Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

All Drugs and Chemicals

Adavosertib

Enzyme Inhibitors

Patients receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Rahul R Aggarwal

This phase II trial studies how well adavosertib works in treating patients with SETD2-deficient solid tumors that have spread to other places in the body (advanced/metastatic). Adavosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria of adavosertib (AZD1775) in advanced solid tumor malignancies other than clear cell renal cell carcinoma with evidence of pathogenic loss of SETD2 using next-generation sequencing panel.

II. To determine the objective response rate by RECIST 1.1 criteria of AZD1775 in clear cell renal cell carcinoma with evidence of loss of SETD2 using next-generation sequencing panel.

SECONDARY OBJECTIVES:

I. To determine the clinical benefit rate and duration of response of AZD1775 in SETD2-deficient tumors other than clear cell renal cell carcinoma.

II. To determine the clinical benefit rate and duration of response of AZD1775 in SETD2-deficient clear cell renal cell carcinoma subgroup.

III. To characterize the safety profile of AZD1775. IV. To determine whether H3K36me3 expression by immunohistochemical assay is associated with clinical outcomes.

OUTLINE:

Patients receive adavosertib orally (PO) once daily (QD) on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Testing AZD1775 in Advanced Solid Tumors That Have a Mutation Called SETD2

A Phase 2 Study of AZD1775 in SETD2-Deficient Advanced Solid Tumor Malignancies

Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. The median duration of response will be descriptively reported using Kaplan-Meier product limit method along with 95% confidence interval. The objective response rate between cohorts will be compared using the chi-squared test.

Will be defined as patients who experience either objective response or stable disease for \>= 6 months from start of study treatment. The clinical benefit rate across the entire study cohort will be descriptively reported along with 95% confidence interval.

The median duration of response will be descriptively reported using Kaplan-Meier product limit method along with 95% confidence interval.

Will be graded by Common Toxicity Criteria version 5.0, will be descriptively reported for the safety-evaluable population.

Will be assessed by immunohistochemistry.

The median progression-free survival for each cohort will be determined using the Kaplan-Meier product limit method and compared between cohorts using the log-rank test.

National Cancer Institute (NCI)

Antineoplastic Agents

Axitinib

Protein Kinase Inhibitors

Axitinib Starting dose: 5 mg by mouth twice each day for 12 weeks.

Starting dose: 5 mg by mouth twice each day for 12 weeks.

Jose Karam, MD

The goal of this clinical research study is to learn if axitinib can help to control kidney cancer. The safety of this drug will also be studied.

The Study Drug:

Axitinib is designed to decrease blood supply to the tumor, which may slow tumor growth.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take axitinib by mouth 2 times a day every day for 12 weeks. The dose may be changed based on any side effects you may have. You should take the drug about 12 hours apart. You should take the pills at about the same time each day. If you vomit anytime after taking a dose, you must not "make it up" with an extra dose, but instead take the next dose as previously scheduled. Any missed dose may be taken late up to 3 hours before the next scheduled dose, otherwise, it should be skipped.

A blood pressure monitor will be given to each participant for home use. You will be given instructions and shown how to monitor your blood pressure.

You will be provided with a calendar to record the date and time of each dose, and your blood pressure reading before taking the drug. Missed doses should also be recorded. You must also bring the study drug bottle to each study visit so the research nurse can count any remaining pills.

A drug list will be given to you to record drugs taken within 4 weeks before you enrolled on the study and while on study. A new list will be provided during each clinic visit. You should not start a new prescription or over-the-counter drug before talking with the study doctor, except in the case of a medical emergency.

Study Visits:

At Week 1:

* You will be asked about any drugs you may be taking.
* Your performance status will be recorded.
* You will complete the questionnaire about kidney cancer care. This questionnaire will take about 5 minutes to complete.
* Women who are able to become pregnant will have a blood (about 1 teaspoon) or urine pregnancy test.

At Week 3:

* Your medical history will be recorded.
* You will have a physical exam.
* Your performance status will be recorded.
* You will have an ECG.
* Blood (about 2 tablespoons) will be drawn for routine testing to check your thyroid function.
* Urine (about 2 tablespoons) will be collected for routine testing.
* You will complete the questionnaire about kidney cancer care.

At Weeks 5 and 9, you will be called and asked if you have had any side effects. This call should take about 10 minutes.

At Weeks 7 and 12:

* Your medical history will be recorded.
* You will have a physical exam.
* Your performance status will be recorded.
* Blood (about 2 tablespoons) will be drawn for routine testing and to check your thyroid function.
* Urine (about 2 tablespoons) will be collected for routine testing.
* You will complete the questionnaire about kidney cancer care.
* You will have a CT scan of chest and abdomen to check the status of the disease.
* At Week 12 only, you will have an ECG.

At Week 13, you will have surgery to remove the kidney tumor. You will receive a separate consent form for this surgery.

At Week 19:

* Your medical history will be recorded.
* You will have a physical exam.
* Your performance status will be recorded.
* Blood (about 2 tablespoons) will be drawn for routine testing and to check your thyroid function.
* You will complete the questionnaire about kidney cancer care.
* You will have a CT scan of chest and abdomen to check the status of the disease.
* If you have been treated for high blood pressure while taking the drug, your blood pressure will be monitored and your blood pressure medication will be reduced. Once your blood pressure reaches a certain level, this will be managed by your primary care doctor.

After Week 19, every 4 months (+/- 2 weeks) for the first 1 year, every 6 months (+/- 2 weeks) for the third and fourth year, then every year (+/- 1 month) for a total of 5 years post surgery:

* Your medical history will be recorded.
* You will have a physical exam.
* Your performance status will be recorded.
* You will have a CT scan of the chest and abdomen to check the status of the disease.
* Blood (about 2 tablespoons) will be drawn for routine testing and to check your thyroid function.
* You will complete the questionnaire about kidney cancer care (only during the first 2 years).

Length of Study:

You will take axitinib for up to 12 weeks. You will stop taking axitinib earlier than expected if the disease gets worse or if you have severe side effects. In both cases, you will move on to surgery after axitinib has been stopped.

After surgery, you will be contacted by the study staff every 4 months (+/- 2 weeks) for 1 year, every 6 months (+/- 2 weeks) for the next 2 years and every 12 months (+/- 1 month) for 2 more years (for a total of 5 years after surgery).

This is an investigational study. Axitinib is FDA approved and commercially available to treat advanced kidney cancer in adults when 1 previous drug treatment for this disease has not worked. In this study, it is being used for research purposes.

Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.

Neoadjuvant Axitinib in Locally Advanced Renal Cell Carcinoma (RCC)

A Phase II Clinical Trial Examining the Impact Of Neoadjuvant Axitinib On Primary Tumor Response In Patients With Locally Advanced Clear Cell Renal Cell Carcinoma

Objective response rate is defined as Complete Response (CR)+ Partial Response (PR) and evaluated when CT abdomen is done after 12 weeks of treatment. Per Response Evaluation Criteria in Solid Tumors Criteria ( RECIST v1.0) Complete Response (CR) is complete disappearance of renal mass; and, Partial Response (PR) is \>= 30% decrease in the largest diameter (LD) of the renal mass taking as reference the baseline largest diameter.

Disease-free survival is the time from on-treatment to first relapse or death (whichever comes first). Disease free survival was estimated using the Kaplan-Meier method. Participants are still being followed for the secondary outcome measures.

Overall survival is defined as the time from randomization until death due to any cause. Overall Survival was estimated using the Kaplan-Meier method. Participants are still being followed for the secondary outcome measures.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Testing AZD1775 in Advanced Solid Tumors That Have a Mutation Called SETD2	NCT03284385	Clear Cell Rena... Locally Advance... Locally Advance... Metastatic Mali... Metastatic Rena... Stage III Renal... Stage IV Renal ...	Adavosertib	18 Years -	National Cancer Institute (NCI)
Neoadjuvant Axitinib in Locally Advanced Renal Cell Carcinoma (RCC)	NCT01263769	Kidney Cancer	Axitinib	18 Years -	M.D. Anderson Cancer Center
Testing AZD1775 in Advanced Solid Tumors That Have a Mutation Called SETD2	NCT03284385	Clear Cell Rena... Locally Advance... Locally Advance... Metastatic Mali... Metastatic Rena... Stage III Renal... Stage IV Renal ...	Adavosertib	18 Years -	National Cancer Institute (NCI)
Neoadjuvant Axitinib in Locally Advanced Renal Cell Carcinoma (RCC)	NCT01263769	Kidney Cancer	Axitinib	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for locally advanced clear cell renal cell carcinoma