Renal Cell CarcinomaPhase 1NCT03200587
Cabometyx and Avelumab in Patients With Metastatic Renal Cell Carcinoma (mRCC)
A Phase 1 study testing Avelumab and Cabozantinib in people with Renal Cell Carcinoma, run by University of Utah at 1 site in United States.
Trial summary
This is an open-label, non-controlled, non-randomized, phase I dose-finding, of Cabometyx + Avelumab, to establish safety, feasibility, and the maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D) of Cabometyx in combination with Avelumab, and to investigate preliminary efficacy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- Avelumab and Cabozantinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jun 2018to 25 Nov 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Optional Pre-Screening Eligibility for Patients Scheduled for Cytoreductive Nephrectomy
- Male or female subject aged ≥ 18 years.
- Clinically, subject is a candidate for RCC diagnostic procedure (biopsy or surgery).
- Subject meets standard of care eligibility criteria for consideration of treatment with immunotherapy using a checkpoint inhibitor following surgical resection or biopsy.
- Treatment Inclusion
- Male or female subject aged ≥ 18 years.
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- Histologically proven renal cell carcinoma with a clear cell component.
- Radiographic evidence of metastatic disease.
- Measurable disease by RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) Score 0-2
- Adequate organ function as described in the protocol
- Negative serum or urine pregnancy test at screening for women of childbearing potential
- Highly effective contraception for both male and female subjects throughout the study and for at least 120 days after last Avelumab treatment administration if the risk of conception exists
- Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
Who cannot join
- Current use of immunosuppressive medication, EXCEPT for the following:
- intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
- Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent;
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
- Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent per treating physician's clinical judgment. Subjects with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
- Prior organ transplantation including allogenic stem-cell transplantation.
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- Active infection requiring intravenous antibiotics (antibiotics should have been completed prior to registration).
- Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
- Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. If the patient has a history of HBV or HCV then confirmatory polymerase chain reaction (PCR) testing is required to confirm the disease is not active.
- Live vaccinations within 4 weeks of the first dose of Avelumab and while on trial is prohibited.
- Prior exposure to checkpoint therapy or Cabozantinib.
- Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3).
- Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
- Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
- Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
- Subjects taking prohibited medications as described in protocol. A washout period of prohibited medications for a period of at least two weeks or as clinically indicated should occur prior to the start of treatment
- Pregnant women or lactating women who are breastfeeding are excluded from this study.
- Stroke (including transient ischemic attack (TIA), myocardial infarction, or other ischemic event or symptomatic pulmonary embolism (PE) less than or equal to 6 months before dose of Cabometyx.
- Subjects with a diagnosis of deep vein thrombosis (DVT) or incidentally detected asymptomatic PE on routine scans are allowed if stable and treated with therapeutic anticoagulation for at least 2 weeks before first dose.
- Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose.
Trial locations and contacts
1 site in 1 country.
United States1 site
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
Official title: A Phase 1B, Open Label, Dose-finding Study to Evaluate the Safety and Tolerability of Cabometyx and Avelumab in Patients With Metastatic Renal Cell Carcinoma (mRCC)
This is an open-label, non-controlled, non-randomized, phase I dose-finding, of Cabometyx + Avelumab, to establish safety, feasibility, and the maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D) of Cabometyx in combination with Avelumab, and to investigate preliminary efficacy. The MTD or RP2D determined in this study will be used for a future study to formally test efficacy. The MTD determined by dose escalation will be the recommended Phase 2 dose.
- Conditions
- Renal Cell Carcinoma
- Being tested
- Avelumab, Cabozantinib
- Keywords
- Metastatic
- Medical subject headings
- Carcinoma, Renal Cell, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvelumabDrug
Avelumab 10 mg/kg infusion every 2 weeks (Days 1 and 15) of every 28 day cycle for up to 12 cycles
CabozantinibDrug
Also called Cabometyx
Cabozantinib oral daily at 20 (starting dose 1), 40 (Dose Level 2) or 60 mg (Dose Level 3)
| Study group | Role | What they receive |
|---|---|---|
| Avelumab and cabozantinib, all patients | Experimental | Not described Receives: Drug: Avelumab; Drug: Cabozantinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the recommended Phase II dose
To assess the safety and tolerability of Avelumab + Cabometyx in subjects with mRCC and determine the recommended Phase II dose (RP2D). Safety, tolerability, adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs).
Measured: 1 cycle (28 days)
Secondary outcomes (1)
Progression Free Survival (PFS)
To describe the clinical activity of Avelumab + Cabometyx in subjects with mRCC
Measured: 2 years (Most patients are expected to be on treatment for approximately 10 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2017
- Study start21 Jun 2018
- Primary completion14 Apr 2020
- Study completion25 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by University of UtahThe 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
- Not applicable
- Intervention model
- Single group
- Model description
- A phase 1B, open label, dose-finding study
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- EMD Serono
- Responsible party
- Sponsor
- Investigators
- Neeraj Agarwal, MD, Principal investigator, Huntsman Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03200587
- Sponsor's protocol ID
- HCI102309
- Status last verified
- Jul 2024
- First submitted
- 23 Jun 2017
- Last updated
- 3 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Li H, Sahu KK, Brundage J, Benson M, Swami U, Boucher KM, Gupta S, Hawks J, Sirohi D, Agarwal N, Maughan BL. Phase I Trial of Combination Therapy With Avelumab and Cabozantinib in Patients With Newly Diagnosed Metastatic Clear Cell Renal Cell Carcinoma. Oncologist. 2023 Aug 3;28(8):737-e693. doi: 10.1093/oncolo/oyad019.
PubMed 36952231
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1B, Open Label, Dose-finding Study to Evaluate the Safety and Tolerability of Cabometyx and Avelumab in Patients With Metastatic Renal Cell Carcinoma (mRCC)
- ClinicalTrials.gov ID
- NCT03200587
- Acronym / sponsor ID
- HCI102309
- Conditions
- Renal Cell Carcinoma
- Keywords
- Metastatic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- EMD Serono
- Study start
- 21 Jun 2018 (actual)
- Primary completion
- 14 Apr 2020 (actual)
- Study completion
- 25 Nov 2021 (actual)
- First posted
- 27 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, non-controlled, non-randomized, phase I dose-finding, of Cabometyx + Avelumab, to establish safety, feasibility, and the maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D) of Cabometyx in combination with Avelumab, and to investigate preliminary efficacy. The MTD or RP2D determined in this study will be used for a future study to formally test efficacy. The MTD determined by dose escalation will be the recommended Phase 2 dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A phase 1B, open label, dose-finding study
| Arm | Type | Receives |
|---|---|---|
| Avelumab and cabozantinib, all patients | Experimental | Drug: Avelumab, Drug: Cabozantinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Optional Pre-Screening Eligibility for Patients Scheduled for Cytoreductive Nephrectomy
- Male or female subject aged ≥ 18 years.
- Clinically, subject is a candidate for RCC diagnostic procedure (biopsy or surgery).
- Subject meets standard of care eligibility criteria for consideration of treatment with immunotherapy using a checkpoint inhibitor following surgical resection or biopsy.
- Treatment Inclusion
Key exclusion criteria (20 listed)
- Current use of immunosuppressive medication, EXCEPT for the following:
- Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent per treating physician's clinical judgment. Subjects with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
- Prior organ transplantation including allogenic stem-cell transplantation.
- Active infection requiring intravenous antibiotics (antibiotics should have been completed prior to registration).
- Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
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 |
|---|---|---|
| AvelumabAvelumab 10 mg/kg infusion every 2 weeks (Days 1 and 15) of every 28 day cycle for up to 12 cycles | Drug | Avelumab and cabozantinib, all patients |
| CabozantinibAlso: CabometyxCabozantinib oral daily at 20 (starting dose 1), 40 (Dose Level 2) or 60 mg (Dose Level 3) | Drug | Avelumab and cabozantinib, all patients |
Primary outcome
Determine the recommended Phase II dose
Time frame: 1 cycle (28 days)
To assess the safety and tolerability of Avelumab + Cabometyx in subjects with mRCC and determine the recommended Phase II dose (RP2D). Safety, tolerability, adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs).
1 secondary outcome
Progression Free Survival (PFS)
Time frame: 2 years (Most patients are expected to be on treatment for approximately 10 months)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
- Derived from this study: PubMed 36952231Li H, Sahu KK, Brundage J, Benson M, Swami U, Boucher KM, Gupta S, Hawks J, Sirohi D, Agarwal N, Maughan BL. Phase I Trial of Combination Therapy With Avelumab and Cabozantinib in Patients With Newly Diagnosed Metastatic Clear Cell Renal Cell Carcinoma. Oncologist. 2023 Aug 3;28(8):737-e693. doi: 10.1093/oncolo/oyad019.
- Individual participant dataSharing planned: No
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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.
Neeraj Agarwal, MD principal investigator
Huntsman Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Avelumab and Cabozantinib in people with Renal Cell Carcinoma, run by University of Utah at 1 site 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 14 inclusion and 20 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 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Determine the recommended Phase II dose (time frame: 1 cycle (28 days)). 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 NCT03200587, 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 3 Jul 2024.