Clinical Trials /

Hormone Receptor Positive Disease Across Solid Tumor Types: A Phase I Study of Single-Agent Hormone Blockade and Combination Approaches With Targeted Agents to Provide Synergy and Overcome Resistance

NCT01197170

Description:

The goal of this clinical research study to find the highest tolerated dose of anastrozole alone or in combination with either everolimus (Afinitor), sorafenib (Nexavar), erlotinib (Tarceva), fulvestrant (Faslodex), or bevacizumab (Avastin) that can be given to patients with advanced cancer. The safety of these drug combinations will also be studied.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Hormone Receptor Positive Disease Across Solid Tumor Types: A Phase I Study of Single-Agent Hormone Blockade and Combination Approaches With Targeted Agents to Provide Synergy and Overcome Resistance
  • Official Title: Hormone Receptor Positive Disease Across Solid Tumor Types: A Phase I Study of Single-Agent Hormone Blockade and Combination Approaches With Targeted Agents to Provide Synergy and Overcome Resistance

Clinical Trial IDs

  • ORG STUDY ID: 2010-0504
  • SECONDARY ID: NCI-2012-01794
  • NCT ID: NCT01197170

Conditions

  • Solid Tumors
  • Advanced Cancer

Interventions

DrugSynonymsArms
AnastrozoleArimidexAnastrozole
BevacizumabAvastin, Anti-VEGF monoclonal antibody, rhuMAB-VEGFAnastrozole + Bevacizumab
EverolimusAfinitor, RAD001Anastrozole + Everolimus
SorafenibNexavar, BAY43-9006Anastrozole + Sorafenib
ErlotinibOSI-774, TarcevaAnastrozole + Erlotinib

Purpose

The goal of this clinical research study to find the highest tolerated dose of anastrozole alone or in combination with either everolimus (Afinitor), sorafenib (Nexavar), erlotinib (Tarceva), fulvestrant (Faslodex), or bevacizumab (Avastin) that can be given to patients with advanced cancer. The safety of these drug combinations will also be studied.

Detailed Description

      The Study Drugs:

      Anastrozole is designed to block the last step in estrogen (a hormone) production. In
      estrogen-dependent tumors, anastrozole may block tumor growth.

      Sorafenib is designed to block the function of a cancer protein as well as tumor blood-vessel
      forming proteins. It may stop the growth of blood vessels in tumors.

      Bevacizumab is designed to block or slow down the growth of cancer cells by blocking the
      growth of blood vessels that supply nutrients for tumor growth.

      Everolimus is designed to block cancer proteins and may block tumor growth.

      Erlotinib is designed to block the activity of a protein found on the surface of many tumor
      cells that may control tumor growth and survival. This may stop tumors from growing.

      Fulvestrant is designed to block estrogen action. In estrogen-dependent tumors, fulvestrant
      may block tumor growth.

      Study Drug Groups:

      If you are found to be eligible to take part in this study, you will be assigned to a study
      group. The study staff will tell you the group you will be in.

      Anastrozole Alone:

      If you have not received earlier hormonal treatment, you may receive anastrozole alone.

      Anastrozole Combination Groups:

      If you have benefitted from hormonal treatment in the past, you may receive anastrozole
      combined with either bevacizumab, everolimus, sorafenib, or erlotinib.

      If you are receiving treatment with a combination of drugs, you will be assigned to a dose
      level based on when you joined the study. Every group will receive the same dose level of
      anastrozole. The first group of participants will receive the lowest dose level of the second
      study drug (bevacizumab, everolimus, sorafenib, or erlotinib). Each new group will receive a
      higher dose of the second study drug than the group before it, if no intolerable side effects
      were seen. This will continue until the highest tolerable dose of the drug combinations are
      found.

      Once the highest tolerated dose of the drug combinations are found, 10 extra participants
      will be enrolled at this dose level for each combination. This is called the expansion group.

      In addition to this expansion, if a particular tumor type has responded to the study drug(s),
      14 more participants with that tumor type will be enrolled at the highest safe dose level
      that has been found.

      If your tumor starts growing again after an initial response to the combination of 2 drugs, a
      third drug may be added to the combination you have been taking. Depending on your current
      treatment one of the following drugs may be added: bevacizumab, everolimus, sorafenib,
      fulvestrant, or erlotinib.

      Study Drug Administration:

      If you take anastrozole alone or in combination with sorafenib or erlotinib or everolimus,
      each study "cycle" is 28 days. If you take anastrozole in combination with bevacizumab, each
      study "cycle" is 21 days.

      You will take anastrozole by mouth 1 time every day. You can take this with or without food.

      If you are assigned to take sorafenib, you will take it by mouth 1 or 2 times every day. Your
      doctor will tell you how often to take sorafenib. You should take sorafenib on an empty
      stomach either 1 hour before a meal or 2 hours after a meal.

      If you are assigned to take bevacizumab, you will receive it by vein on Day 1 of every cycle.
      During Day 1 of Cycle 1, you will receive it over 90 minutes. The infusion time may be
      lowered if you tolerate the drug well.

      If you are assigned to take everolimus, you will take it by mouth 1 time every day with food.

      If you are assigned to take erlotinib, you will take it by mouth 1 time every day. You should
      take erlotinib on an empty stomach either 1 hour before eating or 2 hours after eating.

      If you are assigned to receive fulvestrant, you will receive injections about one time every
      month. Depending on your study drug combination, you may receive 2 injections in the first
      month.

      For the first Cycle of any of the assigned combinations you will receive the medication at MD
      Anderson. After the first cycle you may receive the medication with your home physician if
      your study doctor feels it is safe.

      Study Visits:

      At every visit, you will be asked if you have had any side effects.

      If you take anastrozole combinations in a 28 day cycle, you will have the following tests and
      procedures:

      During Weeks 1 and 3 of Cycle 1:

        -  You will have a physical exam, including measurement of your weight and vital signs.

        -  Your performance status will be recorded.

        -  Blood (about 1 teaspoon) will be drawn for routine tests.

      During Week 1 of Cycles 2 and beyond:

        -  You will have a physical exam, including measurement of your weight and vital signs.

        -  Your performance status will be recorded.

        -  Blood (about 1 teaspoon) will be drawn for routine tests.

        -  If your study doctor feels it is safe, you may have these follow-up visits with your
           home physician.

      Every 3 cycles, you will have a CT scan, MRI scan, PET scan, and/or PET/CT scan to check the
      status of the disease. If the study doctor thinks more scans are needed, they will be
      performed more often.

      If you take anastrozole combinations in a 21 day cycle, you will have the following tests and
      procedures:

      During Week 1 of Cycle 1:

        -  You will have a physical exam, including measurement of your weight and vital signs.

        -  Your performance status will be recorded.

        -  Blood (about 1 teaspoon) will be drawn for routine tests.

      During Week 1 of Cycle 2 and beyond:

        -  You will have a physical exam, including measurement of your weight and vital signs.

        -  Your performance status will be recorded.

        -  Blood (about 1 teaspoon) will be drawn for routine tests.

        -  If your study doctor feels it is safe, you may have these follow-up visits with your
           home physician.

      Every 3 cycles, you will have a CT scan, MRI scan, PET scan, and/or PET/CT scan to check the
      status of the disease. If the study doctor thinks more scans are needed, they will be
      performed more often.

      Length of Study:

      You may take the study drug(s) for as long as the doctor thinks it is in your best interest.
      You will be taken off study if you have intolerable side effects or the cancer gets worse.

      Your participation on the study will be over once you have completed the end-of-study visit.

      End-of-Study Visit:

      About 30 days after the last dose of study drug(s), you will have an end-of-study visit. At
      this visit, the following tests or procedures may be performed:

        -  You will have a physical exam, including measurement of your weight and vital signs.

        -  Your performance status will be recorded.

        -  Blood (about 2 teaspoons) and urine will be collected for routine tests.

        -  If the doctor thinks it is needed, you will have a CT scan, MRI scan, PET scan, and/or
           PET/CT to check the status of the disease.

      If you have a serious side effect that lasts after the End-of-Study visit, you will be
      followed as long as the doctor thinks it is in your best interest.

      This is an investigational study. Anastrozole, bevacizumab, everolimus, erlotinib, and
      sorafenib are all commercially available. Anastrozole is FDA approved to treat postmenopausal
      women with hormone receptor-positive early breast cancer. Bevacizumab is FDA approved to
      treat non-small cell lung cancer (NSCLC), colorectal cancer, breast cancer, and glioblastoma.
      Everolimus is FDA approved to treat advanced renal cell carcinoma. Sorafenib is FDA approved
      to treat advanced renal cell carcinoma, as well as hepatocellular carcinoma that cannot be
      removed by surgery. Erlotinib is FDA approved to treat NSCLC and pancreatic cancer.
      Fulvestrant is approved to treat breast cancer in postmenopausal women with estrogen receptor
      positive cancer.

      The combination of these drugs is considered investigational.

      Up to 281 patients will take part in this study. All will be enrolled at MD Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
AnastrozoleExperimental1 mg PO (by mouth) daily for 28 days.
  • Anastrozole
Anastrozole + BevacizumabExperimentalAnastrozole 1 mg PO daily and Bevacizumab starting dose 10 mg IV Day 1 of 21 day cycle. Expansion group added when MTD dose of Anastrozole + Bevacizumab found.
  • Anastrozole
  • Bevacizumab
Anastrozole + EverolimusExperimentalAnastrozole 1 mg PO daily and Everolimus starting dose 5 mg PO daily for 28 day cycle. Expansion group added when MTD dose of Anastrozole + Everolimus found.
  • Anastrozole
  • Everolimus
Anastrozole + SorafenibExperimentalAnastrozole 1 mg PO daily and Sorafenib starting dose 200 mg PO twice a day for 28 day cycle. Expansion group added when MTD dose of Anastrozole + Sorafenib found.
  • Anastrozole
  • Sorafenib
Anastrozole + ErlotinibExperimentalAnastrozole 1 mg PO daily and Erlotinib starting dose 75 mg PO daily for 28 day cycle. Expansion group added when MTD dose of Anastrozole + Erlotinib found.
  • Anastrozole
  • Erlotinib

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with pathologically confirmed advanced or metastatic cancer that is
             refractory to standard therapy, relapsed after standard therapy, or who have had no
             standard therapy that induces a CR rate of at least 10% or improves survival by at
             least three months.

          2. Measurable or non-measurable disease

          3. Patients must have tumors that demonstrate ER/PR+ (positivity by IHC staining >/= 1%).

          4. At least 4 weeks since the last dose of chemotherapy, immunotherapy, surgery, or
             radiation therapy (Exception: patients may have received palliative low dose radiation
             therapy one week before treatment provided it is not given to the only targeted
             lesions); at least 6 weeks for therapy which is known to have delayed toxicity
             (nitrosoureas, mitomycin-C, and liposomal doxorubicin); at least 4 weeks (or 5
             half-lives, whichever is shorter) since treatment with biologic/targeted therapies; at
             least 2 weeks since last hormonal therapy

          5. Eastern Cooperative Oncology Group (ECOG) performance status 0,1, or 2

          6. Patients must have normal organ and marrow function defined as: absolute neutrophil
             count >/= 1,000/mL; platelets >/= 50,000/mL; creatinine </= 2 X ULN; total bilirubin
             </= 2.0; ALT(SGPT) </= 3 X ULN; Exception for patients with liver metastasis: total
             bilirubin </= 3 x ULN; ALT(SGPT) </= 5 X ULN.

          7. Women of childbearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry, for
             the duration of study participation, and for 30 days after the last dose.

          8. Ability to understand and the willingness to sign a written informed consent document

          9. Female patients must either be: Post-menopausal women as defined by a. age >/= 60
             years of age; b. prior bilateral oophorectomy; c. age < 60 with at least 12 months of
             spontaneous amenorrhea or post-menopausal range FSH and estradiol levels OR
             Premenopausal women receiving a gonadotropin-releasing hormone agonist.

        Exclusion Criteria:

          1. Patients with uncontrolled concurrent illness, including but not limited to: ongoing
             or active infection; altered mental status or psychiatric illness/social situations
             that would limit compliance with study requirements and/or obscure study results.

          2. Uncontrolled systemic vascular hypertension (systolic blood pressure > 140 mm Hg,
             diastolic blood pressure > 90 mm Hg on medication).

          3. Patients with clinically significant cardiovascular disease: history of CVA within 6
             months, myocardial infarction or unstable angina within 6 months, or unstable angina
             pectoris.

          4. Women who are pregnant or breastfeeding

          5. Patients with a history of bone marrow transplant within the previous two years.

          6. Patients with a known hypersensitivity to any of the components of the drug products.

          7. Patients unable to swallow oral medications or with pre-existing gastrointestinal
             disorders that might interfere with proper absorption of oral drugs.

          8. Patients with major surgery within 30 days prior to entering the study.

          9. Age under 18 years.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD)
Time Frame:28 day cycle
Safety Issue:
Description:MTD defined as highest dose at which no more than 1 of 6 evaluable patients has had a dose limiting toxicity (DLT). Six patients should be treated before the dose is declared as MTD. DLTs defined as adverse events (AEs) related to study agents which occurs during the first cycle of treatment.

Secondary Outcome Measures

Measure:Tumor Response
Time Frame:Every 21 or 28 days depending on study group
Safety Issue:
Description:Tumor response defined as one or more of the following: (1) stable disease for more than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by RECIST criteria, (3) decrease in tumor markers by more than or equal to 25% (for example, a ≥ 25% decrease in CA125 for patients with ovarian cancer), or (4) a partial response according to the Choi criteria, i.e. decrease in size by 10% or more, or a decrease in the tumor density, as measured in Hounsfield units (HU), by more than or equal to 15%.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Hormonal therapies
  • Estrogen receptor
  • Progesterone receptor
  • Hormone blockade
  • Hormone-positive tumors
  • Advanced cancer
  • Metastatic cancer
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAB-VEGF
  • Afinitor
  • RAD001
  • Nexavar
  • BAY43-9006
  • OSI-774
  • Tarceva

Last Updated