Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer
Conditions
Keywords
stage II ovarian epithelial cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, primary peritoneal cavity cancer, fallopian tube cancer
Brief summary
RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. PURPOSE: A phase I trial to study the side effects of vaccine therapy in patients with ovarian epithelial, primary peritoneal, or fallopian tube cancer.
Detailed description
OBJECTIVES: * Determine the safety of NY-ESO-1b peptide vaccine and Montanide® ISA-51 in patients with ovarian epithelial, primary peritoneal, or fallopian tube cancer. * Determine the immunologic profile (NY-ESO-1 antibody, CD8+ cells, and delayed-type hypersensitivity) induced by this regimen in these patients. OUTLINE: This is an open-label study. Patients receive NY-ESO-1b peptide vaccine emulsified with Montanide® ISA-51 subcutaneously once every 3 weeks on weeks 1, 4, 7, 10, and 13 in the absence of disease progression or unacceptable toxicity. Patients are followed at 3 weeks (week 16) and then every 6-12 weeks for 2 years or until disease progression.
Interventions
BIOLOGICALNY-ESO-1 peptide vaccine
NY-ESO-1b peptide 100 μg mixed with 0.5 mL of Montanide® ISA-51
Sponsors
National Cancer Institute (NCI)
Ludwig Institute for Cancer Research
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically documented epithelial carcinoma arising in the ovary, fallopian tube, or peritoneum, from Stage II-IV at diagnosis, receiving initial cytoreductive surgery and chemotherapy with at least one platinum-based chemotherapy regimen. 2. High risk feature defined as suboptimal primary debulking (remaining tumor masses with diameter ≥ 1.0 cm) or failure to normalize CA125 during primary therapy by the end of the third cycle or positive second-look surgery. 3. Patients must be in complete clinical remission defined as CA125 \< 35 units, negative physical examination and no definite evidence of disease by computed tomography (CT) of the abdomen and pelvis. Lymph nodes and/or soft tissue abnormalities ≤ 1.0 cm that are often present in the pelvis may not be considered definite evidence of disease. 4. Expected survival of at least 6 months. 5. Karnofsky performance scale ≥60%. 6. Within the last 2 weeks prior to study day 1, vital laboratory parameters should be within normal range, except for the following laboratory parameters, which should be within the ranges specified: * Absolute neutrophil count (ANC) ≥1000/mm\^3 * Platelets ≥ 80,000/mm\^3 * Creatinine ≤ 1.5mg/dL * Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), and total bilirubin all \< 2.5 x upper limit of normal (ULN) 7 Age ≥ 18 years. 8\. Able and willing to give valid written informed consent. 9. HLA A02 positive.
Exclusion criteria
Patients were excluded from the study for any of the following reasons: 1. Clinically significant heart disease (NYHA Class III or IV). 2. Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders. 3. Patients with serious intercurrent illness, requiring hospitalization. 4. Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available. 5. Patients taking immunosuppressive drugs such as systemic corticosteroids or non-steroidal anti-inflammatory drugs. 6. Known HIV positivity. 7. Other malignancy within 3 years prior to entry into the study, except for treated nonmelanoma skin cancer and cervical carcinoma in situ. 8. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study. 9. Lack of availability for immunological and clinical follow-up assessments. 10. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment. 11. Pregnancy or breastfeeding. 12. Women of childbearing potential: Refusal or inability to use effective means of contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Dose Limiting Toxicities (DLTs) | up to 16 weeks | Toxicities and adverse events defined by National Cancer Institute Common Toxicity Criteria (CTC) Scale (Version 2.0, published April 30, 1999). DLT defined as: ≥ Grade 2 autoimmune phenomena, asymptomatic bronchospasm or generalized urticaria, or ≥ Grade 3 hematological and non hematological toxicities. To be dose-limiting, an adverse event must be definitely, probably, or possibly related to the administration of the investigational agent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Developing NY-ESO-1 Antibodies After Treatment | up to 16 weeks | Blood samples were obtained at baseline and in weeks 4, 7, 10, 13 and 16 for the assessment of NY-ESO-1 specific antibodies by enzyme-linked immunosorbent assay (ELISA). |
| Number of Patients With NY-ESO-1b-Specific CD8+ T Cells Measured by Tetramer Analysis | up to 16 weeks. | Blood samples were obtained at baseline and at 4, 7, 10. 13 and 16 weeks. Tetramer assays were conducted after presensitization of CD8+ T cells with NY-ESO-1b. Results are presented separately for patients with NY-ESO-1 positive and negative tumors. |
| Number of Patients With NY-ESO-1b-Specific Activated CD8+ T Cells Measured by ELISPOT | up to 16 weeks | Blood samples were obtained at baseline and at 4, 7, 10, 13 and 16 weeks. T cell responses were monitored after the in vitro sensitization with NY-ESO-1b (157-165), modified NY-ESO-1b-A (157-165A), or control peptide influenza matrix 58 to 66. Results are presented separately for patients with NY-ESO-1 positive and negative tumors. |
| Number of Patients With NY-ESO-1b-specific Delayed-type Hypersensitivity (DTH) | up to 16 weeks | NY-ESO-1b-specific delayed-type hypersensitivity (DTH) was measured by number of patients with induration and/or redness at each timepoint. NY-ESO-1b-specific DTH skin reaction was measured at baseline and weeks 7 and 16. The NY-ESO-1b peptide solution (0.1 mg/mL in 8% DMSO) was injected intradermally at a separate site from the vaccination to give a visable and palpable skin depot. The extent and intensity of DTH reactions were documented by measuring visible redness, palpable induration and other signs of local skin irritation or necrosis. Assessment of DTH reaction was performed 48 hours after injection, and the diameter of the reaction was documented. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NY-ESO-1b Peptide With Montanide® ISA-51 Patients received NY-ESO-1b peptide mixed with Montanide® ISA-51 by subcutaneous injections, once every 3 weeks (weeks 1, 4, 7, 10, and 13) for a total of 13 weeks. | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease progression | 1 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | NY-ESO-1b Peptide With Montanide® ISA-51 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| NY-ESO-1 Tumor Expression Negative | 5 Participants |
| NY-ESO-1 Tumor Expression Positive | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Number of Patients With Dose Limiting Toxicities (DLTs)
Toxicities and adverse events defined by National Cancer Institute Common Toxicity Criteria (CTC) Scale (Version 2.0, published April 30, 1999). DLT defined as: ≥ Grade 2 autoimmune phenomena, asymptomatic bronchospasm or generalized urticaria, or ≥ Grade 3 hematological and non hematological toxicities. To be dose-limiting, an adverse event must be definitely, probably, or possibly related to the administration of the investigational agent.
Time frame: up to 16 weeks
Population: All patients who entered the study and received treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NY-ESO-1b Peptide With Montanide® ISA-51 | Number of Patients With Dose Limiting Toxicities (DLTs) | 0 Participants |
Secondary
Number of Patients Developing NY-ESO-1 Antibodies After Treatment
Blood samples were obtained at baseline and in weeks 4, 7, 10, 13 and 16 for the assessment of NY-ESO-1 specific antibodies by enzyme-linked immunosorbent assay (ELISA).
Time frame: up to 16 weeks
Population: All patients who entered the study and received treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NY-ESO-1b Peptide With Montanide® ISA-51 | Number of Patients Developing NY-ESO-1 Antibodies After Treatment | Number of Patients with NY-ESO-1 Antibodies Before and After Treatment | 2 Participants |
| NY-ESO-1b Peptide With Montanide® ISA-51 | Number of Patients Developing NY-ESO-1 Antibodies After Treatment | Number of Patients with No NY-ESO-1 Antibodies Before and After Treatment | 7 Participants |
Secondary
Number of Patients With NY-ESO-1b-Specific Activated CD8+ T Cells Measured by ELISPOT
Blood samples were obtained at baseline and at 4, 7, 10, 13 and 16 weeks. T cell responses were monitored after the in vitro sensitization with NY-ESO-1b (157-165), modified NY-ESO-1b-A (157-165A), or control peptide influenza matrix 58 to 66. Results are presented separately for patients with NY-ESO-1 positive and negative tumors.
Time frame: up to 16 weeks
Population: All patients who entered the study and received treatment.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| NY-ESO-1b Peptide With Montanide® ISA-51 | Number of Patients With NY-ESO-1b-Specific Activated CD8+ T Cells Measured by ELISPOT | Patients with NY-ESO-1 Positive Tumors | Number of patients with CD8+ T cell immunity | 3 Participants |
| NY-ESO-1b Peptide With Montanide® ISA-51 | Number of Patients With NY-ESO-1b-Specific Activated CD8+ T Cells Measured by ELISPOT | Patients with NY-ESO-1 Positive Tumors | Number of patients without CD8+ T cell immunity | 1 Participants |
| NY-ESO-1b Peptide With Montanide® ISA-51 | Number of Patients With NY-ESO-1b-Specific Activated CD8+ T Cells Measured by ELISPOT | Patients with NY-ESO-1 Negative Tumors | Number of patients with CD8+ T cell immunity | 3 Participants |
| NY-ESO-1b Peptide With Montanide® ISA-51 | Number of Patients With NY-ESO-1b-Specific Activated CD8+ T Cells Measured by ELISPOT | Patients with NY-ESO-1 Negative Tumors | Number of patients without CD8+ T cell immunity | 2 Participants |
Secondary
Number of Patients With NY-ESO-1b-Specific CD8+ T Cells Measured by Tetramer Analysis
Blood samples were obtained at baseline and at 4, 7, 10. 13 and 16 weeks. Tetramer assays were conducted after presensitization of CD8+ T cells with NY-ESO-1b. Results are presented separately for patients with NY-ESO-1 positive and negative tumors.
Time frame: up to 16 weeks.
Population: All patients who entered the study and received treatment.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| NY-ESO-1b Peptide With Montanide® ISA-51 | Number of Patients With NY-ESO-1b-Specific CD8+ T Cells Measured by Tetramer Analysis | Patients with NY ESO-1 Positive Tumors | CD8+ T cell immunity by positive tetramer | 3 Participants |
| NY-ESO-1b Peptide With Montanide® ISA-51 | Number of Patients With NY-ESO-1b-Specific CD8+ T Cells Measured by Tetramer Analysis | Patients with NY ESO-1 Positive Tumors | No CD8+ T cell immunity by tetramer analysis | 1 Participants |
| NY-ESO-1b Peptide With Montanide® ISA-51 | Number of Patients With NY-ESO-1b-Specific CD8+ T Cells Measured by Tetramer Analysis | Patients with NY-ESO-1 Negative Tumors | CD8+ T cell immunity by positive tetramer | 3 Participants |
| NY-ESO-1b Peptide With Montanide® ISA-51 | Number of Patients With NY-ESO-1b-Specific CD8+ T Cells Measured by Tetramer Analysis | Patients with NY-ESO-1 Negative Tumors | No CD8+ T cell immunity by tetramer analysis | 2 Participants |
Secondary
Number of Patients With NY-ESO-1b-specific Delayed-type Hypersensitivity (DTH)
NY-ESO-1b-specific delayed-type hypersensitivity (DTH) was measured by number of patients with induration and/or redness at each timepoint. NY-ESO-1b-specific DTH skin reaction was measured at baseline and weeks 7 and 16. The NY-ESO-1b peptide solution (0.1 mg/mL in 8% DMSO) was injected intradermally at a separate site from the vaccination to give a visable and palpable skin depot. The extent and intensity of DTH reactions were documented by measuring visible redness, palpable induration and other signs of local skin irritation or necrosis. Assessment of DTH reaction was performed 48 hours after injection, and the diameter of the reaction was documented.
Time frame: up to 16 weeks
Population: All patients who entered the study, received treatment and had at least 1 post-baseline DTH test.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NY-ESO-1b Peptide With Montanide® ISA-51 | Number of Patients With NY-ESO-1b-specific Delayed-type Hypersensitivity (DTH) | DTH Reaction | 0 Participants |
| NY-ESO-1b Peptide With Montanide® ISA-51 | Number of Patients With NY-ESO-1b-specific Delayed-type Hypersensitivity (DTH) | No DTH Reaction | 9 Participants |
Post Hoc
Clinical Outcome as Measured by Number of Patients With No Evidence of Disease and Number of Participants Who Progressed
Although clinical outcome was not an endpoint of this study, patients were evaluated for disease progression throughout the study by cancer antigen 125 (CA-125) levels, physical examination and at the time of study completion with CT scan. All patients enrolled in the study were confirmed to be in Complete Response (cCR) at the initiation of therapy, as documented by CA-125 at \<35 units/mL, physical examination, and CT scan without evidence of disease. Patients were assessed for disease progression by CA-125 during the study at weeks 7 and 16. CT scan was done after completion of the study (week 16). After completion of the study, patients returned to the care of their primary treating oncologist, and monitoring was at the discretion of the treating physician. No evidence of disease (NED) was defined as no consistent increase in CA-125 or evidence of new lesions on CT scans. Progression was defined as the appearance of new lesions on CT scan.
Time frame: up to 52 months
Population: All patients who entered the study and received treatment.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| NY-ESO-1b Peptide With Montanide® ISA-51 | Clinical Outcome as Measured by Number of Patients With No Evidence of Disease and Number of Participants Who Progressed | Week 16 (End of Study) | NED | 7 Participants |
| NY-ESO-1b Peptide With Montanide® ISA-51 | Clinical Outcome as Measured by Number of Patients With No Evidence of Disease and Number of Participants Who Progressed | Week 16 (End of Study) | Progression | 2 Participants |
| NY-ESO-1b Peptide With Montanide® ISA-51 | Clinical Outcome as Measured by Number of Patients With No Evidence of Disease and Number of Participants Who Progressed | Month 52 (last follow-up) | NED | 3 Participants |
| NY-ESO-1b Peptide With Montanide® ISA-51 | Clinical Outcome as Measured by Number of Patients With No Evidence of Disease and Number of Participants Who Progressed | Month 52 (last follow-up) | Progression | 6 Participants |