Cervical Cancer
Conditions
Keywords
cervical cancer, Stage IB, Stage IIA, Stage IIB, Stage IIIA, Stage IIIB, Stage IVA
Brief summary
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of the investigational drug in combination with radiation to learn whether the drug(s) works in treating a specific disease. In this study, researchers are studying three treatment arms, each using standard chemotherapy, with the drug cisplatin and radiation and the drug Nivolumab. Each treatment Arm will test the addition of Nivolumab at a different time point
Interventions
DRUGNivolumab induction
2 doses Nivolumab 240mg IV
DRUGCisplatin
40 mg/m2 of cisplatin: Dosing on Days: 1, 8, 15, 22, 29, 36 beginning on day 1 of radiation therapy.
RADIATIONRadiation
Total dose of 45 Gy in 25 fractions at 180 cGy/fx Whole pelvic or extended field
DRUGNivolumab with chemoradiation
Nivolumab 240mg IV every 14 days (+/- 3 days) for 3 doses, administered concomitantly during chemoradiation and beginning day 1 of Radiation.
DRUGNivolumab maintenance
Nivolumab 480 mg IV every 4 weeks for 2 years
Sponsors
Rhode Island Hospital
The Miriam Hospital
Women and Infants Hospital of Rhode Island
Bristol-Myers Squibb
Brown University
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
* Age ≥ 18 years. * ECOG performance status ≤2 * Patients with histologically confirmed advanced cervical cancer (any cell type): FIGO Clinical stages IB, IIA, IIB, IIIA, IIIB, IVA. * Participants must have normal organ and marrow function as defined below: 1. absolute neutrophil count ≥1,500/mcL 2. platelets ≥100,000/mcL 3. total bilirubin within normal institutional limits 4. AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal 5. creatinine Within normal institutional limits * Neuropathy (sensory and motor) ≤ CTCAE v4.0 grade 1 * Patients with ureteral obstruction should undergo stent or nephrostomy tube placement prior to study entry. Any side effects or complications associated with stent placement that, in the opinion of the treating investigator, puts the patient at increased risk for treatment-related toxicity, must be resolved completely prior to study enrollment. * Patients of child-bearing potential must have a negative serum pregnancy test prior to study entry (within 7 days prior to initiation of study treatment) and be practicing an effective form of contraception during study treatment and for 24 months (2 years) thereafter. * Women should not breast-feed while on this study * Patients must not be receiving any other investigational agent * Ability to understand and the willingness to sign a written informed consent document. * All patients with a history of hearing loss are required to have an audiogram within 28 days prior to initiating protocol therapy. If patient does not have a history of hearing loss this must be documented by treating physician.
Exclusion criteria
* Participants with visceral metastases, including brain metastases. * Uncontrolled intercurrent illness * Patients who have received previous pelvic or abdominal radiation, cytotoxic chemotherapy, or previous therapy of any kind for this malignancy * Patients who have circumstances that will not permit completion of this study or the required follow-up as per the treating physician * Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer are excluded if there is any evidence of other malignancy being present within the last three years (2 years for invasive breast cancer). However, patients with a malignancy that is non-likely to require treatment, as per the treating physician, in the next 2 years, such as a completely resected, early stage breast cancer, are eligible. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy. * Prior treatment with immunotherapy for any cancer, including immune checkpoint inhibitors or anti-CTLA4 agents * Patients with renal abnormalities, such as pelvic kidney, horseshoe kidney, or renal transplantation, that would require modification of radiation fields as documented by treating physician
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | From start of study treatment through date of study completion, an average of 2 years. | Number of patients that are alive without disease progression at time of analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence Patterns | From start of study treatment through date of study completion, an average of 2 years. | Determination of the site of recurrence, loco-regional versus distant |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1A Nivolumab during Chemo/RT with whole pelvic RT
Nivolumab induction: 2 doses Nivolumab 240mg IV
Cisplatin: 40 mg/m2 of cisplatin: Dosing on Days: 1, 8, 15, 22, 29, 36 beginning on day 1 of radiation therapy.
Radiation: Total dose of 45 Gy in 25 fractions at 180 cGy/fx
Whole pelvic or extended field
Nivolumab with chemoradiation: Nivolumab 240mg IV every 14 days (+/- 3 days) for 3 doses, administered concomitantly during chemoradiation and beginning day 1 of Radiation. | 3 |
| Cohort 1B Nivolumab during Chemo/RT with extended field
Nivolumab induction: 2 doses Nivolumab 240mg IV
Cisplatin: 40 mg/m2 of cisplatin: Dosing on Days: 1, 8, 15, 22, 29, 36 beginning on day 1 of radiation therapy.
Radiation: Total dose of 45 Gy in 25 fractions at 180 cGy/fx
Whole pelvic or extended field
Nivolumab with chemoradiation: Nivolumab 240mg IV every 14 days (+/- 3 days) for 3 doses, administered concomitantly during chemoradiation and beginning day 1 of Radiation. | 1 |
| Cohort 2 Chemoradiation followed by Nivolumab Maintenance
Nivolumab induction: 2 doses Nivolumab 240mg IV
Cisplatin: 40 mg/m2 of cisplatin: Dosing on Days: 1, 8, 15, 22, 29, 36 beginning on day 1 of radiation therapy.
Radiation: Total dose of 45 Gy in 25 fractions at 180 cGy/fx
Whole pelvic or extended field
Nivolumab maintenance: Nivolumab 480 mg IV every 4 weeks for 2 years | 0 |
| Cohort 3 Nivolumab during chemoradiation and then as maintenance
Nivolumab induction: 2 doses Nivolumab 240mg IV
Cisplatin: 40 mg/m2 of cisplatin: Dosing on Days: 1, 8, 15, 22, 29, 36 beginning on day 1 of radiation therapy.
Radiation: Total dose of 45 Gy in 25 fractions at 180 cGy/fx
Whole pelvic or extended field
Nivolumab with chemoradiation: Nivolumab 240mg IV every 14 days (+/- 3 days) for 3 doses, administered concomitantly during chemoradiation and beginning day 1 of Radiation.
Nivolumab maintenance: Nivolumab 480 mg IV every 4 weeks for 2 years | 0 |
| Total | 4 |
Baseline characteristics
| Characteristic | Cohort 1A | Cohort 1B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Continuous | 66 years | 54 years | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment United States | 3 participants | 1 participants | 4 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 1 |
| other Total, other adverse events | 3 / 3 | 1 / 1 |
| serious Total, serious adverse events | 2 / 3 | 1 / 1 |
Outcome results
Primary
Progression Free Survival
Number of patients that are alive without disease progression at time of analysis.
Time frame: From start of study treatment through date of study completion, an average of 2 years.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1A | Progression Free Survival | 2 Participants |
| Cohort 1B | Progression Free Survival | 1 Participants |
Secondary
Recurrence Patterns
Determination of the site of recurrence, loco-regional versus distant
Time frame: From start of study treatment through date of study completion, an average of 2 years.
Population: Only 1 patient on cohort 1A had recurrence within 3 years of study entry.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1A | Recurrence Patterns | Loco-regional | 1 Participants |
| Cohort 1A | Recurrence Patterns | Distant | 0 Participants |
| Cohort 1B | Recurrence Patterns | Loco-regional | 0 Participants |
| Cohort 1B | Recurrence Patterns | Distant | 0 Participants |