A Phase 2 Study of Bevacizumab, Erlotinib and Atezolizumab in Subjects with Advanced Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) Associated or Sporadic Papillary Renal Cell Cancer.
- NCT01130519
Primary Objective:
- To assess the complete response (CR) rate according to standard Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) in patients with 1) advanced RCC associated with HLRCC and 2) advanced sporadic/non-HLRCC papillary renal cell cancer treated with a combination of bevacizumab, erlotinib, and atezolizumab.
Secondary Objectives:
- To determine the safety and tolerability of the combination of bevacizumab, erlotinib, and atezolizumab.
- To determine the objective response rate (ORR) as complete response (CR) + partial
response (PR).
- To determine disease control rate (DCR) - confirmed response, or stable disease (SD) lasting for at least 6 months.
- To assess progression-free survival time (PFS) according to RECIST 1.1.
- To assess overall survival (OS).
- To assess the duration of response.
- To assess response to treatment using iRECIST.
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Protocol Number:
082203
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Principal Investigator:
Ryan Stephenson
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Phase:
Phase II
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Scope:
National
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Applicable Disease Sites:
Kidney
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Therapies Involved:
Chemotherapy multiple agents systemic
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Drugs Involved:
Atezolizumab (MPDL3280A)
BEVACIZUMAB
ERLOTINIB
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Read Inclusion & Exclusion Criteria
- INCLUSION CRITERIA:Patients must meet all the following criteria to be eligible for study enrolment:
- Diagnosis of advanced renal cell cancer (RCC) associated with hereditary leiomyomatosis and renal cell cancer (HLRCC) (cohorts 1 & 3) or sporadicon-HLRCC papillary RCC (cohort 2 & 4)
- Measurable disease outlined in Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- No more than two prior regimens targeting the vascular endothelial growth factor (VEGF) pathway; no prior bevacizumab therapy
- Age greater than or equal to 18 years.
- Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
- Patients must have normal organ and marrow function as defined below: white blood cell (WBC) count greater than or equal to 3,000/microL, absolute neutrophil count greater than or equal to 1,500/microL, platelet count greater than or equal to 100,000/microL, serum creatinine greater than or equal to 2 times the upper limit of reference range or creatinine clearance greater than or equal to 30 ml/min, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 times the upper limit of reference range, total bilirubin less than 1.5 times the upper limit of reference range ( less than 3 x upper limit of reference range in patients with Gilbert's disease), alkaline phosphatase less than or equal to 2.5 times the upper limit of reference range (or less than or equal to 5 times the upper limit of reference range if considered to be related to liver or bone metastases by the principal investigator (PI)
- Recovery from acute toxicity of prior treatment for RCC (to less than or equal to grade 1 the active version of Common Terminology Criteria for Adverse Events (CTCAE) or to a level permitted under other sections of Inclusion/ Exclusion criteria).
- At least 4 weeks from completion of major surgery and a healed surgical incision
- Negative pregnancy test (within 7 days of enrolment) in women of childbearing potential
- No myocardial infarction, gastrointestinal (GI) perforation/fistula, intra-abdominal abscess, cerebrovascular accidents within six months prior to study entry
- No coagulopathy or bleeding diathesis
- Ability to understand and the willingness to sign a written informed consent document.
- Archival tissue block or unstained tumor tissue available for correlative studiesEXCLUSION CRITERIA:
- Prior invasive malignancy of other histology, with the exception of adequately treated basal or squamous cell carcinoma of the skin, or any other malignancy for which the patient does not currently require treatment and/or has no evidence of disease for greater than or equal to 2 years.
- Patients with known brain metastases unless treated with an appropriate modality with no evidence of progression/recurrence for greater than 3 months
- Hypertension not controlled by medical therapy (resting systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg on at least two occasions over a 24 hour period despite optimal medical management).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure (New York Heart Association grade III or greater), unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
- Serious, non-healing wound or ulcer; bone fracture within 3 months prior to study entry
- Patient known to be human immunodeficiency virus (HIV)-positive and requiring antiretroviral therapy (due to the risk of potential drug interactions)
- Concomitant therapy with potent inhibitors of Cytochrome P450 3A4 (CYP450 3A4) (e.g., ketoconazole, verapamil etc.) or with potent CYP450 1A2 inhibitors (fluoroquinolone antibiotics including ciprofloxacin, levofloxacin, and norfloxacin; ticlodipine, cimetidine, amiodarone, etc. see Appendix C)
- Pregnant women are excluded from this study because bevacizumab and erlotinib are anti-cancer agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated on this study
- All men and women of childbearing potential must be willing to use effective contraception as determined by the principal investigator (including but not limited to abstinence, hormonal contraceptives (birth control pills, injections, or implants), intrauterine device (IUD), tubal ligation, vasectomy) from the time of enrolment to at least six months following the last dose of drug
- Any known hypersensitivity to bevacizumab, erlotinib or other excipients of these drugs
- Documented baseline proteinuria greater than 1000mg/day on 24-hour urine collection. Only patients with 1+ or greater proteinuria on urinalysis (UA) and a spot urine protein: creatinine ratio of greater than 0.5 will undergo a 24-hour urine collection for quantitation of proteinuria.
- Left ventricular ejection fraction less than 40% as measured on transthoracic echocardiogram.INCLUSION OF WOMEN AND MINORITIES:Both men and women and members of all races and ethnic groups are eligible for thistrial.
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.
Testing the Addition of Stereotactic Radiation Therapy With Immune Therapy for the Treatment of Patients With Unresectable or Metastatic Renal Cell Cancer.
- NCT05327686
Primary Objective:
To determine whether the addition of stereotactic ablative radiotherapy (SABR) to the primary tumor in combination with immunotherapy improves outcomes compared to immunotherapy alone in patients with metastatic, unresected, renal cell carcinoma (RCC).
The primary endpoint is nephrectomy and radiographic progression-free survival (nrPFS) with progression determined as per iRECIST criteria.
Secondary Objectives:
- To assess the safety, toxicity and tolerability of the two treatment strategies as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5 in each treatment arm.
- To assess the objective response rate (ORR) by iRECIST in each treatment arm.
- Nephrectomy and radiographic progression-free survival excluding nephrectomies that were performed for non-protocol specified indications (nrPFS2).
- Radiographic progression-free survival (rPFS) .
- To assess overall survival (OS) in each treatment arm.
- To assess the time to subsequent second-line therapy or death in each treatment arm.
- To assess the rate of cytoreductive nephrectomy in each treatment arm.
- To assess treatment-free survival in patients who discontinue therapy for reason other than radiographic disease progression.
- To assess the ORR by RECIST version 1.1 and iRECIST in the primary renal mass.
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Protocol Number:
082305
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Principal Investigator:
Lara Hathout
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Phase:
Phase II
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Scope:
National
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Applicable Disease Sites:
Kidney
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Therapies Involved:
Chemotherapy multiple agents systemic
Radiotherapy
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Drugs Involved:
Axitinib
Cabozantinib (XL184)
IPILIMUMAB (MDX-010)
Lenvatinib (E7080/MK-7902)
Opdivo (Nivolumab)
Pembrolizumab (MK-3475)
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Read Inclusion & Exclusion Criteria
Inclusion Criteria:
- Pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma prior to registration
- Node-positive unresectable (TxN1Mx) or metastatic (TxNxM1) based on the following diagnostic workup:
- History/physical examination within 45 days prior to registration
- CT/magnetic resonance imaging (MRI) of the chest/abdomen/pelvis within 45 days prior to registration
- Patients must have IMDC intermediate (1-2 factors) or poor risk disease (>= 3 factors)
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- Patients with measurable disease (node positive or metastatic) as defined by RECIST version 1.1 excluding the primary renal tumor
- Patient not recommended for or refused immediate cytoreductive nephrectomy
- Candidate for standard of care therapy with either immuno-oncology (IO)-IO or IO-VEGF combination regimen
- Primary renal tumor measuring 20 cm or less in anterior to posterior dimension only on axial imaging
- Age >= 18
- Karnofsky performance status >= 60 within 45 days prior to registration
- Hemoglobin >= 8 g/dL (transfusions are allowed) (within 45 days prior to registration)
- Platelet count >= 50,000/mm^3 (within 45 days prior to registration)
- Absolute neutrophil count (ANC) >= 1500/mm^3 (within 45 days prior to registration)
- Calculated (Calc.) creatinine clearance >= 30 mL/min (within 45 days prior to registration)
- For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR >= 30 mL/min/1.73m^2 will be considered adequate
- Total bilirubin =< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) (within 45 days prior to registration)
- Aspartate aminotransferase and alanine aminotransferase (AST and ALT) =< 3 x upper limit of normal (ULN) or < 5 x ULN if hepatic metastases present (within 45 days prior to registration)
- Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing is not required for entry into protocol
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
- The patient must agree to use a highly effective contraception, including men with vasectomies if they are having sex with a woman of childbearing potential or with a woman who is pregnant, while on study drug and for 6 months following the last dose of study drug. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
- The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Exclusion Criteria:
- Patients with planned treatment of all metastatic disease with definitive therapy including either surgery, ablative (non-palliative) doses of radiation, or intervention of some type (definitive interventional radiology techniques) to ALL metastatic sites rendering the patient without extra-renal measurable disease. Patients NOT planned for definitive treatment of all metastatic sites are eligible. Lesions radiated palliatively are not eligible for response assessment
- Patients with untreated or unstable brain metastases or cranial epidural disease
- Note: Patients who have been adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator are eligible. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator
- Prior radiotherapy to the kidney that would result in overlap of radiation therapy fields treatment of the primary tumor
- Any systemic therapy for metastatic renal cell carcinoma (RCC) that was initiated > 90 days before registration, note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration)
- Severe, active comorbidity defined as follows:
- Active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
- History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies
- Active tuberculosis (purified protein derivative [PPD] response without active tuberculosis [TB] is allowed)
- Uncontrolled hypertension (systolic blood pressure [BP] > 190 mmHg or diastolic BP > 110 mmHg)
- Major surgery requiring hospital admission ≤ 28 days prior to registration.
- Any serious (requiring hospital stay or long-term rehab) non-healing wound, ulcer, or bone fracture within 45 days prior to registration
- Any arterial thrombotic (ST elevation myocardial infarction [STEMI], non-ST elevation myocardial infarction [NSTEMI], cerebrovascular accident [CVA], etc) events within 180 days prior to registration
- Active New York (NY) Heart Association class 3-4 heart failure symptoms
- Moderate or severe hepatic impairment (Child-Pugh B or C)
- Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) within 180 days prior to registration. (Any asymptomatic or treated pulmonary embolism or asymptomatic treated deep venous thrombosis > 30 days prior to registration is allowed)
- Unstable cardiac arrhythmia within 180 days prior to registration
- History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to registration
- History of or active inflammatory bowel disease
- Malabsorption syndrome within 45 days prior to registration
- Pregnancy and individuals unwilling to discontinue nursing. For women of child bearing potential must have a negative pregnancy test =< 45 days prior to registration
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.
Video Education with Result Dependent dIsclosure (VERDI)
- NCT05225428
The overall study objective is to identify and evaluate strategies to improve the accessibility of the video education with result dependent disclosure (VERDI) model, increasingly utilized as a pre-genetic testing (pretest) education alternative in clinical practice, to better serve a more diverse patient population at risk for hereditary cancers.
This developmental work is imperative as the VERDI models utilized at DFCI in research studies #18-411 (ProActive), #17-409 (ProGen), #19-068 (OPT-IN), and #19-652 (GeneBOPP) have been overwhelmingly used in DFCI patients of Caucasian ancestry. While DFCI participants have responded well, in an effort improve the generalizability of VERDI and expand it to a diverse patient population, qualitative feedback is being sought explicitly from patients who self-identify as Black and Latinx patients.
A brief qualitative assessment among a small, cohort of English and Spanish speaking Black and Latinx participants will first be conducted to identify refinements to video education (VE) that may increase the utility of the VERDI model for patients in these traditionally underserved populations. Participants in the qualitative assessment study will receive VE exclusively for pretest education, followed by a short interview with research staff regarding their experiences with the VE model. The qualitative assessment study will precede a large-scale randomized controlled trial of VERDI vs standard genetic counseling (SGC), as informed by the results of the developmental study.
We hypothesize that the data yielded from the completion of the study objectives will assist in further refining the VERDI model and its use in clinical practices for the purpose of increasing genetic testing uptake and improving patient outcomes in minority populations that have been underrepresented in similar research to date.
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Protocol Number:
042207
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Principal Investigator:
Deborah L Toppmeyer
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Phase:
N/A
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Scope:
National
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Applicable Disease Sites:
Breast
,Colon
,Kidney
,Melanoma, Skin
,Ovary
,Pancreas
,Prostate
,Soft Tissue
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Read Inclusion & Exclusion Criteria
Inclusion Criteria:
- Age ≥ 18 years
- Current or prior diagnosis of breast cancer, ovarian cancer, pancreatic cancer, prostate cancer, colorectal cancer, renal cancer, melanoma, or sarcoma
- Ability to understand spoken or written English or Spanish in a healthcare context
- Ability to understand and the willingness to sign a written informed consent document
- Black or Latinx (qualitative assessment study only)
Exclusion Criteria:
- Prior cancer genetic testing
- Prior germline genetic testing
- Active hematologic malignancy (e.g. chronic lymphocytic leukemia)
- Currently pregnant
- Currently incarcerated
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.