Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Adenocarcinoma

Prostatic Neoplasms

Neoplasm Metastasis

Lymphatic Metastasis

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplastic Processes

All Drugs and Chemicals

Antineoplastic Agents

Micronutrients

Vitamins

Androgens

Hormones

Axitinib

Androgen Antagonists

Ascorbic Acid

Methyltestosterone

Testosterone

Testosterone undecanoate

Testosterone enanthate

Testosterone 17 beta-cypionate

Estrogens, Conjugated (USP)

Estrogens

Hormone Antagonists

Antioxidants

Protective Agents

Trace Elements

Antineoplastic Agents, Hormonal

Anabolic Androgenic Steroids

Anabolic Agents

Protein Kinase Inhibitors

Enzyme Inhibitors

Vitamin C

Patients receive antiandrogen therapy per standard care and axitinib PO BID for 4 months. Patients then undergo radical prostatectomy and pelvic lymph node dissection.

Patients receive antiandrogen therapy per standard care for 4 months and then undergo radical prostatectomy and pelvic lymph node dissection.

Antiandrogen Therapy

Radical Prostatectomy

Regional Lymph Node Dissection

Amado J Zurita Saavedra

This randomized phase IIA trial studies how well antiandrogen therapy works with or without axitinib before surgery in treating patients with previously untreated prostate cancer that is known or suspected to have spread to lymph nodes. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as antiandrogen therapy may lessen the amount of androgen made by the body. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if antiandrogen therapy is more effective with or without axitinib before surgery in treating patients with prostate cancer.

PRIMARY OBJECTIVES:

I. To compare the proportion of patients progression-free one year after treatment with axitinib plus androgen deprivation versus (vs.) androgen deprivation therapy alone and surgery in newly diagnosed prostate cancer patients with lymph node metastases (TxN1M0 or TxNxM1a) or clinical suspicion of lymph node metastases.

SECONDARY OBJECTIVES:

I. To compare the rate of pathologic complete response (pCR) in the primary tumor.

II. To evaluate time to progression. III. Describe the perioperative and postoperative morbidity of pre-surgical treatment.

IV. Evaluate the effects of a 6-month time course of androgen deprivation with or without axitinib in prostate cancer tissue and blood.

V. Develop a prospective tissue archive of prostate tumors that have metastasized to lymph nodes.

OUTLINE:

Patients receive antiandrogen therapy per standard care for 8 weeks.

Patients are then randomized to 1 of 2 treatment arms.

ARM I: Patients receive antiandrogen therapy per standard care and axitinib orally (PO) twice daily (BID) for 4 months. Patients then undergo radical prostatectomy and pelvic lymph node dissection.

ARM II: Patients receive antiandrogen therapy per standard care for 4 months and then undergo radical prostatectomy and pelvic lymph node dissection.

After completion of study treatment, patients are followed up at 1 and 3 months, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then yearly thereafter.

Antiandrogen Therapy With or Without Axitinib Before Surgery in Treating Patients With Previously Untreated Prostate Cancer With Known or Suspected Lymph Node Metastasis

Pre-Surgical Androgen Deprivation Therapy With or Without Axitinib in Previously Untreated Prostate Cancer Patients With Known or Suspected Lymph Node Metastasis

Time to Prostate-specific antigen (PSA)-progression measured from the date of radical prostatectomy to the occurrence of a serum PSA \>1.0 ng/mL (confirmed by a second measurement at least 2 weeks apart). PSA-monitoring every 3 months after surgery for the first 12 months, every 4 months in the second year, every 6 months in the third to fifth year, and yearly thereafter until PSA or radiologic progression.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Melanoma

Melanoma, Cutaneous Malignant

Skin Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Anti-Infective Agents

Alovudine

Antiviral Agents

NEOADJUVANT TREATMENT: Patients receive 18F-FLT IV and undergo a PET/CT scan approximately 60 minutes later. Within 2 weeks, patients receive encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive 18F-FLT IV and undergo a second PET/CT scan approximately 60 minutes later.

SURGICAL RESECTION: Within 2 weeks of completing therapy with encorafenib and binimetinib, patients undergo surgery.

ADJUVANT TREATMENT: Within 2-7 days after surgery, patients resume treatment with encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 11 cycles in the absence of disease progression or unacceptable toxicity.

Binimetinib

Computed Tomography

Conventional Surgery

Encorafenib

Fluorothymidine F-18

Positron Emission Tomography

Leslie A Fecher

This phase II trial studies how well encorafenib and binimetinib work before surgery in treating patients with BRAF V600-mutated stage IIIB-D melanoma that has spread to the lymph nodes. Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This trial also studies how well 18F-FLT positron emission tomography (PET)/computed tomography (CT) works in predicting the response of melanoma to encorafenib and binimetinib. 18F-FLT is an imaging agent, sometimes called a tracer. PET and CT are types of imaging scans. Using 18F-FLT PET/CT together with encorafenib and binimetinib may provide more information on melanoma over time.

PRIMARY CLINICAL OBJECTIVE:

I. To evaluate the pathologic complete response (pCR) rate of neoadjuvant treatment with encorafenib and binimetinib.

SECONDARY CLINICAL OBJECTIVES:

I. To determine response rate (RR) (Response Evaluation Criteria in Solid Tumors \[RECIST\]), disease-free survival (DFS) and overall survival (OS).

II. To describe correlation of pCR with RR, DFS and OS. III. To assess safety and toxicity.

CORRELATIVE SCIENCE OBJECTIVES:

I. To evaluate CD8 positive (+) T cell infiltration and Ki-67 status in tumor or tumor bed pre, during, and post neoadjuvant treatment and the change in CD8+ tumor infiltrating lymphocyte (TIL) with neoadjuvant treatment and correlate with clinical response.

II. To compare local review for pathologic response with central pathology review.

III. To assess the correlation between change in fluorothymidine F-18 (18F-FLT) PET/CT uptake and change in Ki-67.

IMAGING OBJECTIVES:

I. To compare the change in 18F-FLT PET/CT uptake (from baseline to post-neoadjuvant therapy) among patients with and without pathologic complete response.

II. To compare post-neoadjuvant 18F-FLT PET/CT uptake among patients with and without pathologic complete response.

III. To estimate an optimal threshold for prediction of pathologic complete response using i) change in 18F-FLT PET/CT uptake, and ii) post-neoadjuvant 18F-FLT PET/CT uptake.

IV. To assess the correlation between change in 18F-FLT PET/CT uptake and change in Ki-67.

OUTLINE:

NEOADJUVANT TREATMENT: Patients receive 18F-FLT intravenously (IV) and undergo a PET/CT scan approximately 60 minutes later. Within 2 weeks, patients receive encorafenib orally (PO) once daily (QD) and binimetinib PO twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive 18F-FLT IV and undergo a second PET/CT scan approximately 60 minutes later.

SURGICAL RESECTION: Within 2 weeks of completing therapy with encorafenib and binimetinib, patients undergo surgery.

ADJUVANT TREATMENT: Within 2-7 days after surgery, patients resume treatment with encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 11 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, then every 6 months for 3 years.

Testing Treatment With Encorafenib and Binimetinib Before Surgery for Melanoma With Lymph Node Involvement

A Phase II Neoadjuvant Study of Encorafenib With Binimetinib in Patients With Resectable Locoregional Metastases From Cutaneous or Unknown Primary Melanoma (Stages III N1B/C/D)

Ki-67 immunohistochemistry in tumor cells will be graded as a percentage of total number of tumor cells with nuclear staining (to the nearest 10%) over 10 high powered fields (at 20 x magnification).

Will be estimated and 90% confidence intervals (CI) adjusting for the first stage analysis will be provided.

Will be compared among patients with and without a pCR. Distributional summaries of the continuous percent change in 18F-FLT PET/CT maximum standardized uptake value (SUVmax) will be reported, where percent change is defined as (baseline SUVmax - post-neoadjuvant SUVmax)/(baseline SUVmax)\*100%. The comparison of percent change in SUVmax between pCR and non-pCR patients will be performed using a one-sided nonparametric Wilcoxon rank sum test with an alpha level of 0.05. Will also report distributional summaries and comparisons for percent change in 18F-FLT PET/CT peak SUV (SUVpeak); however, the prespecified primary comparison will be based on 18F-FLT PET/CT SUVmax.

OS distributions will be estimated using the Kaplan-Meier method. Median OS will be described with 95% confidence intervals. Clinical data from unevaluable patients will be summarized separately.

DFS distributions will be estimated using the Kaplan-Meier method. Median DFS will be described with 95% confidence intervals. Clinical data from unevaluable patients will be summarized separately.

Will be evaluated based on international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors guideline (version 1.1) and estimated with 95% confidence interval. Clinical data from unevaluable patients will be summarized separately.

Will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version(v.) 5.0. All treatment-emergent and baseline adverse events and hematological/biochemical toxicities based on laboratory measurements, as well as drug related AEs, will be summarized by NCI CTCAE v. 5.0 worst grade. The incidence of deaths and treatment-emergent serious adverse events (defined as number of patients experiencing the AE divided by all treated patients) will be summarized. Also, the incidence of adverse events leading to discontinuation of investigational product and/or withdrawal from the study will be summarized and listed.

Will be based on the two-sample t-test using two-sided type I error rate of 0.1. If normality assumption is not appropriate, Wilcoxon rank sum test will be used during the analysis. Using the median change value, cases will be divided to high and low change groups. Will be assessed and summarized using the descriptive statistics. Will be compared among patients achieving a pCR versus no pCR.

Will be based on the two-sample t-test using two-sided type I error rate of 0.1. If normality assumption is not appropriate, Wilcoxon rank sum test will be used during the analysis. Using the median change value, cases will be divided to high and low change groups. Will be assessed and summarized using the descriptive statistics

The concordance of pCR assessed based on local review versus central pathology review will be evaluated. Kendall's Tau test will be used for this comparison.

Will be compared among patients with and without a pCR. Distributional summaries of the post-neoadjuvant 18F-FLT PET/CT SUVmax will be reported. The comparison SUVmax between pCR and non-pCR patients will be performed using a one-sided nonparametric Wilcoxon rank sum test with an alpha level of 0.05. Will also report distributional summaries and comparisons for post-neoadjuvant in 18F-FLT PET/CT peakSUV.

Will be estimated using change in 18F-FLT PET/CT uptake. Diagnostic performance of percent change in 18F-FLT PET/CT SUVmax (from the baseline scan to the post-neoadjuvant scan) as a marker for pCR status will be assessed using receiver operating characteristic curve (ROC) analysis. In particular, the empirical area. The corresponding performance of the optimal threshold (measured via sensitivity and specificity) will be estimated using cross-validation under the receiver operating characteristic curve (ROC AUC) will be reported, along with corresponding 95% confidence interval. In addition, will formally test if the ROC AUC exceeds 0.5 using a one-sided test with an alpha level of 0.05. The optimal threshold (binary cutpoint) of continuous percent change in SUVmax will be estimated by means of the Youden index. A 95% confidence interval for the optimal threshold will be estimated using the bootstrap technique to properly reflect sampling variability.

The correlation between percent change in continuous SUVmax and percent change in the continuous Ki67 score will be estimated using the Spearman correlation coefficient. A one-sided correlation test with null hypothesis of zero correlation will be conducted at alpha level of 0.05. The corresponding confidence interval for the estimated Spearman correlation coefficient will also be reported. Correlation between change in 18F-FLT PET/CT and the early change in tumor cell Ki-67 (from baseline to the week 2 interim biopsy) will also be separately estimated. The corresponding correlation with percent change in 18F-FLT PET/CT SUVpeak will also be reported.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Antiandrogen Therapy With or Without Axitinib Before Surgery in Treating Patients With Previously Untreated Prostate Cancer With Known or Suspected Lymph Node Metastasis	NCT01409200	Metastatic Mali... Prostate Ductal... Stage III Prost... Stage IV Prosta...	Antiandrogen Th... Axitinib Radical Prostat... Regional Lymph ...	18 Years -	M.D. Anderson Cancer Center
Testing Treatment With Encorafenib and Binimetinib Before Surgery for Melanoma With Lymph Node Involvement	NCT04221438	Melanoma of Unk... Metastatic Mali... Pathologic Stag... Pathologic Stag... Pathologic Stag... Recurrent Cutan...	Binimetinib Computed Tomogr... Conventional Su... Encorafenib Fluorothymidine... Positron Emissi...	18 Years -	Eastern Cooperative Oncology Group
Testing Treatment With Encorafenib and Binimetinib Before Surgery for Melanoma With Lymph Node Involvement	NCT04221438	Melanoma of Unk... Metastatic Mali... Pathologic Stag... Pathologic Stag... Pathologic Stag... Recurrent Cutan...	Binimetinib Computed Tomogr... Conventional Su... Encorafenib Fluorothymidine... Positron Emissi...	18 Years -	Eastern Cooperative Oncology Group

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