Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Adenocarcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

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

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Adagrasib

Tyrosine Kinase Inhibitors

Tyrosine

Patients with advanced solid tumors and the following:

* HRAS-mutant and/or amplified tumors (any solid tumor type)
* HRAS overexpression (only for HNSCC tumors)
* KRAS and/or NRAS and/or HRAS-mutant and/or amplified for NSCLC or CRC
* KRAS-mutant and/or amplified PDAC

Patients who have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic RCC with predominantly clear cell subtype

Patients with KRAS G12C-mutant locally advanced or metastatic NSCLC who have received at least 1 prior systemic therapy for advanced or metastatic NSCLC

KO-2806

Cabozantinib

Clinical Operations

Xiomara Menendez, RN

Christopher Lim

Amy Whitaker

Nancy Olsen

Emily McClure, RN

Jessica Ley

Christina Caldwell

UW Carbone Cancer Center - Cancer Connect

This first-in-human (FIH) dose-escalation and dose-validation/expansion study will assess KO-2806, a farnesyl transferase inhibitor (FTI), as a monotherapy and in combination, in adult patients with advanced solid tumors.

KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors

Phase 1, First-in-Human, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of KO-2806 When Administered as Monotherapy and in Combination Therapy in Adult Patients With Advanced Solid Tumors

Area under the curve from time zero to last measurable concentration for KO-2806 (in the absence and presence of food) and combination agent.

Area under the curve from time zero to infinity post administration for KO-2806 (in the absence and presence of food) and combination agent

Maximum plasma concentration (Cmax) of KO-2806 (in the absence and presence of food) and the combination agent

Minimum plasma concentration (Cmin) of KO-2806 (in the absence and presence of food) and the combination agent

Time to maximal concentration (Tmax) of KO-2806 (in the absence and presence of food) and the combination agent

Estimated terminal elimination rate constant of KO-2806 and the combination agent

Half-life (t1/2) of KO-2806 (in the absence and presence of food) and the combination agent

Total apparent clearance (CL/F) of KO-2806 and the combination agent

Total apparent volume of distribution (Vd/F) of KO-2806 and the combination agent

QT interval corrected for heart rate (HR) using Fridericia's formula (QTcF) for KO-2806 monotherapy and in combination

Renal clearance of KO-2806 excretion in urine

Mirati Therapeutics Inc.

Kura Oncology, Inc.

Digestive System Diseases

Gland and Hormone Related Diseases

Stomach Neoplasms

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Cancer

Pancreatic Cancer

Antirheumatic Agents

Anti-Infective Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Immunomodulating Agents

Carbamide Peroxide

Mesna

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + escalating doses of anti-KRAS G12V mTCR PBL + high-dose aldesleukin

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + MTD of anti-KRAS G12V mTCR PBL + high-dose aldesleukin

Days -7 and -6: Cyclophosphamide 60 mg/kg/day x 2 days IV in 250 mL D5W infused simultaneously with mesna 15 mg/kg/day over 1 hour x 2 days.

Days -7 to -3: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.

Day 0: Cells will be infused intravenously on the Patient Care Unit over 20-30 minutes (2-4 days after the last dose of fludarabine).

Anti-KRAS G12V mTCR PBL

Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 3 days (maximum 9 doses).

NCI SB Immunotherapy Recruitment Center

For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center

James C Yang, M.D.

Background:

A new cancer therapy involves taking white blood cells from a person, growing them in the lab, genetically modifying them, then giving them back to the person. This therapy is called gene transfer using anti-KRAS G12V mTCR cells.

Objective:

To see if anti-KRAS G12 V mTCR cells are safe and can shrink tumors.

Eligibility:

Adults at least 18 years old with cancer that has the KRAS G12V molecule on the surface of tumors.

Design:

In another protocol, participants will:

Be screened

Have cells harvested and grown

Have leukapheresis

In this protocol, participants will have the procedures below.

Participants will be admitted to the hospital.

Over 5 days, participants will get 2 chemotherapy medicines as an infusion via catheter in the upper chest.

A few days later, participants will get the anti-KRAS G12V mTCR cells via catheter.

For up to 3 days, participants will get a drug to make the cells active.

A day after getting the cells, participants will get a drug to increase their white blood cell count. This will be a shot or injection under the skin.

Participants will recover in the hospital for 1-2 weeks. They will have lab and blood tests.

Participants will take an antibiotic for at least 6 months.

Participants will have visits every few months for 2 years, and then as determined by their doctor.

Visits will be 1-2 days. They will include lab tests, imaging studies, and physical exam. Some visits may include leukapheresis or blood drawn.

Participants will have blood collected over several years.

Background:

* We generated an HLA-A\*11:01-restricted murine T-cell receptor (mTCR) that specifically recognizes the G12V-mutated variant of KRAS (and other RAS family genes), expressed by many human cancers and constructed a single retroviral vector that contains alpha and beta chains that confer recognition of this antigen when transduced into PBL.
* In co-cultures with HLA-A\*11:01+ target cells expressing this mutated oncogene, mTCR transduced T cells lyse target cells and secrete IFN-gamma with high specificity.

Objectives:

Primary objectives:

* Phase I: Determine the safety of administering PBL transduced with anti-KRAS G12V mTCR in concert with preparative lymphodepletion and high-dose interleukin-2 (IL-2; aldesleukin).
* Phase II: Determine if anti-KRAS G12V mTCR-transduced PBL can mediate the regression of tumors harboring the RAS G12V mutation.

Eligibility:

Patients must be/have:

* Age greater than or equal to 18 years and less than or equal to 72 years
* HLA-A\*11:01 positive
* Metastatic or unresectable RAS G12V-expressing cancer which has progressed after standard therapy (if available).

Patients may not have:

-Allergies or hypersensitivities to high-dose aldesleukin, cyclophosphamide or fludarabine.

Design:

* This is a Phase I/II, single center study of PBL transduced with anti-KRAS G12V mTCR in HLA-A\*11:01 positive patients with advanced solid tumors expressing G12V mutated RAS.
* PBMC obtained by leukapheresis will be cultured in the presence of anti-CD3 (OKT3) and aldesleukin in order to stimulate T-cell growth.
* Transduction is initiated by exposure of these cells to retroviral vector supernatant containing replication-incompetent virus encoding the anti-KRAS G12V mTCR.
* All patients will receive a non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine.
* On day 0, patients will receive their PBL transduced with the anti-KRAS G12V mTCR and will then begin high-dose aldesleukin.
* A complete evaluation of lesions will be conducted approximately 6 weeks (+/- 2 weeks) after treatment.
* The study will be conducted using a phase I/II Simon minimax design, with two separate

cohorts for the Phase II component: Cohort 2a, patients with RAS G12V pancreatic

cancer, and Cohort 2b, patients with RAS G12V non-pancreatic cancer.

-A total of up to 110 patients may be required; approximately 24 patients in the phase I portion of the study and 86 (41, plus an allowance of up to 2 non-evaluable per phase II cohort) patients in the phase II portion of the study.

Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients

A Phase I/II Study Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients

.All IPD recorded in the medical record will be shared with intramural investigators upon request.

Percentage of patients who have a clinical response (PR+CR) to treatment (objective tumor regression)

Grade and type of toxicity per dose level; fraction of patients who experience a DLT at a given dose level, and number and grade of each type of DLT

National Cancer Institute (NCI)

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + escalating doses of anti-KRAS G12D mTCR PBL + highdose aldesleukin

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + MTD of anti-KRAS G12D mTCR PBL + high-dose aldesleukin

Days -7 to -3: Fludarabine 25 mg/m\^2/day IVPB daily over 30 minutes for 5 days.

anti-KRAS G12D mTCR PBL

Background:

A new cancer therapy takes white blood cells from a person, grows them in a lab, genetically changes them, then gives them back to the person. Researchers think this may help attack tumors in people with certain cancers. It is called gene transfer using anti-KRAS G12D mTCR cells.

Objective:

To see if anti-KRAS G12D mTCR cells are safe and cause tumors to shrink.

Eligibility:

Adults ages 18-72 who have cancer with a molecule on the tumors that can be recognized by the study cells

Design:

Participants will be screened with medical history, physical exam, scans, photography, and heart, lung, and lab tests.

An intravenous (IV) catheter will be placed in a large vein in the chest.

Participants will have leukapheresis. Blood will be removed through a needle in an arm. A machine will divide the blood and collect white blood cells. The rest of the blood will be returned to the participant through a needle in the other arm.

A few weeks later, participants will have a hospital stay. They will:

* Get 2 chemotherapy medicines by IV over 5 days.
* Get the changed cells through the catheter. Get up to 9 doses of a medicine to help the cells. They may get a shot to stimulate blood cells.
* Recover in the hospital for up to 3 weeks. They will provide blood samples.

Participants will take an antibiotic for at least 6 months.

Participants will have several follow-up visits over 2 years. They will repeat most of the screening tests and may have leukapheresis.

Participants blood will be collected for several years.

Background:

* We generated an HLA-A11:01-restricted murine T-cell receptor (mTCR) that specifically recognizes the G12D-mutated variant of KRAS (and other RAS family genes), expressed by many human cancers and constructed a single retroviral vector that contains alpha and beta chains that confer recognition of this antigen when transduced into PBL.
* In co-cultures with HLA-A11:01+ target cells expressing this mutated oncogene, mTCR transduced T-cells lyse target cells and secrete IFN-gamma with high specificity.

Objectives:

-Primary objectives:

* Phase I: Determine the safety of administering PBL transduced with anti-KRAS G12D mTCR in concert with preparative lymphodepletion and high-dose interleukin-2 (IL-2; aldesleukin).
* Phase II: Determine if anti-KRAS G12D mTCR-transduced PBL can mediate the regression of tumors harboring the RAS G12D mutation.

Eligibility:

* Patients must be/have:

  * Age greater than or equal to 18 years and less than or eqaul to 72 years
  * HLA-A\*11:01 positive
  * Metastatic or unresectable RAS G12D-expressing cancer which has progressed after standard therapy (if available).
* Patients may not have:

  * Allergies or hypersensitivities to high-dose aldesleukin, cyclophosphamide, or fludarabine.

Design:

* This is a phase I/II, single center study of PBL transduced with anti-KRAS G12D mTCR in HLA-A\*11:01 positive patients with advanced solid tumors expressing G12D mutated RAS.
* PBMC obtained by leukapheresis will be cultured in the presence of anti-CD3 (OKT3) and aldesleukin in order to stimulate T-cell growth.
* Transduction is initiated by exposure of these cells to retroviral vector supernatant containing replication-incompetent virus encoding the anti-KRAS G12D mTCR.
* All patients will receive a non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine.
* On Day 0, patients will receive their PBL transduced with the anti-KRAS G12D mTCR and will then begin high-dose aldesleukin.
* A complete evaluation of lesions will be conducted approximately 6 weeks (plus-minus 2 weeks) after treatment.
* The study will be conducted using a phase I/II Simon minimax design, with two separate cohorts for the Phase II component: Cohort 2a, patients with RAS G12D pancreatic cancer, and Cohort 2b, patients with RAS G12D non-pancreatic cancer.
* A total of up to 70 patients may be required; approximately 24 patients in the Phase I portion of the study and 46 (21, plus an allowance of up to 2 non-evaluable per Phase II cohort) patients in the Phase II portion of the study.

Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12D Variant of Mutated RAS in HLA-A*11:01 Patients

A Phase I/II Study Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12D Variant of Mutated RAS in HLA-A*11:01 Patients

.All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@All collected IPD will be shared with collaborators under the terms of collaborative agreements.

Symptoms and General Pathology

Carcinoma, Squamous Cell

Recurrence

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Tipifarnib

Adult participants with R/M HNSCC whose tumors harbor PI3KCA (activating) mutations and/or amplifications

Adult participants with R/M HNSCC whose tumors have increased HRAS dependency, defined as HRAS overexpression

Alpelisib

Khaleda Khan

Victoria M Villaflor, MD

Cesar A Perez, MD

Ranee Mehra, MD

Tracey K Adams, RN, BA

Peggy Fitzpatrick, MSN

Tanguy Y Seiwert, MD

Glenn J Hanna, MD

Jessica Ley, MD

Douglas R Adkins, MD

Susan Korte

Alan L Ho, MD, PhD

Kasey Stragand, RN

Dan P Zandberg, MD

Tiffany Thomas, BSN, RN

Randall S Hughes, MD

Jessie (Xiaoyan) Jia, MS RN OCN CCRP

Maura L Gillison, MD, PhD

Justine Y Bruce, MD

This phase 1/2 combination trial of tipifarnib, a farnesyltransferase inhibitor, and alpelisib, a PI3K inhibitor in participants with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) whose tumors overexpress the HRAS protein and/or are PIK3CA-mutated and/or PIK3CA-amplified.

Combination Trial of Tipifarnib and Alpelisib in Adult Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)

A Phase 1/2 Open-label, Biomarker-defined Cohort Trial to Evaluate the Safety, Determine the Recommended Combination Dosing, and Assess Early Antitumor Activity of Tipifarnib and Alpelisib for the Treatment of Adult Participants Who Have HRAS-overexpressing and/or PIK3CA-mutated and/or - Amplified Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Rate of DLT per dose level and Descriptive statistics of adverse events per the NCI CTCAE v 5.0

Overall confirmed response rate (CR + PR) and Median duration of response

Disease control rate (CR + PR + SD), Median duration of disease control, Rate of SD, Median duration of SD

Peak drug concentration for single dose and multiple dose

Time to reach peak concentration following drug administration for single dose and multiple dose

Area under the concentration-time curve from time zero to time of last measurable concentration for single dose and multiple dose

Area under the concentration-time curve during a dosage interval for single dose and multiple dose

Area under the concentration-time curve from time zero to infinity for single dose

Apparent total clearance of the drug after administration for single dose and multiple dose

Apparent volume of distribution after administration for single dose and multiple dose

Time required for the amount of drug in the body to decrease by half for single dose and multiple dose

Ratio of accumulation of a drug after multiple doses compared to a single dose

Median PFS and Proportion of participants alive and without progression at 6 months

Median OS and Proportion of participants alive at 12 months

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors	NCT06026410	Solid Tumors Wi... Non Small Cell ... Colorectal Canc... Pancreatic Duct... Clear Cell Rena...	KO-2806 Cabozantinib Adagrasib	18 Years -	Kura Oncology, Inc.
Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients	NCT03190941	Pancreatic Canc... Gastric Cancer Gastrointestina... Colon Cancer Rectal Cancer	Cyclophosphamid... Fludarabine Anti-KRAS G12V ... Aldesleukin	18 Years - 72 Years	National Institutes of Health Clinical Center (CC)
Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12D Variant of Mutated RAS in HLA-A*11:01 Patients	NCT03745326	Gastrointestina... Pancreatic Canc... Gastric Cancer Colon Cancer Rectal Cancer	Cyclophosphamid... Fludarabine Aldesleukin anti-KRAS G12D ...	18 Years - 72 Years	National Institutes of Health Clinical Center (CC)
Combination Trial of Tipifarnib and Alpelisib in Adult Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)	NCT04997902	HNSCC	Tipifarnib Alpelisib	18 Years -	Kura Oncology, Inc.

Spots Global Cancer Trial Database for hras

Every month we try and update this database with for hras cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for hras

Every month we try and update this database with for hras cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hras cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.