Recurrent Ovarian Cancer, Fallopian Tube Carcinoma, Primary Peritoneal Carcinoma
Conditions
Brief summary
The purpose of this study is to evaluate the safety and efficacy of TRC105 in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
Detailed description
Angiogenesis plays a central role in the progression of epithelial ovarian cancer. In mouse models, VEGF-inhibitors diminish ovarian tumor growth, metastasis and malignant ascites formation. Independent Phase 2 trials have demonstrated single-agent activity for bevacizumab in recurrent ovarian cancer, and randomized controlled Phase 3 trials are ongoing in the first-line setting (GOG 0218 and ICON-7) and for recurrent disease (GOG 0213, OCEANS). TRC105 is an antibody to CD105, an important non-VEGF angiogenic target on vascular endothelial cells. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models. In a Phase 1 study of advanced solid tumors, TRC105 therapy caused a global reduction in angiogenic biomarkers and reduced tumor burden at doses that were well-tolerated. We hypothesize that TRC105 will have single-agent activity in recurrent ovarian cancer. By targeting a non-VEGF pathway, TRC105 has the potential to complement VEGF inhibitors which could represent a major advance in ovarian cancer therapy.
Interventions
BIOLOGICALCarotuximab (TRC105)
Carotuximab (TRC105) 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle
Sponsors
Tracon Pharmaceuticals Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma * Measurable disease per RECIST 1.1 * At least one target lesion per RECIST 1.1 * Patients must have GOG Performance Status of 0 or 1 * Patients must have a life expectancy of ≥ 3 months * Resolution of all acute toxic effects of prior therapy * Free of active infection requiring antibiotics * Must have had one prior platinum-based chemotherapeutic regimen for management of primary disease * Patients could have received one additional cytotoxic regimen for management of recurrent disease * Prior therapy directed at the malignant tumor, including hormonal and immunologic agents, must be discontinued at least three weeks prior to registration. Continuation of hormone replacement therapy is permitted. * Adequate bone marrow function, renal function, hepatic function, neurologic function, blood coagulation parameters * Negative serum pregnancy test and effective form of contraception for patients of childbearing potential
Exclusion criteria
* Previous treatment with TRC105 * Current treatment on another therapeutic clinical trial * Receipt of an investigational agent within 28 days of starting study treatment * Serious, non-healing wounds, ulcers, or bone fractures. * Active bleeding or pathologic conditions that carry a high risk of bleeding * Patients with tumor involving major vessels or transmural bowel wall involvement by tumor * Use of thrombolytic or anticoagulant agents (except heparin to maintain i.v. catheters) within 10 days prior to the first dose of TRC105 * History of deep venous thrombosis (DVT)(except patients who have received adequate anticoagulation are eligible, and may continue on anticoagulation if appropriate) * History of peptic ulcer disease or erosive gastritis within the past 6 months * Known active viral or nonviral hepatitis * History or evidence of CNS disease * Clinically significant cardiovascular disease * Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human, chimeric, or humanized antibodies * Pregnant or nursing * Under the age of 18 * Patients with or with anticipation of invasive procedures including major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to treatment with TRC105 * History of other invasive malignancies, except non-melanoma skin cancer and other cancers that have been treated with no evidence of disease within the last 3 years * History of primary endometrial cancer diagnosed within the last 5 years, unless all of the following conditions are met: Stage not greater than I-B; no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other FIGO Grade 3 lesions * Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last five years are excluded. Patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed \> 3 years prior to registration, and patient remains free of recurrent or metastatic disease * Prior radiotherapy to any portion of the abdominal cavity or pelvis * Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration and/or nutrition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival Rate After 6 Months of Treatment on Study | 6 months | Number of patients ongoing within the study who have not progressed after 6 months of treatment |
| Proportion of Patients Who Have Objective Tumor Response | Every 2 cycles | Proportion of patients who have objective tumor response (complete or partial) by RECIST 1.1 |
| Adverse Events | 28 days | Frequency of adverse events as assessed by NCI CTCAE (Version 4.0) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severity of Adverse Events | 28 days post last dose of TRC105 | Severity of adverse events by NCI CTCAE |
| CA-125 Response Rate | Every 2 cycles | CA-125 response rate by GCIG criteria |
| Overall Survival | 2 years | Median overall survival |
| Serum Concentrations of TRC105 | Cycle 1 Day 15 | Median peak and trough concentration of TRC105 by ELISA in ug/mL |
| TRC105 Immunogenicity | 1 year | TRC105 Anti-Drug Antibody (ADA) Immunogenicity by ELISA |
Countries
United States
Participant flow
Recruitment details
Patients were screened and enrolled at 7 US sites
Participants by arm
| Arm | Count |
|---|---|
| TRC105 Chimeric monoclonal antibody (TRC105) to CD105: 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | TRC105 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 59.8 Years |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 23 |
| other Total, other adverse events | 23 / 23 |
| serious Total, serious adverse events | 6 / 23 |
Outcome results
Primary
Adverse Events
Frequency of adverse events as assessed by NCI CTCAE (Version 4.0)
Time frame: 28 days
Population: All patients who received at least a portion of a dose of TRC105.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TRC105 | Adverse Events | Anemia (Grade 3 Suspected Reaction) | 4 Participants |
| TRC105 | Adverse Events | Fatigue (Grade 3 Suspected Reaction) | 1 Participants |
| TRC105 | Adverse Events | Headache (Grade 3 Suspected Reaction) | 2 Participants |
| TRC105 | Adverse Events | Migraine (Grade 3 Suspected Reaction) | 1 Participants |
| TRC105 | Adverse Events | Epistaxis (Grade 3 Suspected Reaction) | 1 Participants |
Primary
Progression-free Survival Rate After 6 Months of Treatment on Study
Number of patients ongoing within the study who have not progressed after 6 months of treatment
Time frame: 6 months
Population: This population will include all patients enrolled in the study who receive at least 1 dose of TRC105 study medication and who undergo at least one on study efficacy assessment or expire due to progressive disease prior to the first efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TRC105 | Progression-free Survival Rate After 6 Months of Treatment on Study | 0 participants |
Primary
Proportion of Patients Who Have Objective Tumor Response
Proportion of patients who have objective tumor response (complete or partial) by RECIST 1.1
Time frame: Every 2 cycles
Population: This population will include all patients enrolled in the study who receive at least 1 dose of TRC105 study medication and who undergo at least one on study efficacy assessment or expire due to progressive disease prior to the first efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TRC105 | Proportion of Patients Who Have Objective Tumor Response | 0 participants |
Secondary
CA-125 Response Rate
CA-125 response rate by GCIG criteria
Time frame: Every 2 cycles
Population: All patients who received at least a portion of a dose of TRC105
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TRC105 | CA-125 Response Rate | CA-125 Decrease | 7 participants |
| TRC105 | CA-125 Response Rate | CA-125 Increase | 16 participants |
Secondary
Overall Survival
Median overall survival
Time frame: 2 years
Population: Data not collected
Secondary
Serum Concentrations of TRC105
Median peak and trough concentration of TRC105 by ELISA in ug/mL
Time frame: Cycle 1 Day 15
Population: All patients who received at least a portion of a TRC105 dose
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TRC105 | Serum Concentrations of TRC105 | Median Trough Concentration Cycle 1 Day 15 | 47.4 ug/mL |
| TRC105 | Serum Concentrations of TRC105 | Median Peak Concentration Cycle 1 Day 15 | 274.5 ug/mL |
Secondary
Severity of Adverse Events
Severity of adverse events by NCI CTCAE
Time frame: 28 days post last dose of TRC105
Population: All patients who received at least a portion of a dose of TRC105.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TRC105 | Severity of Adverse Events | Serious Adverse Events | 6 participants |
| TRC105 | Severity of Adverse Events | TRC105 Related Serious Adverse Events | 1 participants |
| TRC105 | Severity of Adverse Events | No Serious Adverse Events | 16 participants |
Secondary
TRC105 Immunogenicity
TRC105 Anti-Drug Antibody (ADA) Immunogenicity by ELISA
Time frame: 1 year
Population: All patients that received at least a portion of TRC105
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TRC105 | TRC105 Immunogenicity | Patients with Positive Treatment Emergent ADA | 7 Participants |
| TRC105 | TRC105 Immunogenicity | Patients with Negative Treatment Emergent ADA | 10 Participants |