Neoplasms

All Conditions

Symptoms and General Pathology

Mouth and Tooth Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Mouth Neoplasms

Salivary Gland Neoplasms

Laryngeal Neoplasms

Oropharyngeal Neoplasms

Lip Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Neoplasms, Squamous Cell

Mouth Diseases

Stomatognathic Diseases

Salivary Gland Diseases

Otorhinolaryngologic Neoplasms

Laryngeal Diseases

Respiratory Tract Diseases

Respiratory Tract Neoplasms

Otorhinolaryngologic Diseases

Pharyngeal Neoplasms

Pharyngeal Diseases

Oral Squamous Cell Carcinoma

Oral Cancer

Laryngeal Cancer

Hypopharyngeal Cancer

Lip and Oral Cavity Cancer

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Starting on day 7, patients also receive BAY 1895344 PO BID on days 7-9 and 14-16 during cycle 1, and before and after each SBRT treatment during cycle 2 for a total of 9 doses. Beginning cycle 2, patients undergo SBRT starting between days 2 and 8 for 3 fractions with 2-3 days between fractions. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or PET-CT scan and collection of blood samples throughout the trial.

Biospecimen Collection

Computed Tomography

Elimusertib

Positron Emission Tomography

Quality-of-Life Assessment

Stereotactic Body Radiation Therapy

Yvonne M Mowery

This phase I trial evaluates the best dose, possible benefits and/or side effects of combination therapy with elimusertib (BAY 1895344), stereotactic body radiation, and pembrolizumab in treating patients with head and neck squamous cell cancer that has come back (recurrent) and cannot be removed by surgery (unresectable). BAY 1895344 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving BAY 1895344, stereotactic body radiation therapy in combination with pembrolizumab may shrink or stabilize head and neck squamous cell cancer for longer than treatment with radiation and immunotherapy without BAY 1895344.

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of BAY 1895344 with concurrent head and neck stereotactic body radiation therapy (SBRT) reirradiation and pembrolizumab.

II. To determine the recommended phase 2 dose (RP2D) of BAY 1895344 in combination with concurrent head and neck SBRT and pembrolizumab.

SECONDARY OBJECTIVE:

I. To observe and record anti-tumor activity (overall response rate, progression-free survival, and overall survival) of BAY 1895344, SBRT, and pembrolizumab for recurrent head and neck squamous cell carcinoma (HNSCC).

EXPLORATORY OBJECTIVE:

I. To identify predictive biomarkers of response to BAY 1895344, SBRT, and pembrolizumab, including, but not limited to the following: genetic alterations of ATM and other deoxyribonucleic acid (DNA) damage response genes, tumor mutational load, circulating tumor DNA, baseline tumor ATM expression, tumor PD-L1 expression, and change in circulating Ki67+ CD8+ T-cells relative to baseline.

OUTLINE: This is a dose-escalation study of BAY 1895344 and stereotactic body radiation therapy (SBRT) given with fixed-dose pembrolizumab.

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Starting on day 7, patients also receive BAY 1895344 orally (PO) twice daily (BID) on days 7-9 and 14-16 during cycle 1, and before and after each SBRT treatment during cycle 2 for a total of 9 doses. Beginning cycle 2, patients undergo SBRT starting between days 2 and 8 for 3 fractions with 2-3 days between fractions. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) scan and/or positron emission tomography (PET)-CT scan and collection of blood samples throughout the trial.

After completion of study treatment, patients are followed up every 13 weeks for at least 24 months.

Testing the Addition of an Anti-cancer Drug, BAY 1895344, With Radiation Therapy to the Usual Pembrolizumab Treatment for Recurrent Head and Neck Cancer

Phase I Trial of BAY 1895344 ATR Inhibitor Combined With Stereotactic Body Radiation Therapy and Pembrolizumab for Recurrent Head and Neck Squamous Cell Carcinoma

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Will investigate the association between potential predictive biomarkers of response to treatment. Tumor mutation burden will be categorized as high (above median) or low (equal to or below median). Other biomarker expression levels will be categorized as high versus absent/reduced. The chi-square or Fisher exact test will be used to study associations between expression levels and tumor response (complete response/partial response; stable/progressive disease). Associations with time-to-event endpoints will be investigated using the log rank test. Differences in change in circulating Ki67+ CD8+ T-cells relative to baseline between levels of tumor response will be explored using the t-test or non-parametric equivalent (e.g., Mann-Whitney) if appropriate. Cox regression will be used to explore associations between change in in circulating Ki67+ CD8+ T-cells and time-to-event endpoints. Other biomarkers will be analyzed similarly.

Will be assessed per Common Terminology Criteria for Adverse Events (CTCAE) version 5.

Will be assessed per CTCAE version 5. The frequency and percentage of adverse events will be provided overall and by dose level for any grade and attribution as well as for grade 3 or greater adverse events, at least possibly related to treatment.

A competing risk analysis will be conducted with local failure, distal failure, and death as competing events. The cumulative incidence and 95% confidence interval for local failure will be estimated. Time to each event will be measured from the start of treatment regimen (day 1 pembrolizumab).

Will be estimated using the method of Kaplan-Meier.

Defined as a complete response or partial response based on the Response Evaluation Criteria in Solid Tumors 1.1 criteria. The proportion of patients responding to the treatment regimen and corresponding 95% confidence interval estimates will be calculated.

Will be assessed by the Functional Assessment of Cancer Therapy for Patients With Head and Neck Cancer, version 4. The frequency and percentage of responses to the quality of life questionnaire will be summarized at 3, 6, and 12 months post-treatment and interpreted descriptively.

National Cancer Institute (NCI)

Nasopharyngeal Carcinoma

Disease Progression

Nasopharyngeal Neoplasms

Nasopharyngeal Diseases

Docetaxel

Bevacizumab

Atezolizumab

Carboplatin

Antibodies

Antibodies, Monoclonal

Cetuximab

Cisplatin

Immunoglobulins

Immunoglobulin G

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

Tubulin Modulators

Antimitotic Agents

Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.

Patients receive bevacizumab IV over 30-90 minutes on day 1 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-60 minutes on day 1 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.

Patients receive bevacizumab IV over 30-90 minutes on day 1 and atezolizumab over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.

Patients receive treatment as in Arm B or C above based on results of the Phase II trial.

Echocardiography

Magnetic Resonance Imaging

Site Public Contact

Saad A. Khan

Harlan A. Pinto

Aarti Bhatia

Gregory A. Masters

Irina G. Veytsman

Chukwuemeka (Emeka) V. Ikpeazu

Shannon B. Keating

Nabil F. Saba

Yoshihito Saito

Alison K. Conlin

Prem Sobti

Thomas E. Lad

Ameen Salahudeen

Ari J. Rosenberg

James A. Wallace

Joseph J. Merchant

Joshua Lukenbill

Richard L. Deming

Ranee Mehra

Mei Tang

Tanguy Y. Seiwert

Dan P. Zandberg

William V. Walsh

David M. King

Martha Mapalo

Samer S. Kasbari

Tarek M. Sabagh

Howard M. Gross

Rex B. Mowat

Minh Phan

This phase II/III compares the standard therapy (chemotherapy plus cetuximab) versus adding bevacizumab to standard chemotherapy, versus combination of just bevacizumab and atezolizumab in treating patients with head and neck cancer that has spread to other places in the body (metastatic or advanced stage) or has come back after prior treatment (recurrent). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of cancer cells. This may help keep cancer cells from growing. Cisplatin and carboplatin are in a class of chemotherapy medications known as platinum-containing compounds. They work by killing, stopping, or slowing the growth of cancer cells. Docetaxel is in a class of chemotherapy medications called taxanes. It stops cancer cells from growing and dividing and may kill them. The addition of bevacizumab to standard chemotherapy or combination therapy with bevacizumab and atezolizumab may be better than standard chemotherapy plus cetuximab in treating patients with recurrent/metastatic head and neck cancers.

PRIMARY OBJECTIVES:

I. To evaluate progression-free survival (PFS) of patients treated with chemotherapy plus cetuximab, chemotherapy plus bevacizumab, and atezolizumab plus bevacizumab. (Phase II) II. To evaluate the overall survival (OS) of patients treated with chemotherapy plus cetuximab to the superior arm from the phase II portion of the protocol. (Phase III)

SECONDARY OBJECTIVES:

I. To evaluate the OS for the subset of patients with high PD-L1 expression, defined as combined positive score (CPS) \>= 20% on all arms of treatment.

II. To evaluate the toxicity of each arm of treatment.

IMAGING OBJECTIVES:

I. To establish the correlation between fludeoxyglucose F-18 (18F-FDG) positron emission tomography (PET) and computed tomography (CT) neck imaging biomarkers (maximum standard uptake value \[SUVmax\], metabolic tumor volume \[MTV\], total lesion glycolysis \[TLG\], tumor volume) and expression of PD-L1 expression (Low versus high, defined as CPS \< 20 versus CPS \>= 20).

II. To determine if 18FDG-PET/CT and CT neck imaging biomarkers at baseline will predict treatment response at nine to twelve weeks post the initiation of treatment, PFS, and OS.

EXPLORATORY OBJECTIVE:

I. To establish the correlation between 18F-FDG PET and CT neck radiomics features and PD-L1 expressions (Low versus high - defined as CPS \< 20 versus CPS \>= 20).

OUTLINE: This is a randomized phase II trial followed by a randomized phase III trial.

PHASE II: Patients are randomized to 1 of 3 arms.

ARM A: Patients receive cetuximab intravenously (IV) over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or magnetic resonance imaging (MRI) throughout the trial. Patients may undergo echocardiography (ECHO) during screening.

ARM B: Patients receive bevacizumab IV over 30-90 minutes on day 1 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-60 minutes on day 1 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening.

ARM C: Patients receive bevacizumab IV over 30-90 minutes on day 1 and atezolizumab over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening.

PHASE III: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening.

ARM B: Patients receive treatment as in Arm B or C above based on results of the Phase II trial.

Patients undergo blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30 days and then every 3 months if patient is \< 2 years from randomization and every 6 months if patient is 2-5 years from randomization.

Testing the Use of Investigational Drugs Atezolizumab and/or Bevacizumab With or Without Standard Chemotherapy in the Second-Line Treatment of Advanced-Stage Head and Neck Cancers

A Phase II/III Trial of Chemotherapy + Cetuximab vs Chemotherapy + Bevacizumab vs Atezolizumab + Bevacizumab Following Progression on Immune Checkpoint Inhibition in Recurrent/Metastatic Head and Neck Cancers

The imaging textural features from radiomics analysis will be associated with the dichotomized PD-L1 expressions. First, proper transformation will be applied to the textural features as needed to address the distribution skewness. Second, Pearson or Spearman rank correlations will be calculated between all pairs of textural features to identify highly correlated features. Third, to address overfitting and high collinearity, machine learning techniques (e.g., LASSO or XGBoost) will be employed for feature selection during the association analysis with PD-L1 expressions.

Will be compared using a stratified log rank test.

The interaction of PD-L1 by treatment will also be evaluated in a Cox proportional hazards model.

The two-sample t-test will be used to compare the difference of baseline 18F -FDG PET /CT imaging biomarkers (maximum standardized uptake value \[SUVmax\], metabolic tumor volume \[MTV\], total lesion glycolysis \[TLG\], tumor volume) between low and high expression of PD-L1.

Determined by 18FDG-PET/CT and CT neck imaging biomarkers. To determine if 18FDG-PET/CT and CT neck imaging biomarkers at baseline will predict treatment response at nine to twelve weeks post-treatment, PFS, and OS Logistic regression model will be fit to assess the association of the 18F -FDG PET /CT imaging biomarkers (e.g., SUVmax, MTV, TLG, tumor heterogeneity, tumor volume) with binary treatment response at 9-12 weeks post treatment. Cox proportional hazards models will be fit to assess the association of 18F -FDG PET /CT imaging biomarkers with time-to-event outcomes (PFS or OS).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Testing the Addition of an Anti-cancer Drug, BAY 1895344, With Radiation Therapy to the Usual Pembrolizumab Treatment for Recurrent Head and Neck Cancer	NCT04576091	Clinical Stage ... Clinical Stage ... Recurrent Cutan... Recurrent Head ... Recurrent Hypop... Recurrent Laryn... Recurrent Oral ... Recurrent Oroph... Recurrent Paran... Recurrent Saliv... Stage III Cutan... Stage III Hypop... Stage III Laryn... Stage III Lip a... Stage III Major... Stage III Oroph... Stage III Sinon... Stage IV Cutane... Stage IV Hypoph... Stage IV Laryng... Stage IV Lip an... Stage IV Major ... Stage IV Oropha... Stage IV Sinona... Unresectable Cu... Unresectable He... Unresectable Hy... Unresectable La... Unresectable Or... Unresectable Or... Unresectable Pa... Unresectable Sa...	Biospecimen Col... Computed Tomogr... Elimusertib Pembrolizumab Positron Emissi... Quality-of-Life... Stereotactic Bo...	18 Years -	National Cancer Institute (NCI)
Testing the Use of Investigational Drugs Atezolizumab and/or Bevacizumab With or Without Standard Chemotherapy in the Second-Line Treatment of Advanced-Stage Head and Neck Cancers	NCT05063552	Clinical Stage ... Metastatic Head... Metastatic Hypo... Metastatic Lary... Metastatic Lip ... Metastatic Nasa... Metastatic Naso... Metastatic Phar... Metastatic Sino... Recurrent Head ... Recurrent Hypop... Recurrent Laryn... Recurrent Lip a... Recurrent Nasop... Recurrent Phary... Recurrent Sinon... Stage IV Hypoph... Stage IV Laryng... Stage IV Lip an... Stage IV Nasoph... Stage IV Oropha... Stage IV Sinona...	Atezolizumab Bevacizumab Biospecimen Col... Carboplatin Cetuximab Cisplatin Computed Tomogr... Docetaxel Echocardiograph... Magnetic Resona... Positron Emissi...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for stage iv sinonasal cancer ajcc v8