AzTrials
AzTrials

Metastatic Renal Cell CarcinomaPhase 2NCT02639182

A Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma

A Phase 2 study testing AGS-16C3F and Axitinib in people with Metastatic Renal Cell Carcinoma, run by Astellas Pharma Global Development, Inc. at 26 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study was to evaluate the progression free survival (PFS), based on investigator radiologic review, of AGS-16C3F compared to axitinib in subjects with metastatic renal cell carcinoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Renal Cell Carcinoma
What is being tested?
AGS-16C3F and Axitinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
133 participants
Where
26 sitesin 2 countries
Study dates
3 May 2016to 2 Oct 2020
Phase
Phase 2
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

  • Histologically confirmed diagnosis of RCC
  • Non-clear subjects must be ENPP3 positive, defined as IHC H-score ≥15
  • Has evidence of progression on or after the last regimen received:
  • Clear cell subject: must have received at least 2 prior systemic regimens, one of which is an anti-VEGF agent.
  • Non-clear cell subject: must have received at least one prior anti-VEGF regimen
  • Has measurable disease according to Response Criteria for Solid Tumors (RECIST v.1.1)
Show all 40Show fewer
  • Has Eastern Cooperative Group (ECOG) performance status of 0 or 1
  • Has archive tumor tissue from primary tumor or metastatic site (excluding bone), for which the source and availability have been confirmed.
  • If no archive tissue is available, the subject may elect to have a biopsy performed to obtain tissue.
  • Has adequate organ function including:
  • Hematopoietic function as follows:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10 9/L
  • Platelet count ≥ 100 x 10 9/L
  • Hemoglobin ≥ 9 g/dL (transfusions are allowed)
  • Renal Function as follows:
  • 1. Creatinine ≤ 1.5 x upper limit of normal (ULN), or calculated glomerular filtration rate (GFR) > 40 mL/min (Cockcroft-Gault) if creatinine > 1.5x ULN
  • Hepatic function, as follows:
  • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN or ≤ 5x ULN if known liver metastases
  • Total bilirubin ≤ 1.5 x ULN
  • Prothrombin time (PT) and activated partial thromboplastin time (aPTT) levels ≤1.5 x ULN. If institution does not report PT value, the international normalization ratio (INR) must be ≤ ULN.
  • If subject is receiving Coumadin (warfarin), a stable international normalization ratio (INR) of 2-3 is required.
  • No clinical symptoms of hypothyroidism
  • Urine Protein to Creatinine Ratio (uPCR) < 2.0
  • If uPCR ≥ 2.0 then a 24-hour urine collection can be performed to qualify. If this is performed to qualify, the protein result must be < 2 g per 24 hours.
  • Female subject must either:
  • Be of non-childbearing potential:
  • post-menopausal (defined as at least 1 year without any menses) prior to Screening, or
  • documented surgically sterile
  • Or, if of childbearing potential,
  • Agree not to try to become pregnant during the study and for 6 months after the final study drug administration
  • And have a negative serum pregnancy test ≤ 10 days of cycle 1, day 1 (C1D1)
  • And, if heterosexually active, agree to consistently use 2 forms of highly effective birth control* (at least one of which must be a barrier method) starting at Screening and throughout the study period and for 6 months after the final study drug administration.
  • Female subject must agree not to breastfeed starting at Screening and throughout the study period, and for 6 months after the final study drug administration.
  • Female subject must not donate ova starting at Screening and throughout the study period, and for 6 months after the final study drug administration.
  • Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception* consisting of 2 forms of birth control (at least one of which must be a barrier method) starting at Screening and continue throughout the study period, and for 6 months after the final study drug administration
  • Male subject must not donate sperm starting at Screening and throughout the study period and, for 6 months after the final study drug administration
  • Note: Highly effective forms of birth control include:
  • Consistent and correct usage of established oral contraception.
  • Established intrauterine device (IUD) or intrauterine system (IUS).
  • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository

Who cannot join

  • Has previously been treated with axitinib, AGS-16C3F, or AGS-16M8F
  • Has untreated brain metastasis. In the case of a solitary brain metastasis which has been resected, there must be evidence of a disease-free interval of at least 3 months post-surgery. For brain metastases treated with whole brain or stereotactic radiation therapy, brain imaging must be stable > 3 months. All subjects previously treated for brain metastases must be stable off corticosteroid therapy for at least 28 days prior to C1D1.
  • Has uncontrolled hypertension defined as blood pressure > 150/90 on medication(s) by 2 blood pressure readings taken at least 1 hour apart.
  • Has gastrointestinal abnormalities including:
  • inability to take oral medication;
  • requirement for intravenous alimentation;
Show all 33Show fewer
  • prior surgical procedures affecting absorption including total gastric resection;
  • active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy;
  • malabsorption syndromes such as celiac disease, cystic fibrosis, inflammatory bowel disease, systemic sclerosis, and carcinoid syndrome
  • Has ocular conditions such as:
  • Active infection or corneal ulcer
  • Monocularity
  • Visual acuity of 20/70 or worse in both eyes
  • History of corneal transplantation
  • Contact lens dependent (if using contact lens, must be able to switch to glasses during the entire study duration)
  • Uncontrolled glaucoma (topical medications allowed)
  • Uncontrolled or active ocular problems (e.g., retinopathy, macular edema, active uveitis, wet macular degeneration) requiring surgery, laser treatment, or intravitreal injections
  • Papilledema or other active optic nerve disorder
  • Has used any investigational drug (including marketed drugs not approved for this indication) ≤ 14 days of C1D1. No time limit applies to the use of marketed drugs approved for this indication provided that the subject has progressed on the treatment and all toxicities attributable to the drug have resolved, returned to baseline or stabilized.
  • Has known sensitivity to any of the ingredients of:
  • investigational product AGS-16C3F and/or,
  • Inlyta® (axitinib) and/or,
  • 1% prednisolone acetate ophthalmic suspension and any other corticosteroids.
  • Is currently using (i.e., within 14-days prior to first dose) drugs that are known strong CYP3A4/5 inhibitors / inducers.
  • Thromboembolic event (e.g., deep vein thrombosis [DVT] and pulmonary embolism [PE]) ≤ 4 weeks of C1D1.
  • Subjects who had a thromboembolic event ≤ 4 weeks of C1D1 must be receiving adequate anticoagulation treatment for at least 2 weeks before C1D1 and must continue as clinically indicated post first dose
  • Has history bleeding disorders (e.g., pulmonary hemorrhage, significant hemoptysis, menometrorrhagia not responding to hormonal treatment) ≤ 2 months before C1D1
  • Has active angina or Class III or IV Congestive Heart Failure (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 6 months of randomization, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, congestive heart failure, or arrhythmias not controlled by medication.
  • Had major surgery ≤ 4 weeks of C1D1
  • Is pregnant (confirmed by positive serum pregnancy test) or lactating
  • Has active infection requiring treatment with systemic (intravenous or oral) anti-infectives (antibiotic, antifungal, or antiviral agent) ≤ 10 days of C1D1
  • Is unwilling or unable to comply with study requirements
  • Has any medical or psychiatric disorder that compromises the ability of the subject to give written informed consent, and/or comply with the study procedures.

Trial locations and contacts

26 sites in 2 countries.

26 sites in 2 countries

United States20 sites

  • Site US01004

    Ann Arbor, Michigan, 48109

  • Site US01010

    Atlanta, Georgia, 30322

  • Site US01023

    Baltimore, Maryland, 21201

  • Site US01002

    Boston, Massachusetts, 02215

  • Site US01006

    Buffalo, New York, 14263

  • Site US01011

    Charleston, South Carolina, 29425

  • Site US01013

    Detroit, Michigan, 48202

  • Site US01022

    Durham, North Carolina, 27710

  • Site US01003

    Houston, Texas, 77030

  • Site US01008

    La Jolla, California, 92093

  • Site US01007

    Los Angeles, California, 90033

  • Site US01020

    Los Angeles, California, 90095

  • Site US01009

    Milwaukee, Wisconsin, 53226

  • Site US01012

    Omaha, Nebraska, 68130

  • Site US01019

    Palo Alto, California, 94305

  • Site US01021

    Pittsburgh, Pennsylvania, 15232

  • Site US01017

    Portland, Oregon, 97213

  • Site US01001

    Seattle, Washington, 98109

  • Site US01014

    Temple, Texas, 76508

  • Site US01026

    Tucson, Arizona, 85719

Other trials in United States

Canada6 sites

  • Site CA02006

    Calgary, Alberta, T2N 4N2

  • Site CA02004

    Edmonton, Alberta, T6G 1Z2

  • Site CA02002

    Hamilton, Ontario, L8V 5C2

  • Site CA02005

    Kelowna, British Columbia, V1Y 5L3

  • Site CA02008

    London, Ontario, N6A 5W9

  • Site CA02001

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

About this study

Official title: A Multi-Center, Open Label, Randomized Phase 2 Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma

The purpose of this study was to evaluate the progression free survival (PFS), based on investigator radiologic review, of AGS-16C3F compared to axitinib in subjects with metastatic renal cell carcinoma.

Being tested
AGS-16C3F, Axitinib
Keywords
Axitinib, Metastatic Renal Cell Carcinoma, AGS-16C3F
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AGS-16C3FDrug

    Intravenous (IV) infusion

  • AxitinibDrug

    Also called Inlyta®

    Oral

Study groups in NCT02639182
Study groupRoleWhat they receive
AGS-16C3FExperimentalParticipants received 1.8 milligram per kilogram (mg/kg) of AGS-16C3F once every three weeks by single intravenous (IV) infusion.
Receives: Drug: AGS-16C3F
AxitinibActive comparatorParticipants received 2 to 10 milligram (mg) of axitinib twice daily by oral administration as defined in the product label and per local institutional guidelines.
Receives: Drug: Axitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigator Radiologic Review

    PFS was defined as the time from the date of randomization to the earliest of documented disease progression as defined by RECIST v.1.1 or death from any cause. PFS was analysed using Kaplan-Meier estimates. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters (longest for non-nodal lesions, short axis for nodal lesions) of the target lesions taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of 1 or more new lesions is also considered progression. Participants were censored if there were 2 or more than 2 consecutive missing assesments immediately prior to death or progression; or no death and no postebaseline assesments; or if ininitiated non protocol anticancer treatment prior to death or prior to documentation of disease progression; or alive and not progressed.

    Measured: From date of randomization to the earliest of either documented disease progression or death from any cause (up to 53 months)

Secondary outcomes (21)

  1. PFS Per RECIST v1.1 as Assessed by Blinded Central Radiology Assessment

    PFS was defined as the time from the date of randomization to the earliest of documented disease progression as defined by RECIST v.1.1 or death from any cause. PFS was analysed using Kaplan-Meier estimates. PD was defined as at least a 20% increase in the sum of diameters (longest for non-nodal lesions, short axis for nodal lesions) of the target lesions taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. The appearance of 1 or more new lesions is also considered progression. Participants were censored if there were 2 or more than 2 consecutive missing assessments immediately prior to death or progression; or no death and no postebaseline assessments; or if initiated non protocol anticancer treatment prior to death or prior to documentation of disease progression; or alive and not progressed.

    Measured: From date of randomization to the earliest of either documented disease progression or death from any cause (up to 40 months)

  2. Objective Response Rate (ORR) Based on the Investigator's Radiographic Assessment

    ORR was defined as the percentage of participants who had a best overall response of complete response (CR) or partial response (PR). CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) with reduction in short axis to <10mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.

    Measured: From date of randomization until data cutoff date of 21 August 2019 (up to 40 months)

  3. Duration of Response (DOR) Based on the Investigator's Radiographic Assessment

    DOR was defined as the time from the date of the first response of CR or PR (whichever was first recorded) to the first date of documented PD or death due to any cause. DOR was analysed using Kaplan-Meier estimates. CR and PR were defined in outcome measure 3 and PD was defined in outcome measures 1 and 2. Participants were censored if there were 2 or more than 2 consecutive missing assesments immediately prior to death or progression; or no death and no postebaseline assesments; or if ininitiated non protocol anticancer treatment prior to death or prior to documentation of disease progression; or alive and not progressed.

    Measured: From date of first objective response until data cutoff date of 21 August 2019 (up to 40 months)

  4. Overall Survival (OS)

    OS was defined as the time from the date of randomization until the date of death from any cause. OS was analysed using Kaplan-Meier estimates. Participants were censored if there was no death and no postbaseline contact or no death and at least one postbaseline follow-up.

    Measured: Date of randomization until the date of death from any cause (up to 53 months)

  5. Disease Control Rate (DCR) Based on the Investigator's Radiographic Assessment

    DCR was defined as the percentage of patients who had a best overall response of CR, PR or at least 6 months with stable disease (SD). CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) with reduction in short axis to <10mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. SD was defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference the smallest sum of diameters while on study drug.

    Measured: Date of randomization until data cutoff date of 21 August 2019 (up to 40 months)

  6. Number of Participants With Adverse Events

    AE was defined as any untoward medical occurrence in a participant administered a study drug or has undergone study procedures and which did not necessarily have a causal relationship with this treatment. An abnormality identified during a medical test (e.g., laboratory parameter, vital sign, ECG data, and physical exam) was defined as an AE only if the abnormality induces clinical signs or symptoms or requires active intervention or requires interruption or discontinuation of study medication or the abnormality or investigational value is clinically significant in the opinion of the investigator. AE was considered "serious" if it results in death or is life threatening results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions or results in congenital anomaly, or birth defect requires inpatient hospitalization or leads to prolongation of hospitalization or other medically important events.

    Measured: From first dose up to 53 months

  7. Maximum Observed Serum Concentration (Cmax) of Antibody Drug Conjugate (ADC)

    Cmax of ADC was reported.

    Measured: Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

  8. Mean Predose Serum Concentration (Ctrough) of ADC

    Ctrough of ADC was reported.

    Measured: Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)

  9. Time to Maximum Observed Serum Concentration (Tmax) of ADC

    Tmax of ADC was reported.

    Measured: Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

  10. Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of ADC

    AUC (0 to 21) of ADC was reported.

    Measured: Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

  11. Terminal Elimination Half-life (t1/2) of ADC

    t1/2 of ADC was reported.

    Measured: Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

  12. Maximum Serum Concentration (Cmax) of Total Antibody (TAb)

    Cmax of TAb was reported.

    Measured: Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

  13. Mean Predose Serum Concnetration (Ctrough) of TAb

    Ctrough of TAb was reported.

    Measured: Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)

  14. Time to Maximum Observed Serum Concentration (Tmax) of Tab

    Tmax of TAb was reported.

    Measured: Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

  15. Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of TAb

    AUC (0 to 21) of TAb was reporetd.

    Measured: Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

  16. Terminal Elimination Half-life (t1/2) of Tab

    t1/2 of TAb was reported.

    Measured: Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

  17. Maximum Serum Concentration (Cmax) of Cysteine Adduct of Maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF)

    Cmax of Cys-mcMMAF was reported.

    Measured: Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

  18. Mean Predose Serum Concnetration (Ctrough) of Cys-mcMMAF

    Ctrough of Cys-mcMMAF was reported.

    Measured: Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)

  19. Time to Maximum Observed Serum Concentration (Tmax) of Cys-mcMMAF

    Tmax of Cys-mcMMAF was reported.

    Measured: Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

  20. Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of Cys-mcMMAF

    AUC (0 to 21) of Cys-mcMMAF was reporetd.

    Measured: Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

  21. Terminal Elimination Half-life (t1/2) of Cys-mcMMAF

    t1/2 of Cys-mcMMAF was reported

    Measured: Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Dec 2015 (estimated)
  2. Study start3 May 2016
  3. Primary completion2 Oct 2020
  4. Study completion2 Oct 2020

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
133 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02639182
Sponsor's protocol ID
AGS-16C3F-15-3
Status last verified
Oct 2024
First submitted
21 Dec 2015
Last updated
18 Nov 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AGS-16C3F and Axitinib in people with Metastatic Renal Cell Carcinoma, run by Astellas Pharma Global Development, Inc. at 26 sites in 2 countries.

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 40 inclusion and 33 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 18 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States, Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 23 Sep 2020). 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?

Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigator Radiologic Review (time frame: From date of randomization to the earliest of either documented disease progression or death from any cause (up to 53 months)). 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 NCT02639182.

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 18 Nov 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in