Personalized Targeted Inhibitors Treatment in Renal Cell Cancer
| Status: | Terminated |
|---|---|
| Conditions: | Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 10/14/2018 |
| Start Date: | January 4, 2016 |
| End Date: | July 27, 2017 |
Targeting of Renal Cell Cancer With Specific Inhibitors: A Model for Selective Adaptive Medicine Based on Molecular Alterations
This is for subjects with metastatic Renal Cell Cancer (RCC). There are four Food and Drug
Administration (FDA) approved drugs for first-line therapy of Renal Cell Cancer (RCC) and two
for second-line therapy. Each of these drugs targets a specific molecular pathway. At present
oncologists select therapy based on current guidelines. There is a new method for trying to
use biomarker information from the subject's tumor to select the best drug to treat the
subject. This process is investigational, which is why this study is being done.
Biomarkers are genes, proteins and other molecules that affect how cancer cells grow,
multiply, die and respond to other compounds in the body. These biomarkers build a tumor
profile or "fingerprint" of the subject's tumor. A new focus in cancer care is personalized
treatment, where doctors select a drug based on the subject's tumor's unique "fingerprint"
which is more likely to be effective in fighting the tumor. Selecting the treatment the
subject is more likely to respond to requires a thorough understanding of the relationship
between biomarker and treatment effect. The PI wants to gather data to understand that
relationship to help treat future cancer patients. The purpose of this study is to evaluate
efficacy of treatments that are selected based on tumor profiles.
Administration (FDA) approved drugs for first-line therapy of Renal Cell Cancer (RCC) and two
for second-line therapy. Each of these drugs targets a specific molecular pathway. At present
oncologists select therapy based on current guidelines. There is a new method for trying to
use biomarker information from the subject's tumor to select the best drug to treat the
subject. This process is investigational, which is why this study is being done.
Biomarkers are genes, proteins and other molecules that affect how cancer cells grow,
multiply, die and respond to other compounds in the body. These biomarkers build a tumor
profile or "fingerprint" of the subject's tumor. A new focus in cancer care is personalized
treatment, where doctors select a drug based on the subject's tumor's unique "fingerprint"
which is more likely to be effective in fighting the tumor. Selecting the treatment the
subject is more likely to respond to requires a thorough understanding of the relationship
between biomarker and treatment effect. The PI wants to gather data to understand that
relationship to help treat future cancer patients. The purpose of this study is to evaluate
efficacy of treatments that are selected based on tumor profiles.
This will be a prospective, one-arm, proof of concept study designed to evaluate the efficacy
of algorithm-based allocation (based on genomic/proteomic profile) of first-line therapy in
renal cell carcinoma (RCC).
After eligibility review, patients will receive one of the four first-line therapy agents
based on their tumor's molecular profile as determined using fresh biopsy tissue from an
accessible metastatic site. Upon disease progression, patients will then receive one of two
second-line agents based on their tumor's molecular profile.
Because this is a proof-of-concept study, the sample size is based on feasibility of accrual.
The clinic should be able to recruit 100 patients within a reasonable timeframe for the
study. The number of patients receiving each drug will vary based on the frequency of
molecular alterations in the population. Therefore, groups will not be compared with one
another - the research goal is to determine whether the progression-free survival (PFS) for
each drug is improved over the PFS reported in FDA approval trials for each drug when they
are assigned based on molecular analysis.
of algorithm-based allocation (based on genomic/proteomic profile) of first-line therapy in
renal cell carcinoma (RCC).
After eligibility review, patients will receive one of the four first-line therapy agents
based on their tumor's molecular profile as determined using fresh biopsy tissue from an
accessible metastatic site. Upon disease progression, patients will then receive one of two
second-line agents based on their tumor's molecular profile.
Because this is a proof-of-concept study, the sample size is based on feasibility of accrual.
The clinic should be able to recruit 100 patients within a reasonable timeframe for the
study. The number of patients receiving each drug will vary based on the frequency of
molecular alterations in the population. Therefore, groups will not be compared with one
another - the research goal is to determine whether the progression-free survival (PFS) for
each drug is improved over the PFS reported in FDA approval trials for each drug when they
are assigned based on molecular analysis.
Inclusion Criteria:
- Subjects may be included in the study only if they meet all of the following inclusion
criteria:
- Pathologically confirmed renal cell carcinoma.
- No prior systemic and/or investigative therapy of any kind.
- Patients with primary tumor in place are strongly encouraged to undergo
nephrectomy prior to initiation of study agent.
- Prior palliative radiotherapy to metastatic lesion(s) is permitted. Patient
must have adequately recovered from the acute toxicities of this treatment.
- All major surgery of any type and/or radiotherapy must be completed at least
4 weeks prior to registration.
- Must have progressive metastatic disease
- ECOG performance status ≤2
- Women of childbearing potential and male patients must use acceptable methods of
contraception—tubal ligation, vasectomy, barrier contraceptive with
spermicide—while on study and for 3 months after the last dose of study therapy.
Oral, implantable, or injectable contraceptives may be affected by cytochrome
P450 interactions, and are therefore not considered effective for this study.
- Age ≥18 years
- Required Initial Laboratory Values:
- Granulocytes ≥1,500/µL
- Platelet Count ≥100,000/µL
- Hemoglobin ≥9 g/dL
- AST/ALT ≤ 2.5 times the upper limit of normal (ULN)
- Alk. Phos.≤ 2.5 x ULN
- Serum bilirubin ≤ 1.5 x ULN
- Amylase/Lipase within normal range
- Urinalysis≤ 1+ protein
- T3T4 TSH - within normal range
- Pregnancy test for women - Negative
- Serum creatinine ≤ 1.5 x ULN
- Electrocardiogram (ECG) - no active ischemia
- Echocardiogram ejection fraction ≥40%
- Pulmonary function tests
- Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting
triglycerides ≤2.5 x ULN. NOTE: In case one or both of these thresholds are
exceeded, the patient can only be included after initiation of appropriate
lipid lowering medication.
- Signed informed consent prior to the performance of any study-specific procedures
Exclusion Criteria:
- Ongoing hemoptysis, or cerebrovascular accident within 12 months prior to study entry,
or peripheral vascular disease with claudication occurring upon walking less than one
city block, or history of clinically significant bleeding.
- Deep venous thrombosis or pulmonary embolus within 12 months prior to study entry and
no ongoing need for full-dose oral or parenteral anticoagulation. For maintenance of
catheter patency daily prophylactic aspirin or low-dose coumadin (1-2 mg) is allowed.
- Evidence of current central nervous system (CNS) metastases. All patients must undergo
a CT scan of the brain (with contrast, if possible) within 42 days prior to
registration. Any imaging abnormality indicative of active CNS metastases will exclude
the patient from the study.
- Significant cardiovascular disease defined as congestive heart failure (New York Heart
Association Class II, II or IV) angina pectoris requiring nitrate therapy, or recent
myocardial infarction (within the preceding 6 months prior to study entry).
- Uncontrolled hypertension (defined as blood pressure of ≥160 mmHg systolic and/or ≥90
mmHg diastolic on medication). Document over 48 hours with minimum of 3 readings.
- Ongoing requirement for systemic corticosteroid therapy (except replacement therapy
for adrenal insufficiency) or other immunosuppressants are not permitted. Topical
and/or inhaled steroids are allowed.
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