Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Neoplasms
Conditions
Keywords
Ovarian Cancer, Primary Fallopian Tube Cancer, Peritoneal Cancer
Brief summary
The purpose of this study is to determine if an investigational drug called MORAb-003 is useful by itself or when used with other approved cancer drugs in treating women with ovarian cancer. MORAb-003 is a monoclonal antibody directed against an antigen on most ovarian cancers.
Detailed description
MORAb-003 is a monoclonal antibody that has the potential to be an effective agent against epithelial ovarian cancer (including primary fallopian tube and peritoneal adenocarcinoma) either alone or in combination with other drugs. MORAb-003 works by a different mechanism from other cancer therapeutics and has been shown to be well tolerated. This study allows the opportunity to determine if MORAb-003 can work either as a single agent 1. to treat a CA125-only relapse, or 2. in combination with standard platinum and taxane chemotherapy to treat a symptomatic relapse, and 3. to prolong a second response to chemotherapy.
Interventions
DRUGFarletuzumab
Weekly Farletuzumab infusions Dose dependent on dosing group
DRUGChemo Plus Far
Chemo+Far: paclitaxel 175 mg/m2 (or docetaxel, 75 mg/m2) plus carboplatin area under the concentration-time curve (AUC) 5-6 intravenously (IV) on Day 1 of a 21-day cycle plus farletuzumab, 100 mg/m2.
Sponsors
Morphotek
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female subjects at least 18 years of age, with a histologically confirmed diagnosis of non-mucinous epithelial ovarian cancer (including fallopian tube and primary peritoneal cancer) in first relapse after a first remission of 6 to 18 months duration. * Subjects must have undergone surgery. Subjects must have received primary chemotherapy, including at least one platinum agent. * Subject is eligible for retreatment with the same chemotherapy regimen that was used to induce remission (Exception: may reduce the dose of or discontinue taxane if contraindicated due to neurotoxicity.) * CA125 must have been elevated prior to original chemotherapy. * CA125 must be elevated at the time of relapse. * Life expectancy greater than or equal to 6 months, as estimated by the investigator. * Eastern Cooperative Oncology Group performance status of 0, 1 or 2 * Subjects must consent to use a medically acceptable method of contraception throughout the study period and for 28 days after final MORAb-003 administration, unless surgically sterile. * Any significant concomitant medical conditions must be well controlled and stable in the opinion of the investigator for at least 30 days prior to Study Day 1. * Laboratory and clinical results within the 2 weeks prior to Study Day 1 as follows: * Absolute neutrophil count (ANC) ≥ 1.2 x 10e9/L * Platelet count ≥ 100 x 10e9/L * Hemoglobin ≥ 8 g/dL * Subject must be willing and able to provide written informed consent. Translations of informed consent information may be provided, subject to the local institutional review board's (IRB's) policy.
Exclusion criteria
* Known central nervous system (CNS) tumor involvement. * Evidence of other active malignancy requiring treatment. * Clinically significant heart disease (e.g., congestive heart failure of New York Heart Association Class III or IV, angina not well controlled by medication, or myocardial infarction within 6 months). * Electrocardiogram (ECG) demonstrating clinically significant arrhythmias (Exception: Subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia \[SVT\], are eligible). * Active serious systemic disease, including active bacterial or fungal infection. * Active hepatitis or HIV infection. * Treatment within three months with immunomodulatory therapy (e.g. interferons, immunoglobulin therapy, interleukin 1 receptor antagonist \[IL-1RA\] or systemic corticosteroids). Short term systemic corticosteroids or topical or intra-articular steroids are acceptable, subject to the judgment of the investigator. * Treatment with a monoclonal antibody therapy AND have evidence of an immune or allergic reaction or documented HAHA. * Maintenance of first remission by taxane or other chemotherapeutic agent(s). * Initiation or planned initiation of cancer therapy not given to induce primary remission. Substitutions of agents materially similar to those used in the original regimen are permissible. * Breast-feeding, pregnant, or likely to become pregnant during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serologic Response (Change in CA125 Level) | Baseline to response (up to 30 weeks) | Defined using modified Gynecologic Cancer Intergroup (GCIG) criteria: Number of participants who achieved a 50% response = \>50% decrease from baseline CA-125 (higher of 2 pretreatment CA-125 assessments and the level must be at least 52.5 kU/L). |
| Serologic Response (Change in Cancer Antigen [CA-125] Level) | Baseline to response (up to 27 weeks) | Defined using modified Gynecologic Cancer Intergroup (GCIG) criteria: Number of participants who had a 50% response = \>50% decrease from baseline CA-125 (higher of 2 pretreatment CA-125 assessments and the level must be at least 52.5 kU/L). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | Baseline to response (up to 44 months) | The Overall Response Rate (ORR) will be determined by applying standard RECIST criteria to objective measures of disease, such as CT or MRI scans. Participants will be assigned to one of the categories of change in disease status, namely, complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). ORR is defined as the percentage of participants with objective evidence of CR or PR. |
| Time to Serologic Response (Change in CA-125 Level) | Baseline to response (up to 27 weeks) | Time to Serologic Response is defined as the time (weeks) from the date of first farletuzumab infusion to first documentation of 50% decrease from baseline CA-125 (higher of 2 pretreatment CA-125 assessments and at least twice the upper limit of normal) and then confirmed after 21 days. |
| Percentage of Participants Who Had a Prolongation of Remission | Baseline to response (up to 44 months) | Percentage of participants whose second remission was longer than their first remission. The length of remission will be determined for participants who attain CR or PR (or SD and investigator's assessment of clinical benefit). Prolongation of remission will be defined as a length of remission occurring on this study that is ≥ 1 day longer than the length of remission to the original therapy. The length of remission on this study (second remission) will be defined as the amount of time from the date of first CR or PR to the end of this remission. |
| Progression-free Survival (PFS) | Baseline to response (up to 44 months) | PFS is defined for participants treated in Chemo Plus Far as the time (in months) from date of first dose in Chemo Plus Far until date of the first observation of progression based on first date of the CA-125 \>2 X ULN on two occasions, or date of death, whatever the cause. If progression or death is not observed for a participant, the PFS time is censored at the later date of last tumor assessment or CA125 assessment without evidence of progression prior to the date of initiation of further anti-tumor treatment. |
| Duration of Serologic Response (CA-125) | Baseline to response (up to 44 months) | Calculated as the time from the first documentation of 50% or greater reduction in CA-125 to the first documentation of serologic progression or death due to any cause. Serologic progression was defined as the first date of the CA-125 level being \>2 X ULN on two occasions. |
Countries
Germany, United States
Participant flow
Recruitment details
The first 6 participants enrolled in this study were dosed at farletuzumab, 37.5 mg/m2. The next 6 participants were dosed at farletuzumab, 62.5 mg/m2. The remaining participants received farletuzumab, 100 mg/m2.
Participants by arm
| Arm | Count |
|---|---|
| Far Only and Chemo Plus Far and Maintenance Far Only Farletuzumab only (Far Only): farletuzumab, 100 milligrams (mg)/square meter (m2).
Chemo+Far: paclitaxel 175 mg/m2 (or docetaxel, 75 mg/m2) plus carboplatin area under the concentration-time curve (AUC) 5-6 intravenously (IV) on Day 1 of a 21-day cycle plus farletuzumab, 100 mg/m2.
Maintenance Far Only: farletuzumab, 100 milligrams (mg)/square meter (m2) for those subjects who completed the Period, Chemo Plus Far. | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period 1 | Lack of Efficacy | 5 | 0 | 0 |
| Period 1 | Physician Decision | 1 | 0 | 0 |
| Period 1 | Withdrawal by Subject | 1 | 0 | 0 |
| Period 2 | Adverse Event | 0 | 3 | 0 |
| Period 2 | Lack of Efficacy | 0 | 5 | 0 |
| Period 2 | Other | 0 | 1 | 0 |
| Period 2 | Physician Decision | 0 | 1 | 0 |
| Period 2 | Withdrawal by Subject | 0 | 1 | 0 |
| Period 3 | Adverse Event | 0 | 0 | 1 |
| Period 3 | Death | 0 | 0 | 1 |
| Period 3 | Lack of Efficacy | 0 | 0 | 24 |
| Period 3 | Other | 0 | 0 | 3 |
| Period 3 | Physician Decision | 0 | 0 | 1 |
| Period 3 | Withdrawal by Subject | 0 | 0 | 3 |
Baseline characteristics
| Characteristic | Far Only and Chemo Plus Far and Maintenance Far Only |
|---|---|
| Age, Continuous | 63.2 years STANDARD_DEVIATION 11.66 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants |
| Race/Ethnicity, Customized Asian | 5 participants |
| Race/Ethnicity, Customized Black or African American | 1 participants |
| Race/Ethnicity, Customized Hispanic | 4 participants |
| Race/Ethnicity, Customized More than one race | 0 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 participants |
| Race/Ethnicity, Customized White | 44 participants |
| Sex: Female, Male Female | 54 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 54 / 54 |
| serious Total, serious adverse events | 20 / 54 |
Outcome results
Primary
Serologic Response (Change in CA125 Level)
Defined using modified Gynecologic Cancer Intergroup (GCIG) criteria: Number of participants who achieved a 50% response = \>50% decrease from baseline CA-125 (higher of 2 pretreatment CA-125 assessments and the level must be at least 52.5 kU/L).
Time frame: Baseline to response (up to 30 weeks)
Population: All participants enrolled to initial farletuzumab only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Far Only | Serologic Response (Change in CA125 Level) | 2 participants |
Primary
Serologic Response (Change in Cancer Antigen [CA-125] Level)
Defined using modified Gynecologic Cancer Intergroup (GCIG) criteria: Number of participants who had a 50% response = \>50% decrease from baseline CA-125 (higher of 2 pretreatment CA-125 assessments and the level must be at least 52.5 kU/L).
Time frame: Baseline to response (up to 27 weeks)
Population: All participants enrolled to chemotherapy plus farletuzumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Far Only | Serologic Response (Change in Cancer Antigen [CA-125] Level) | 41 participants |
Secondary
Duration of Serologic Response (CA-125)
Calculated as the time from the first documentation of 50% or greater reduction in CA-125 to the first documentation of serologic progression or death due to any cause. Serologic progression was defined as the first date of the CA-125 level being \>2 X ULN on two occasions.
Time frame: Baseline to response (up to 44 months)
Population: All participants enrolled to initial chemotherapy plus farletuzumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Far Only | Duration of Serologic Response (CA-125) | NA Months |
Secondary
Overall Response Rate
The Overall Response Rate (ORR) will be determined by applying standard RECIST criteria to objective measures of disease, such as CT or MRI scans. Participants will be assigned to one of the categories of change in disease status, namely, complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). ORR is defined as the percentage of participants with objective evidence of CR or PR.
Time frame: Baseline to response (up to 44 months)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Far Only | Overall Response Rate | Complete Response | 6.8 percentage of participants |
| Far Only | Overall Response Rate | Partial Response | 63.6 percentage of participants |
| Far Only | Overall Response Rate | Stable Disease | 20.5 percentage of participants |
| Far Only | Overall Response Rate | Progressive Disease | 4.5 percentage of participants |
| Far Only | Overall Response Rate | Not Evaluable | 6.8 percentage of participants |
Secondary
Percentage of Participants Who Had a Prolongation of Remission
Percentage of participants whose second remission was longer than their first remission. The length of remission will be determined for participants who attain CR or PR (or SD and investigator's assessment of clinical benefit). Prolongation of remission will be defined as a length of remission occurring on this study that is ≥ 1 day longer than the length of remission to the original therapy. The length of remission on this study (second remission) will be defined as the amount of time from the date of first CR or PR to the end of this remission.
Time frame: Baseline to response (up to 44 months)
Population: All participants who received chemotherapy plus farletuzumab as well as those who continued on maintenance farletuzumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Far Only | Percentage of Participants Who Had a Prolongation of Remission | 25.6 percentage of participants |
Secondary
Progression-free Survival (PFS)
PFS is defined for participants treated in Chemo Plus Far as the time (in months) from date of first dose in Chemo Plus Far until date of the first observation of progression based on first date of the CA-125 \>2 X ULN on two occasions, or date of death, whatever the cause. If progression or death is not observed for a participant, the PFS time is censored at the later date of last tumor assessment or CA125 assessment without evidence of progression prior to the date of initiation of further anti-tumor treatment.
Time frame: Baseline to response (up to 44 months)
Population: All participants who received chemotherapy plus farletuzumab as well as those who continued on maintenance farletuzumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Far Only | Progression-free Survival (PFS) | 10.2 Months |
Secondary
Time to Serologic Response (Change in CA-125 Level)
Time to Serologic Response is defined as the time (weeks) from the date of first farletuzumab infusion to first documentation of 50% decrease from baseline CA-125 (higher of 2 pretreatment CA-125 assessments and at least twice the upper limit of normal) and then confirmed after 21 days.
Time frame: Baseline to response (up to 27 weeks)
Population: All participants enrolled to intial chemotherapy plus farletuzumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Far Only | Time to Serologic Response (Change in CA-125 Level) | 3.3 Weeks |