Trial Search Results

Testing the Addition of the Pill Chemotherapy, Cabozantinib, to the Standard Immune Therapy Nivolumab Compared to Standard Chemotherapy for Non-small Cell Lung Cancer

This phase II trial compares cabozantinib alone and the combination of cabozantinib and nivolumab to standard chemotherapy in the treatment of patients with non-squamous non-small cell lung cancer (NSCLC). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ramucirumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as docetaxel, gemcitabine hydrochloride, paclitaxel, and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving cabozantinib alone or in combination with nivolumab may be more effective than standard chemotherapy in treating patients with non-small cell lung cancer.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Drug: Cabozantinib S-malate
  • Drug: Docetaxel
  • Drug: Gemcitabine Hydrochloride
  • Drug: Nab-paclitaxel
  • Biological: Nivolumab
  • Drug: Paclitaxel
  • Biological: Ramucirumab

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - ELIGIBILITY CRITERIA FOR STEP 0 (PRE-REGISTRATION): Patient must have pathologically
   confirmed non-squamous non-small cell lung carcinoma (NSCLC)

   - ELIGIBILITY CRITERIA FOR STEP 0 (PRE-REGISTRATION): Patient must have stage IV disease
   (includes M1a, M1b, or recurrent earlier stage disease), according to the 8th edition
   of the lung cancer Tumor Node Metastasis (TNM) classification system

   - ELIGIBILITY CRITERIA FOR STEP 0 (PRE-REGISTRATION): Patient must have predominant
   non-squamous histology (patients with NSCLC no otherwise specified [NOS] are
   eligible). Mixed tumors will be categorized by the predominant cell type. If small
   cell elements are present the patient is ineligible

   - ELIGIBILITY CRITERIA FOR STEP 0 (PRE-REGISTRATION): Patient's tumor(s) must be tested
   and known negative for EGFR tyrosinase kinase inhibitor (TKI) sensitizing mutations
   (EGFR Exon 19 deletions, L858R, L861Q, G719X) and ALK gene rearrangements (by
   fluorescence in situ hybridization [FISH], next generation sequencing [NGS], or
   immunohistochemistry [IHC]) by routine Clinical Laboratory Improvement Act
   (CLIA)-certified clinical testing methods. Negative circulating tumor deoxyribonucleic
   acid (DNA) results alone are not acceptable. Prior testing for tumor PD-L1 status is
   not required

   - ELIGIBILITY CRITERIA FOR STEP 0 (PRE-REGISTRATION): Patients WITHOUT tumors with known
   molecular alterations in ROS1, MET, RET, or must have progressed radiographically (per
   local investigator assessment) following one, but only one, line of platinum-based
   chemotherapy AND one, but only one, line of prior immunotherapy. Lines of therapy are
   defined by clinical or radiographic progression. Patients may have received
   chemotherapy and immunotherapy either concurrently or sequentially in either order.
   Patient must have received at least 2 prior doses of checkpoint inhibitor therapy in
   an every 2, 3, or 4 week schedule. No submission of molecular testing is required and
   patients may be registered for Step 0 then proceed directly to Step 1 screening OR
   Patients with tumors with known molecular alterations in ROS1, MET, and RET must have
   progressed radiographically (per local investigator clinical assessment) on at least
   one line of prior chemotherapy or targeted therapy, but there is no limit on number of
   prior number. Reciept of prior immunotherapy is allowed but not required.

      - Known molecular alterations in ROS1 , MET, and RET are defined as below ROS1 gene
      rearrangement by FISH or DNA analysis. In addition to above requirements, these
      patients must have progressed on at least one prior ROS1 TKI therapy

      - MET exon 14 splice mutations on DNA analysis. In addition to above requirements,
      prior MET directed TKI therapy is optional

      - MET mutations predicted to be sensitive to MET inhibitor. In addition to above
      requirements, prior MET directed TKI therapy is optional

      - High MET amplification by FISH (characterized by a fluorescence in situ
      hybridization MET/CEP7 ratio of 5 or greater); OR MET amplification by DNA NGS
      CLIA certified assay. In addition to above requirements, prior MET directed TKI
      therapy is optional

      - RET gene rearrangement by FISH or DNA analysis. In addition to above
      requirements, prior RET directed TKI therapy is optional

         - During Step 0 screening, CLIA reports of the testing results must be
         submitted via Medidata Rave for central review for instructions. The central
         review will be performed by the study chair, co-chair, biology co-chair,
         and/or a delegate to determine that the results indicate a patient's
         eligibility for targeted therapy. CLIA reports that contain information
         pertaining to any of the above mutations will be uploaded to Medidata Rave
         for central review of documentation for determination of patient eligibility
         for targeted therapy (Arm T). Central testing of tissue will not be
         performed. Institutions will be notified of the patient's eligibility status
         for Arm T within two (2) business days of submission of the molecular
         testing reports. Patients with tumors with the above known molecular
         alterations are eligible for cohort Arm Z following Step 1 eligibility
         review. Patients without tumors with the above known molecular alterations
         for randomization to Arm A, B or C following Step 1 eligibility review

   - ELIGIBILITY CRITERIA FOR STEP 0 (PRE-REGISTRATION): NOTE: 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 (in
   the opinion of the treating physician) are eligible for this trial

   - ELIGIBILITY CRITERIA FOR STEP 0 (PRE-REGISTRATION): Patients with known history or
   current symptoms of cardiac disease, or history of treatment with cardiotoxic agents
   (such as anthracycline or human epidermal growth factor receptor (HER2)-directed
   antibody therapy, but not prior checkpoint inhibitor therapy), must have a clinical
   risk assessment of cardiac function using the New York Heart Association functional
   classification. To be eligible for this trial, patients must be class 2B or better

   - ELIGIBILITY CRITERIA FOR STEP 0 (PRE-REGISTRATION): Patient must have Eastern
   Cooperative Oncology Group (ECOG) performance status 0-1

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Patient must have met the eligibility criteria outlined above

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Patient must have measurable disease as defined by RECIST version (v) 1.1 criteria.
   Measurements must be obtained within 4 weeks prior to randomization/registration

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Patient must have an anticipated life expectancy greater than 3 months

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Any prior chemotherapy (based on administration schedule) must have been completed in
   greater than or equal to the following times prior to randomization/registration:

      - Chemotherapy/targeted oral therapy administered in a daily or weekly schedule
      must be completed >= 1 week prior to randomization/registration

      - Any chemotherapy administered in an every 2 week or greater schedule must be
      completed >= 2 weeks prior to randomization/registration

      - Additionally, patient should be recovered to equal to or less than grade 1
      toxicities related to any prior treatment, unless adverse events (AE[s]) are
      clinically non significant and/or stable on supportive therapy (as determined by
      the treating physician)

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Leukocytes >= 3,000/mcL (obtained within 2 weeks prior to randomization/registration)

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Absolute neutrophil count >= 1,500/mcL (obtained within 2 weeks prior to
   randomization/registration)

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Platelets >= 100,000/mcL (obtained within 2 weeks prior to randomization/registration)

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Hemoglobin >= 9 g/dL (obtained within 2 weeks prior to randomization/registration)

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (obtained within 2
   weeks prior to randomization/registration)

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
   alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
   ULN (obtained within 2 weeks prior to randomization/registration)

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Creatinine =< 1.5 x ULN OR calculated (Cockcroft-Gault formula) or measured creatinine
   clearance >= 50 mL/min/1.73 m^2 (normalized to body surface area [BSA]) for patients
   with creatinine levels greater than 1.5 times the institutional normal creatinine =<
   1.5 x ULN or creatinine clearance >= 50 ml/min/1.73 m^2 (obtained within 2 weeks prior
   to randomization/registration)

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Patient must have corrected QT interval calculated by the Fridericia formula QTc
   corrected by Fridericia (QTcF) =< 500 ms within 28 days prior to
   randomization/registration

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Patient must be able to swallow tablets

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Patients with treated brain metastases are eligible if follow-up brain imaging after
   central nervous system (CNS)-directed therapy shows no evidence of progression

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Patients with new or progressive brain metastases (active brain metastases) are
   eligible if the treating physician determines that immediate CNS specific treatment is
   not required and is unlikely to be required during the first cycle of study treatment.

      - Patient must meet one of the following criteria with respect to brain metastases:
      Patients with no known brain metastasis must have baseline brain imaging within
      12 weeks prior to study randomization/registration not demonstrating brain
      metastases OR patients with known brain metastases must have baseline brain
      imaging and completed treatment to all symptomatic brain metastases (with whole
      brain radiation or radiosurgery; or complete neurosurgical resection >= 3 months
      prior to randomization/registration) >= 4 weeks prior to
      randomization/registration. They must be clinically stable. Known leptomeningeal
      disease is not allowed

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Known human immunodeficiency virus (HIV)-infected patients on effective
   anti-retroviral therapy with undetectable viral load within 6 months of registration
   are eligible for this trial

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   For patients with known history of chronic hepatitis B virus (HBV) infection, the HBV
   viral load must be undetectable on suppressive therapy at time of
   registration/randomization, if indicated

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Patients with a known history of hepatitis C virus (HCV) infection must have been
   treated and cured. For patients with HCV infection who are currently on treatment,
   they are eligible if they have an undetectable HCV viral load at time of
   registration/randomization

   - ADDITIONAL ELIGIBILITY CRITERIA FOR STEP 1 (REGISTRATION) TARGETED ARM T: Patient was
   registered to step 0, targeted arm and central review results report the patient is
   eligible for arm T

   - ADDITIONAL ELIGIBILITY CRITERIA FOR STEP 1 (REGISTRATION) TARGETED ARM T: Patients
   with ROS1 gene rearrangements must have progressed on at least one prior ROS1 targeted
   therapy such as crizotinib

   - ADDITIONAL ELIGIBILITY CRITERIA FOR STEP 1 (REGISTRATION) TARGETED ARM T: Patient must
   have progressed radiographically (per local investigator clinical assessment) on at
   least one line of prior chemotherapy or targeted therapy, but there is no limit on
   number of prior number. Prior immunotherapy is allowed but not required. Prior
   bevacizumab with chemo is allowed.

      - NOTE: The requirement for prior chemotherapy will be met if patients have
      recurrence within 6 months after prior adjuvant platinum based chemotherapy for
      early stage disease, or recurrence within 6 months after prior radiotherapy plus
      platinum based chemotherapy for locally advanced disease

      - NOTE: Patients with unresectable stage III NSCLC who have received chemo and
      radiation then consolidation durvalumab, followed by progression are eligible if
      progression happens after > 2 doses of durvalumab. Prior bevacizumab with chemo
      is also allowed

   - STEP 2 ELIGIBILITY CRITERIA (CROSSOVER ARM Z): Patients must have met all eligibility
   requirements for Step 1 at time of registration to Step 1 to be eligible for Step 2

   - STEP 2 ELIGIBILITY CRITERIA (CROSSOVER ARM Z): Patients must have radiographic
   progressive disease per RECIST criteria after >= 2 cycles of therapy on arm C

   - STEP 2 ELIGIBILITY CRITERIA (CROSSOVER ARM Z): Patients must be registered to step 2
   within 4 weeks of the last dose of treatment administration from step 1

   - STEP 2 ELIGIBILITY CRITERIA (CROSSOVER ARM Z): Patients must have an ECOG performance
   status between 0-2

   - STEP 2 ELIGIBILITY CRITERIA (CROSSOVER ARM Z): Patients must have recovered to
   baseline (pre-step 1) or Common Terminology Criteria for Adverse Events (CTCAE) v.5.0
   =< grade 1 from toxicity due to all prior therapies except alopecia and other
   non-clinically significant adverse events (AEs)

   - STEP 2 ELIGIBILITY CRITERIA (CROSSOVER ARM Z): Leukocytes >= 3,000/mcL (obtained
   within 2 weeks prior to randomization/registration)

   - STEP 2 ELIGIBILITY CRITERIA (CROSSOVER ARM Z): Absolute neutrophil count >= 1,500/mcL
   (obtained within 2 weeks prior to randomization/registration)

   - STEP 2 ELIGIBILITY CRITERIA (CROSSOVER ARM Z): Platelets >= 100,000/mcL (obtained
   within 2 weeks prior to randomization/registration)

   - STEP 2 ELIGIBILITY CRITERIA (CROSSOVER ARM Z): Hemoglobin >= 9 g/dL (obtained within 2
   weeks prior to randomization/registration)

   - Total bilirubin =< 1.5 x institutional ULN (obtained within 2 weeks prior to
   randomization/registration)

   - STEP 2 ELIGIBILITY CRITERIA (CROSSOVER ARM Z): Aspartate aminotransferase (AST) (serum
   glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum
   glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (obtained within 2 weeks prior to
   randomization/registration)

   - STEP 2 ELIGIBILITY CRITERIA (CROSSOVER ARM Z): Creatinine =< 1.5 x ULN OR calculated
   (Cockcroft-Gault formula) or measured creatinine clearance >= 50 mL/min/1.73 m^2
   (normalized to BSA) for patients with creatinine levels greater than 1.5 times the
   institutional normal creatinine =< 1.5 x ULN or creatinine clearance >= 50 ml/min/1.73
   m^2 (obtained within 2 weeks prior to randomization/registration)

   - STEP 2 ELIGIBILITY CRITERIA (CROSSOVER ARM Z): Patients must have corrected QT
   interval calculated by the Fridericia formula (QTcF) =< 500 ms within 28 days before
   registration

Exclusion Criteria:

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Patient must not have had any prior radiation therapy for bone metastasis within 2
   weeks, or any other radiation therapy within 4 weeks prior to
   randomization/registration

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Women must not be pregnant or breast-feeding due to the unknown effects of
   cabozantinib and nivolumab on human development and for the potential risk for adverse
   events in nursing infants with the treatment regimens being used. All females of
   childbearing potential must have a blood test or urine study within 14 days prior to
   randomization/registration to rule out pregnancy. A female of childbearing potential
   is any woman, regardless of sexual orientation or whether they have undergone tubal
   ligation, who meets the following criteria:

      - Has achieved menarche at some point,

      - Has not undergone a hysterectomy or bilateral oophorectomy;

      - Has not been naturally postmenopausal (amenorrhea following cancer therapy does
      not rule out childbearing potential) for at least 24 consecutive months (i.e.,
      has had menses at any time in the preceding 24 consecutive months).

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Women of childbearing potential and sexually active males must not expect to conceive
   or father children by using accepted and effective method(s) of contraception or by
   abstaining from sexual intercourse for the duration of their participation in the
   study and for up to 7 months after completion of treatment on the study

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Clinically significant gastrointestinal bleeding within 6 months prior to
   randomization/registration

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Pulmonary hemorrhage or hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3
   months prior to randomization/registration

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Any grade drug induced pneumonitis within 3 months prior to
   randomization/registration. Prior immune mediated pneumonitis of grade 3 or 4 are not
   eligible regardless of time window

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Current radiographic evidence of cavitating pulmonary lesion(s)

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Current radiographic evidence of tumor invading any major blood vessels

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small
   or large bowel, rectum or anus), or any evidence of endotracheal or mainstem
   endobronchial tumor within 28 days prior to randomization/registration

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Peptic ulcer disease, inflammatory bowel, known malabsorption syndrome, bowel
   obstruction or gastric outlet obstruction (percutaneous endoscopic gastrostomy [PEG]
   tube placement) within 3 months prior to randomization/registration

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Abdominal fistula, GI perforation, intra-abdominal abscess within 6 months prior to
   randomization/registration

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Grade 3 or greater infection, or infection requiring intravenous systemic treatment
   within 28 days prior to randomization/registration. Patients should be off antibiotics
   at the time of randomization/registration

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Serious non-healing wound/ulcer/bone fracture within 28 days prior to
   randomization/registration

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   History of organ transplant

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Concurrent symptomatic untreated hypothyroidism within 7 days prior to
   randomization/registration

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   History of major surgery (within 3 months, with wound healing within 28 days, prior to
   randomization/registration), minor surgery (within 28 days prior to
   randomization/registration), other minor procedures (within 7 days prior to
   randomization/registration) or clinically relevant ongoing complications from prior
   surgery

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm
   Hg systolic, or > 90 mm Hg diastolic within 7 days of registration despite optimal
   antihypertensive treatment

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Unstable angina pectoris (within 6 months prior to therapy)

   - ELIGIBILITY CRITERIA FOR STEP 1 (RANDOMIZATION/REGISTRATION) FOR ALL TREATMENT ARMS:
   Clinically-significant cardiac arrhythmias (within 6 months prior to therapy)

   - ELIGI

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Martina Steffen
650.721.3572
Recruiting