Carcinoma, Non-Small-Cell LungPhase 1MDX1106-01NCT00441337
A Study of MDX-1106 in Patients With Selected Refractory or Relapsed Malignancies
A Phase 1 study testing MDX-1106 in people with Carcinoma, Non-Small-Cell Lung and Colorectal Cancer, run by Bristol-Myers Squibb at 4 sites in United States.
Trial summary
To evaluate the safety, tolerability, efficacy, and pharmacokinetics of MDX-1106 when administered to patients with advanced non-small cell lung cancer, colorectal cancer, malignant melanoma, clear cell renal cell cancer or hormone refractory prostate cancer Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung, Colorectal Cancer, Malignant Melanoma
- What is being tested?
- MDX-1106
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 4 sitesUnited States
- Study dates
- Aug 2006to Nov 2009
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Relapsed/refractory non-small cell lung cancer, colorectal adenocarcinoma, malignant melanoma, renal (clear) cell carcinoma, or hormone-refractory prostate adenocarcinoma
- Prior treatment must have been completed at least 4 weeks prior to enrollment
- No untreated primary or metastatic brain or meningeal tumors
- ECOG PS 0 or 1
- Meet all screening laboratory values
Who cannot join
- History of severe hypersensitivity reactions to other monoclonal antibodies
- Active autoimmune disease or a documented history of autoimmune disease
- Prior therapy with an anti-PD-1 or anti-CTLA-4 antibody
- Active infection
- Concurrent medical condition requiring the use of immunosuppressive medications
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Johns Hopkins Unv., School of Medicine
Baltimore, Maryland, 21231
Henry Ford Health System
Detroit, Michigan, 48202
Carolina BioOncology Institute, PLLC
Huntersville, North Carolina, 28078
Washington University School of Medicine - Barnes Jewish Hospital
St Louis, Missouri, 63110
About this study
Official title: A Phase 1, Open Label, Dose-escalation, Safety and Pharmacokinetic Study of MDX-1106 in Patients With Selected or Relapsed Malignancies
To evaluate the safety, tolerability, efficacy, and pharmacokinetics of MDX-1106 when administered to patients with advanced non-small cell lung cancer, colorectal cancer, malignant melanoma, clear cell renal cell cancer or hormone refractory prostate cancer
Read the detailed description
Six patients enrolled at each dose level of 0.3, 1.0, 3.0 and 10mg/kg; the remaining 10 to 15 patients may subsequently be enrolled at a dose at or below the maximum tolerated dose (MTD) during the dose-escalation portion of the study. Patients who respond may receive additional doses of drug.
- Conditions
- Carcinoma, Non-Small-Cell Lung, Colorectal Cancer, Malignant Melanoma, Renal Cancer, Prostate Cancer
- Being tested
- MDX-1106
- Keywords
- malignancies, cancer, non small cell lung cancer, lung cancer, colorectal cancer, adenocarcinoma, melanoma, malignant melanoma, renal cancer, renal carcinoma, carcinoma, prostate cancer, prostate adenocarcinoma, Recurrent or treatment refractory malignancies
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Melanoma, Kidney Neoplasms, Prostatic Neoplasms, Neoplasms, Lung Neoplasms, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MDX-1106Biological
Also called nivolumab
patients will receive a single dose of MDX-1106 as a 60 minute infusion.
| Study group | Role | What they receive |
|---|---|---|
| 0.3 mg/kg MDX-1106 drug | Experimental | 0.3 milligrams (mg) MDX-1106 drug (nivolumab) per kilogram (kg) of body weight (mg/kg) was administered in a single intravenous (IV) infusion. If criteria were met, 2 additional doses could be administered (1 every 4 weeks). Receives: Biological: MDX-1106 |
| 1 mg/kg MDX-1106 drug | Experimental | 1 mg MDX-1106 drug (nivolumab) per kg of body weight (mg/kg) was administered in a single IV infusion. If criteria were met, 2 additional doses could be administered (1 every 4 weeks). Receives: Biological: MDX-1106 |
| 3 mg/kg MDX-1106 drug | Experimental | 3 mgs MDX-1106 drug (nivolumab) per kg of body weight (mg/kg) was administered in a single IV infusion. If criteria were met, 2 additional doses could be administered (1 every 4 weeks). Receives: Biological: MDX-1106 |
| 10 mg/kg MDX-1106 drug | Experimental | 10 mgs MDX-1106 drug (nivolumab) per kg of body weight (mg/kg) was administered in a single IV infusion. If criteria were met, 2 additional doses could be administered (1 every 4 weeks). Receives: Biological: MDX-1106 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Drug-Related AEs, Deaths, Discontinuation of Study Drug Due to AE, Dose-Limiting Toxicity (DLT) AE and Immune-related AEs (irAEs) in Safety Population
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Severe=All Grade 3 or 4 events. Death=during the study and up to 28 days past study discontinuation. AEs graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0. irAEs=unknown etiology, associated with study drug and consistent with an immune phenomenon. DLT: ≥Gr 3 AE(s) or lab abnormality without alternative explanation other than drug.
Measured: Day 1 to 70 days post last dose of study drug; 28 days past study discontinuation
Geometric Mean Maximum Serum Concentration (Cmax) Observed Post-Single Dose
Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated enzyme-linked immunosorbent assay (ELISA) method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The pharmacokinetic (PK) parameter of Cmax was measured in micrograms per milliliter (µg/mL).
Measured: Day 1 to Day 85
Median Time at Which the Maximum Serum Concentration Occurred (Tmax) Post-Single Dose
Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameter of Tmax was measured in hours (h).
Measured: Day 1 to Day 85
Geometric Mean Area Under the Curve (AUC) From Time of Dosing to Time of Last Observation (0-T) and Extrapolated to Infinity (INF) Observed Post-Single Dose
AUC(0-T): Area under the concentration-time curve from the time of dosing to the time of the last observation. AUC(INF): Area under the curve from the time of dosing extrapolated to infinity. Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameters of AUC(0-T) and AUC (INF) were measured in micrograms*hours per milliliter (µg*h/mL).
Measured: Day 1 to Day 85
Mean Elimination Half-life (T-HALF) Post-Single Dose
Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameter of T-HALF was measured in days.
Measured: Day 1 to Day 85
Geometric Mean Total Body Clearance of Drug From Serum (CLT) Post-Single Dose
Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameter of CLT was measured in milliliters per hour per kilogram body weight (mL/h/kg).
Measured: Day 1 to Day 85
Mean Volume of Distribution (Vz) Post-Single Dose
Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameter of Vz was measured in milliliters per kilogram of body weight (mL/kg).
Measured: Day 1 to Day 85
Percent of Participants With Best Overall Response Rate in Safety Population and in Tumor Evaluable Population
The Best Overall Response Rate (BORR) was defined as the number of participants who had a confirmed complete response (CR) or partial response (PR) during the study divided by the total number of participants evaluated. Response was based on tumor assessment for both target and non-target lesions using: Clinical examination; Chest X-ray; Computed Tomography and Magnetic Resonance Imaging; Bone scan; Ultrasound. Per National Cancer Institute Response Evaluation Criteria in Solid Tumors (RECIST) v1.0, best overall response (BOR) for tumors was confirmed CR or PR. CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter. Confidence intervals (CIs) were computed using the Clopper and Pearson method.
Measured: Day 1 up to 2 Years.
Percent of Participants With Prostate-Specific Antigen (PSA) Response After the First Dose by Day 85 In Participants With Hormone-Refractory Prostate Adenocarcinoma (HRPC)
The PSA response rate was defined as the number of participants who had at least a 50% decrease of the PSA value from the PSA reference value divided by the total number of participants evaluated (percent of participants). PSA reference value was the PSA concentration measured immediately prior to dosing on Day 1. PSA response was assessed using the Recommendations from the National Cancer Institute Prostate-Specific Antigen Working Group. A PSA response had to be confirmed at least 4 weeks after first response. 95% exact CIs were computed using the Clopper and Pearson method.
Measured: Day 1 to Day 85
Secondary outcomes (11)
Number of Participants With Best Overall Response (BOR) by Category in Safety Population
Measurable and non-measurable disease/target lesions were evaluated according to National Cancer Institute standardized RECIST.Complete Response (CR)=disappearance of all target and non-target lesions and no new lesions; Partial Response=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter; Stable disease (SD)=neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since treatment; PD=at least a 20% increase in the sum of the longest diameter recorded since screening, or the appearance of one or more new lesions. BOR was recorded between the first tumor assessment and last tumor assessment. CR and PR had to be confirmed by repeat assessment no less than 4 weeks after the criteria were first met. SD assessment must have met the criteria at least once at or after Week 12.
Measured: Day 1 to Day 85
Percentage of Participants With Disease Control and Major Durable Disease Control
Disease control rate was defined as number of participants whose Best Overall Response (BOR) was complete response (CR), partial response (PR), or stable disease (SD) divided by the total number of participants. Major durable disease control rate was defined as the total number of participants whose BOR was CR, PR, or SD ≥24 weeks, divided by the total number of participants. Per RECIST v 1.0, BOR for tumors was confirmed CR or PR. CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter since treatment; SD=neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for PD. PD=at least a 20% increase in the sum of the longest diameter recorded since screening, or the appearance of one or more new lesions. 95% CIs were computed using the Clopper and Pearson method.
Measured: Day 1 to 2 Years
Median Time to Tumor Response and Duration of Tumor Response
Time to tumor response: from the date of first dose to the first date of tumor response (CR or PR confirmed at least 4 weeks later); for nonresponders, it was censored at the date of the maximum tumor assessment time in the dose cohort by the end of study. Duration of tumor response was calculated from the first date of response of CR or PR to the date of the first PD or the date of death if a participant died due to disease progression (whichever occurred first). Duration of response was censored at the last tumor assessment date by the end of study if a responder did not have PD or death. Nonresponders had the duration of response as an event of 0 days.
Measured: Day 1 to 2 Years
Time to Tumor Progression and Tumor Progression Free Survival
Time to tumor progression (TTP) was measured in days from date of the first dose to the date of the first PD or the date of death if due to PD. For those who died without PD it was censored at the date of death. TTP was censored at the last tumor assessment by the end of study if a participant did not have PD or death. Tumor progression free survival (PFS) was measured in days from the date of first dose to the date of the first disease progression or to the date of death. PFS was censored at the last tumor assessment date by the end of study if a participant did not have PD or death.
Measured: Day 1 to 2 Years
Median Time to PSA Progression in Days and Median PSA Progression Free Survival in Days in PSA Evaluable Population
Time to PSA progression: first dose to first PSA progression. Missing date of progression was censored: if death during the study, time to progression was right-censored at last PSA assessment; if no progression from first dose and still alive at end of study, time to progression was right-censored at last PSA assessment by end of study; if no PSA progression and one has discontinued from the study (other than death or PSA progression), time to progression was right-censored at last PSA assessment. PSA progression free survival (PFS): first dose to first PSA progression or death, whichever comes first. Missing date of progression was censored: if one did not have PSA progression from first dose and was still alive at end of study, PSA PFS was right-censored at last PSA assessment; if one does not have any progression and discontinued from the study for reasons other than death or progression, PFS was right-censored at last assessment. CI computed using Brookmeyer and Crowley method.
Measured: Day 1 to 2 Years
Mean Change From Baseline in PSA Relative Velocity at Days 29, 57, and 85 With Cycle 1 in PSA Evaluable Population
PSA relative velocity (PSA RV) was defined as = (d[PSA]/dt)/ [PSA], where [PSA] =concentration of PSA, and t= time, and in the limit reflects the instantaneous change in PSA levels as a fraction of total PSA level. Decreases in PSA RV may occur while measured [PSA] is still rising, and may indicate that continued therapy may lead to a treatment benefit, particularly in the setting of immunotherapy, where expansion of an effective immune response is likely to require weeks to mature. Baseline PSA RV was based on the velocity of last PSA measurement before the first infusion of study drug and the screening PSA measurement.
Measured: Day 29, Day 57, Day 85
Mean Change From Baseline in Electrocardiogram Parameters PR, QRS and QT in Safety Population
12-lead ECGs were performed at screening, baseline, Day 2 and at completion of the dose cycle (Day 85 in first dose cycle). In those participants undergoing re-treatment, ECG was repeated at the completion of the re-treatment. Baseline was defined as the last measurement before the first dose of study drug, which was calculated from pre-dose or from screening if pre-dose was not available. PR, QRS and QT interval were measured in milliseconds (msec).
Measured: Baseline, Day 2, Day 85, Day 113
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population
Diastolic blood pressures (DBPs) measured in millimeters of mercury (mmHg) were obtained while the participant was seated. Post infusion DBPs are presented in the 0.3 mg cohort at: 21, 36, 51, 66, 82, 97, 112, 127, 157 minutes post infusion, and at 1, 2, 3, 4, 6, 8 hours post infusion. Baseline was defined as the last measurement before the first dose of study drug, which was calculated from pre-dose or from screening if pre-dose was not available. Mean DBP on Day 1 for first dose (cycle 1) are presented below.
Measured: Baseline, Day 1
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population
Systolic blood pressures (SBPs) measured in millimeters of mercury (mmHg) were obtained while the participant was seated. Baseline, Infusion (0 minutes) and Post infusion SBPs are presented in the 0.3 mg cohort at: 21, 36, 51, 66, 82, 97, 112, 127, 157 minutes post infusion, and at 1, 2, 3, 4, 6, 8 hours post infusion. Baseline was defined as the last measurement before the first dose of study drug, which was calculated from pre-dose or from screening if pre-dose was not available. Mean SBP on Day 1 for first dose (cycle 1) are presented below.
Measured: Baseline, Day 1
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population
Diastolic blood pressures (DBPs) measured in millimeters of mercury (mmHg) were obtained while the participant was seated. Baseline, Infusion (0 minutes) and Post infusion DBPs are presented in the 1 mg, 3 mg and 10 mg cohorts at: 15, 30, 45, 60, 75, and 90 minutes post infusion and at 1, 2, 3, 4, 6, 8 hours post infusion. Baseline was defined as the last measurement before the first dose of study drug, which was calculated from pre-dose or from screening if pre-dose was not available. Mean DBP on Day 1 for first dose (cycle 1) are presented below.
Measured: Baseline, Day 1
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population
Systolic blood pressures (SBPs) measured in millimeters of mercury (mmHg) were obtained while the participant was seated. Baseline, Infusion (0 minutes) and Post infusion SBPs are presented in the 1 mg, 3 mg and 10 mg cohorts at: 15, 30, 45, 60, 75, and 90 minutes post infusion and at 1, 2, 3, 4, 6, 8 hours post infusion. Baseline was defined as the last measurement before the first dose of study drug, which was calculated from pre-dose or from screening if pre-dose was not available. Mean SBPs on Day 1 for first dose (cycle 1) are presented below.
Measured: Baseline, Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2007 (estimated)
- Study startAug 2006
- Primary completionNov 2009
- Study completionNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00441337
- Sponsor's protocol ID
- CA209-001 ST
- Other IDs
- MDX1106-01
- Acronym
- MDX1106-01
- Status last verified
- Feb 2015
- First submitted
- 27 Feb 2007
- Last updated
- 20 Feb 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
George S, Pili R, Carducci MA, Kim JJ. Role of immunotherapy for renal cell cancer in 2011. J Natl Compr Canc Netw. 2011 Sep 1;9(9):1011-8. doi: 10.6004/jnccn.2011.0085.
PubMed 21917625
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open Label, Dose-escalation, Safety and Pharmacokinetic Study of MDX-1106 in Patients With Selected or Relapsed Malignancies
- ClinicalTrials.gov ID
- NCT00441337
- Acronym / sponsor ID
- MDX1106-01 / CA209-001 ST
- Conditions
- Carcinoma, Non-Small-Cell Lung, Colorectal Cancer, Malignant Melanoma, Renal Cancer, Prostate Cancer
- Keywords
- malignancies, cancer, non small cell lung cancer, lung cancer, colorectal cancer, adenocarcinoma, melanoma, malignant melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Aug 2006
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 28 Feb 2007 (estimated)
- Results
- Posted 20 Feb 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the safety, tolerability, efficacy, and pharmacokinetics of MDX-1106 when administered to patients with advanced non-small cell lung cancer, colorectal cancer, malignant melanoma, clear cell renal cell cancer or hormone refractory prostate cancer
Detailed description
Six patients enrolled at each dose level of 0.3, 1.0, 3.0 and 10mg/kg; the remaining 10 to 15 patients may subsequently be enrolled at a dose at or below the maximum tolerated dose (MTD) during the dose-escalation portion of the study. Patients who respond may receive additional doses of drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 0.3 mg/kg MDX-1106 drug | Experimental | Biological: MDX-11060.3 milligrams (mg) MDX-1106 drug (nivolumab) per kilogram (kg) of body weight (mg/kg) was administered in a single intravenous (IV) infusion. If criteria were met, 2 additional doses could be administered (1 every 4 weeks). |
| 1 mg/kg MDX-1106 drug | Experimental | Biological: MDX-11061 mg MDX-1106 drug (nivolumab) per kg of body weight (mg/kg) was administered in a single IV infusion. If criteria were met, 2 additional doses could be administered (1 every 4 weeks). |
| 3 mg/kg MDX-1106 drug | Experimental | Biological: MDX-11063 mgs MDX-1106 drug (nivolumab) per kg of body weight (mg/kg) was administered in a single IV infusion. If criteria were met, 2 additional doses could be administered (1 every 4 weeks). |
| 10 mg/kg MDX-1106 drug | Experimental | Biological: MDX-110610 mgs MDX-1106 drug (nivolumab) per kg of body weight (mg/kg) was administered in a single IV infusion. If criteria were met, 2 additional doses could be administered (1 every 4 weeks). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Relapsed/refractory non-small cell lung cancer, colorectal adenocarcinoma, malignant melanoma, renal (clear) cell carcinoma, or hormone-refractory prostate adenocarcinoma
- Prior treatment must have been completed at least 4 weeks prior to enrollment
- No untreated primary or metastatic brain or meningeal tumors
- ECOG PS 0 or 1
- Meet all screening laboratory values
Key exclusion criteria (5 listed)
- History of severe hypersensitivity reactions to other monoclonal antibodies
- Active autoimmune disease or a documented history of autoimmune disease
- Prior therapy with an anti-PD-1 or anti-CTLA-4 antibody
- Active infection
- Concurrent medical condition requiring the use of immunosuppressive medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MDX-1106Also: nivolumabpatients will receive a single dose of MDX-1106 as a 60 minute infusion. | Biological | 0.3 mg/kg MDX-1106 drug, 1 mg/kg MDX-1106 drug, 10 mg/kg MDX-1106 drug, 3 mg/kg MDX-1106 drug |
Primary outcome
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Drug-Related AEs, Deaths, Discontinuation of Study Drug Due to AE, Dose-Limiting Toxicity (DLT) AE and Immune-related AEs (irAEs) in Safety Population
Time frame: Day 1 to 70 days post last dose of study drug; 28 days past study discontinuation
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Severe=All Grade 3 or 4 events. Death=during the study and up to 28 days past study discontinuation. AEs graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0. irAEs=unknown etiology, associated with study drug and consistent with an immune phenomenon. DLT: ≥Gr 3 AE(s) or lab abnormality without alternative explanation other than drug.
Geometric Mean Maximum Serum Concentration (Cmax) Observed Post-Single Dose
Time frame: Day 1 to Day 85
Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated enzyme-linked immunosorbent assay (ELISA) method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The pharmacokinetic (PK) parameter of Cmax was measured in micrograms per milliliter (µg/mL).
Median Time at Which the Maximum Serum Concentration Occurred (Tmax) Post-Single Dose
Time frame: Day 1 to Day 85
Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameter of Tmax was measured in hours (h).
Geometric Mean Area Under the Curve (AUC) From Time of Dosing to Time of Last Observation (0-T) and Extrapolated to Infinity (INF) Observed Post-Single Dose
Time frame: Day 1 to Day 85
AUC(0-T): Area under the concentration-time curve from the time of dosing to the time of the last observation. AUC(INF): Area under the curve from the time of dosing extrapolated to infinity. Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameters of AUC(0-T) and AUC (INF) were measured in micrograms*hours per milliliter (µg*h/mL).
Mean Elimination Half-life (T-HALF) Post-Single Dose
Time frame: Day 1 to Day 85
Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameter of T-HALF was measured in days.
Geometric Mean Total Body Clearance of Drug From Serum (CLT) Post-Single Dose
Time frame: Day 1 to Day 85
Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameter of CLT was measured in milliliters per hour per kilogram body weight (mL/h/kg).
Mean Volume of Distribution (Vz) Post-Single Dose
Time frame: Day 1 to Day 85
Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameter of Vz was measured in milliliters per kilogram of body weight (mL/kg).
Percent of Participants With Best Overall Response Rate in Safety Population and in Tumor Evaluable Population
Time frame: Day 1 up to 2 Years.
The Best Overall Response Rate (BORR) was defined as the number of participants who had a confirmed complete response (CR) or partial response (PR) during the study divided by the total number of participants evaluated. Response was based on tumor assessment for both target and non-target lesions using: Clinical examination; Chest X-ray; Computed Tomography and Magnetic Resonance Imaging; Bone scan; Ultrasound. Per National Cancer Institute Response Evaluation Criteria in Solid Tumors (RECIST) v1.0, best overall response (BOR) for tumors was confirmed CR or PR. CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter. Confidence intervals (CIs) were computed using the Clopper and Pearson method.
Percent of Participants With Prostate-Specific Antigen (PSA) Response After the First Dose by Day 85 In Participants With Hormone-Refractory Prostate Adenocarcinoma (HRPC)
Time frame: Day 1 to Day 85
The PSA response rate was defined as the number of participants who had at least a 50% decrease of the PSA value from the PSA reference value divided by the total number of participants evaluated (percent of participants). PSA reference value was the PSA concentration measured immediately prior to dosing on Day 1. PSA response was assessed using the Recommendations from the National Cancer Institute Prostate-Specific Antigen Working Group. A PSA response had to be confirmed at least 4 weeks after first response. 95% exact CIs were computed using the Clopper and Pearson method.
11 secondary outcomes
Number of Participants With Best Overall Response (BOR) by Category in Safety Population
Time frame: Day 1 to Day 85
Percentage of Participants With Disease Control and Major Durable Disease Control
Time frame: Day 1 to 2 Years
Median Time to Tumor Response and Duration of Tumor Response
Time frame: Day 1 to 2 Years
Time to Tumor Progression and Tumor Progression Free Survival
Time frame: Day 1 to 2 Years
Median Time to PSA Progression in Days and Median PSA Progression Free Survival in Days in PSA Evaluable Population
Time frame: Day 1 to 2 Years
Mean Change From Baseline in PSA Relative Velocity at Days 29, 57, and 85 With Cycle 1 in PSA Evaluable Population
Time frame: Day 29, Day 57, Day 85
Mean Change From Baseline in Electrocardiogram Parameters PR, QRS and QT in Safety Population
Time frame: Baseline, Day 2, Day 85, Day 113
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population
Time frame: Baseline, Day 1
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population
Time frame: Baseline, Day 1
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population
Time frame: Baseline, Day 1
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population
Time frame: Baseline, Day 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21917625George S, Pili R, Carducci MA, Kim JJ. Role of immunotherapy for renal cell cancer in 2011. J Natl Compr Canc Netw. 2011 Sep 1;9(9):1011-8. doi: 10.6004/jnccn.2011.0085.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MDX-1106 in people with Carcinoma, Non-Small-Cell Lung and Colorectal Cancer, run by Bristol-Myers Squibb at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Drug-Related AEs, Deaths, Discontinuation of Study Drug Due to AE, Dose-Limiting Toxicity (DLT) AE and Immune-related AEs (irAEs) in Safety Population (time frame: Day 1 to 70 days post last dose of study drug; 28 days past study discontinuation). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00441337, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2015.