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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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Solid Tumors, Advanced Cancer

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Trial Information

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


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, anastrozole
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.

If you agree, your leftover tumor tissue sample will be stored in an internal research
tissue bank at MD Anderson for use in future research related to cancer.

Before your tissue can be used for research, the people doing the research must get specific
approval from the Institutional Review Board (IRB) of MD Anderson. The IRB is a committee
made up of doctors, researchers, and members of the community. The IRB is responsible for
protecting the participants involved in research studies and making sure all research is
done in a safe and ethical manner. All research done at MD Anderson, including research
involving your tissue from this bank, must first be approved by the IRB.

Your samples will be given a code number. No identifying information will be directly
linked to your samples. Only the researcher in charge of the bank will have access to the
code numbers and be able to link the samples to you. This is to allow medical data related
to the samples to be updated as needed. Other researchers using your samples will not be
able to link this data to you.

Up to 190 patients will take part in this study. All will be enrolled at MD Anderson.


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 bilirubin
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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome Time Frame:

Every 28 day cycle

Safety Issue:

Yes

Principal Investigator

Jennifer J. Wheler, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2010-0504

NCT ID:

NCT01197170

Start Date:

September 2010

Completion Date:

Related Keywords:

  • Solid Tumors
  • Advanced Cancer
  • 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
  • Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030