
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin57.652.4 – 62.7
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin58.253.0 – 63.3
Placebo Plus Taxane and Carboplatin55.850.5 – 60.9
Duration of Tumor Response Secondary · From the first date of confirmed objective response (CR or PR) to first date of progression or death due to any cause (up to 48 months)

Duration of response was defined as the time (in months) from first documentation of objective response (confirmed CR or PR) to the first documentation of objective tumor progression or death due to any cause. Duration of response was derived only for those participants with objective evidence of confirmed CR or PR.

GroupValue95% CI
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin8.07.6 – 9.2
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin8.97.7 – 9.7
Placebo Plus Taxane and Carboplatin7.67.1 – 8.7
Time to Tumor Response (TTR) Secondary · From the date of randomization to first documentation of objective response (up to 48 months)

Time to tumor response was defined as the time (in months) from the date of randomization to first documentation of objective tumor response. Time to tumor response was derived for those participants with objective evidence of CR or PR.

GroupValue95% CI
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin1.51.4 – 1.7
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin1.51.4 – 1.7
Placebo Plus Taxane and Carboplatin1.51.4 – 1.9
Percentage of Participants With Serologic Response (SR) Secondary · Up to 48 months

SR was defined as either normalization, 75% response, or 50% response using the Rustin criteria. Percentage of participants with 50% SR, 75% SR and SR leading to normalization were reported. A 50% response according to CA-125 was defined as a 50% decrease in serum CA-125 levels, as determined through a series of four CA-125 samples (one baseline sample with an elevated level, the sample that showed a 50% decrease, and a confirmatory sample at the decreased level). A 75% response was established if there had a serial decrease in serum CA-125 levels of 75% over three samples. In both the 50% and

50% SR (Responder)
GroupValue95% CI
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin91.988.1 – 94.9
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin97.494.8 – 99.0
Placebo Plus Taxane and Carboplatin92.388.4 – 95.2
75% SR (Responder)
GroupValue95% CI
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin86.181.4 – 90.0
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin85.781.0 – 89.6
Placebo Plus Taxane and Carboplatin82.076.9 – 86.4
SR leading to normalization (Responder)
GroupValue95% CI
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin65.259.2 – 70.8
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin64.858.9 – 70.5
Placebo Plus Taxane and Carboplatin59.953.8 – 65.8
Duration of 50% Serologic Response Secondary · From the first date of documentation of response to first documentation of serologic progression or death due to any cause (up to 48 months)

Duration of SR was defined as the time (in months) from first documentation of response to the first documentation of 50% serologic progression or death due to any cause. For responding participants who did not have serologic progression or did not die and who 1) were either still on study at the time of an analysis, 2) were given antitumor treatment other than study treatment, or 3) were withdrawn from study follow-up before documentation of serologic progression, the duration of SR was censored at the last date the participant was known to be without serologic progression. A 50% response acc

GroupValue95% CI
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin10.79.7 – 12.0
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin12.010.4 – 16.7
Placebo Plus Taxane and Carboplatin9.99.0 – 11.5
Time to 50% Serologic Response (TSR) Secondary · From the date of randomization to first documentation of 50% SR (up to 48 months)

TSR was defined as the time (in months) from the date of randomization to first documentation of 50% SR. A 50% response according to CA-125 was defined as a 50% decrease in serum CA-125 levels, as determined through a series of three CA-125 samples (one baseline sample with an elevated level, the sample that showed a 50% decrease, and a confirmatory sample at the decreased level).

GroupValue95% CI
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin1.00.9 – 1.0
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin0.90.9 – 1.0
Placebo Plus Taxane and Carboplatin1.21.0 – 1.4
Percentage of Participants With Clinical Benefit Secondary · Up to 48 months

Clinical benefit was defined as a confirmed CR or a confirmed PR, or stable disease (SD) using RECIST 1.0 criteria. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR was defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference small

GroupValue95% CI
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin68.9
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin66.4
Placebo Plus Taxane and Carboplatin64.6

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 48 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin
Serious: 140/376 (37%)
Deaths: 143/376
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin
Serious: 130/363 (36%)
Deaths: 119/363
Placebo Plus Taxane and Carboplatin
Serious: 112/352 (32%)
Deaths: 121/352

Serious adverse events (229 terms)

ReactionSystem1.25 mg/kg Farletuzumab Pl…2.5 mg/kg Farletuzumab Plu…Placebo Plus Taxane and Ca…
NeutropeniaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
AnaemiaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
VomitingGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Pulmomary embolismRespiratory, thoracic and mediastinal disorders
AscitesGastrointestinal disorders
NauseaGastrointestinal disorders
Drug hypersensitivityImmune system disorders
Intestinal obstructionGastrointestinal disorders
PyrexiaGeneral disorders
FatigueGeneral disorders
IleusGastrointestinal disorders
PneumoniaInfections and infestations
Urinary tract infectionInfections and infestations
Small intestine obstructionGastrointestinal disorders
SubileusGastrointestinal disorders
Disease progressionGeneral disorders
AstheniaGeneral disorders
Neutropenic sepsisInfections and infestations
DehydrationMetabolism and nutrition disorders
Lower respiratory tract infectionInfections and infestations
LeukopeniaBlood and lymphatic system disorders
Other adverse events (64 terms — click to expand)

ReactionSystem1.25 mg/kg Farletuzumab Pl…2.5 mg/kg Farletuzumab Plu…Placebo Plus Taxane and Ca…
AlopeciaSkin and subcutaneous tissue disorders
NauseaGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
FatigueGeneral disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
Abdominal painGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Peripheral sensory neuropathyNervous system disorders
AstheniaGeneral disorders
HeadacheNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
LeukopeniaBlood and lymphatic system disorders
MyaligiaMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
PyrexiaGeneral disorders
Back painMusculoskeletal and connective tissue disorders
DysgeusiaNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Drug hypersensitivityImmune system disorders
PruritusSkin and subcutaneous tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
RashSkin and subcutaneous tissue disorders
Urinary tract infectionInfections and infestations
Abdominal pain upperGastrointestinal disorders
InsomniaPsychiatric disorders
NasopharyngitisInfections and infestations
DyspepsiaGastrointestinal disorders
Neuropathy peripheralNervous system disorders
Oedema peripheralGeneral disorders
Upper respiratory tract infectionInfections and infestations
StomatitisGastrointestinal disorders
HypokalaemiaMetabolism and nutrition disorders
HypomagnesaemiaMetabolism and nutrition disorders
PainGeneral disorders
Bone painMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Neutropenia, Febrile neutropenia, Anaemia, Thrombocytopenia, Abdominal pain, Vomiting, Diarrhoea, Pulmomary embolism.

Data from ClinicalTrials.gov NCT00849667 adverse events section.

Sponsor's own description

This research is being done to find out if Carboplatin and Taxane works better alone or when given with an experimental drug called MORAb-003(farletuzumab) in subjects with first platinum sensitive relapsed ovarian cancer.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Advances in ovarian cancer therapy.
    Cortez AJ, Tudrej P, Kujawa KA, Lisowska KM. · · 2018 · cited 417× · PMID 29249039 · DOI 10.1007/s00280-017-3501-8
  2. Latest research and treatment of advanced-stage epithelial ovarian cancer.
    Coleman RL, Monk BJ, Sood AK, Herzog TJ. · · 2013 · cited 412× · PMID 23381004 · DOI 10.1038/nrclinonc.2013.5
  3. Targeting folate receptor alpha for cancer treatment.
    Cheung A, Bax HJ, Josephs DH, Ilieva KM, et al · · 2016 · cited 298× · PMID 27248175 · DOI 10.18632/oncotarget.9651
  4. Antibody-based therapeutics to watch in 2011.
    Reichert JM. · · 2011 · cited 161× · PMID 21051951 · DOI 10.4161/mabs.3.1.13895
  5. Targeted drug delivery via folate receptors in recurrent ovarian cancer: a review.
    Marchetti C, Palaia I, Giorgini M, De Medici C, et al · · 2014 · cited 92× · PMID 25031539 · DOI 10.2147/ott.s40947
  6. Which are the antibodies to watch in 2013?
    Reichert JM. · · 2013 · cited 83× · PMID 23254906 · DOI 10.4161/mabs.22976
  7. Evidence for a time-dependent association between FOLR1 expression and survival from ovarian carcinoma: implications for clinical testing. An Ovarian Tumour Tissue Analysis consortium study.
    Köbel M, Madore J, Ramus SJ, Clarke BA, et al · · 2014 · cited 82× · PMID 25349970 · DOI 10.1038/bjc.2014.567
  8. Antibodies to watch in 2010.
    Reichert JM. · · 2010 · cited 68× · PMID 20065640 · DOI 10.4161/mabs.2.1.10677

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