A Phase 1B/2 Study of LY2940680 in Combination With Weekly Paclitaxel, Carboplatin, and Radiation in Localized Adenocarcinoma of the Esophagus or Gastroesophageal Junction
Information source: M.D. Anderson Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Esophageal Cancer
Intervention: LY2940680 (Drug); Paclitaxel (Drug); Carboplatin (Drug); Radiation Therapy (Radiation); Endoscopy (Procedure)
Phase: Phase 1/Phase 2
Status: Not yet recruiting
Sponsored by: M.D. Anderson Cancer Center Official(s) and/or principal investigator(s): Jaffer Ajani, MD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center
Overall contact: Jaffer Ajani, MD, Phone: 713-792-2828
Summary
The goal of Phase 1B of this clinical research study is to find a dose of LY2940680 that can
be given safely with the chemotherapy drugs carboplatin and paclitaxel and radiotherapy to
patients with esophageal or gastroesophageal junction cancer.
The goal of Phase 2 of this clinical research study is to learn if LY2940680 given with
chemoradiation can help to control the disease. The safety of this treatment combination
will continue to be studied.
Clinical Details
Official title: A Phase 1B/2 Study of LY2940680 in Combination With Weekly Paclitaxel, Carboplatin, and Radiation in Localized Adenocarcinoma of the Esophagus or Gastroesophageal Junction
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Toxicity of LY2940680 with Paclitaxel, Carboplatin and Radiation TherapyPathologic Complete Response (pathCR)
Secondary outcome: Biomarker Expression Levels
Detailed description:
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study
group (Phase 1B or Phase 2) based on when you join this study.
If you are in Phase 1B, the dose of LY2940680 that you will receive is based on when you
join the study. Up to 2 doses of LY2940680 will be tested. Up to 6 participants will be
enrolled at each dose level. Your study doctor will tell you what dose of study drug you
will receive and how this compares to the dose other participants have received.
If you are in Phase 2, you will receive the dose of LY2940680 found to be tolerable in Phase
1B.
Study Treatment:
Phase IB:
You will start LY2940680 on the same day you begin chemoradiation. You will take LY2940680
every day until you complete chemoradiation.
Phase 2:
If you are one of the first 27 participants enrolled in Phase 2, you will take LY2940680 for
7 days before you begin chemoradiation. If you join the study after 27 participants have
been enrolled, you will start LY2940680 on the same day you begin chemoradiation. You will
continue to take LY2940680 every day until you complete chemoradiation.
Phase 1B and Phase 2:
You will take LY2940680 1 time a day by mouth in the morning. You may take LY2940680 with or
without food. Each capsule should be taken at about the same time each morning. If you
forget to take a dose, you should skip that dose and take the next dose on schedule. You
will not need to make up missed doses. You will be asked to record all doses and the time
taken in a drug diary. You will be asked to bring the diary, along with unused capsules and
pill bottles, to each study visit.
You will receive radiation every weekday for 5 ½ weeks. Once a week during this time, you
also will receive paclitaxel by vein over about 3 hours followed by carboplatin by vein over
about 2 hours.
Study Visits:
Every week during treatment with LY2940680 and chemoradiation, blood (about 3 tablespoons)
will be drawn for routine tests.
If you can become pregnant, blood (about 1 teaspoon) will be drawn for a pregnancy test
every 2-4 weeks during treatment.
If you are enrolled in Phase 1B, every week you will have a physical exam.
If you are enrolled in Phase 2:
- Every 2 weeks you will have a physical exam.
- You will have an endoscopy with ultrasound and biopsy performed about 8 days after your
first dose of LY2940680 for biomarker testing.
Tests Before Surgery:
Five (5) to 6 weeks after completion of LY2940680 and chemoradiation, you will have testing
to check the status of the disease and to help your doctor decide if you should have
surgery:
- You will have a physical exam.
- You will have a CT or PET/CT scan.
- Blood (about 3 tablespoons) will be drawn for routine tests.
- You will have an endoscopy with ultrasound and biopsy.
If the tests show you can have surgery, you will sign a standard consent form for the
surgery.
Some of the tissue collected during your surgery will be used for biomarker testing.
If you are not able to have surgery, you will be taken off study.
Length of Treatment:
Your treatment on this study will be over once you finish LY2940680, chemoradiation and
surgery, or LY2940680 and chemoradiation alone if you do not have surgery. You will no
longer be able to take the treatment if the disease gets worse, if intolerable side effects
occur, or if you are unable to follow study directions.
Your participation on the study will be over after the follow-up visits.
Follow-Up after Surgery:
About 3 months after surgery:
- You will have a physical exam.
- You will have an endoscopy, ultrasound (if needed), and biopsy performed.
- Blood (about 3 tablespoons) will be drawn for routine tests.
- If your doctor thinks it is needed, you will have a PET/CT or CT scan.
After Month 3, every 3-6 months for the first year after surgery:
- You will have a physical exam.
- Blood (about 3 tablespoons) will be drawn for routine tests.
- You will have a PET/CT or CT scan to check the status of the disease.
Every 6 months during Years 2 and 3:
- You will have a physical exam.
- Blood (about 3 tablespoons) will be drawn for routine tests.
- You will have a PET/CT or CT scan to check the status of the disease.
- If your doctor thinks it is needed, you will have an endoscopy with ultrasound and
biopsy.
At Years 4 and 5:
- You will have a physical exam.
- Blood (about 3 tablespoons) will be drawn for routine tests.
- You will have a PET/CT or CT scan to check the status of the disease.
Once study treatment is completed, the study staff will continue to follow how you are doing
for up to 5 years. If you stop coming to MD Anderson, you will be contacted by phone every 3
months. The phone call should last about 5 minutes.
This is an investigational study. LY2940680 is not FDA approved or commercially available.
It is currently being used for research purposes only. The study doctor can explain how
the study drug is designed to work. The combination of carboplatin, paclitaxel, and
radiation is a standard treatment for cancer of the esophagus and gastroesophageal junction.
Up to 66 participants will be enrolled in this study. All will be enrolled at MD Anderson.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Histologically or cytologically confirmed adenocarcinoma of the esophagus or
gastroesophageal junction (EAC).
2. Male or female patients whose age is greater than or equal to 18 years (Because
nonclinical studies suggest that LY2940680 may adversely affect the development and
maintenance of teeth, bones, and growth plates in a pediatric population, children
are excluded from this study. In addition, EAC is extremely rare in children).
3. Localized EAC and its baseline clinical stage determined as: T2-T3N0 or T1-3N+.
Imaging studies suspicious for metastases must be followed with a negative biopsy
before a patient can enter the study.
4. Patients with malignant celiac nodes are eligible if the primary lesion is in the
mid-thoracic or distal thoracic esophagus or it is involving the gastroesophageal
junction.
5. Tumor must have labeling index of greater than or equal to 5% of the nuclear Gli-1
(integral biomarker performed in the MD Anderson Cancer Center CLIA laboratory) for
patient to be eligible in this trial (if enough archival tissue is not available to
determine labeling index, patient must agree to a biopsy to be eligible for the
study).
6. Tumor may not extend greater than 4 cm below the gastroesophageal junction.
7. ECOG performance status 0 or 1.
8. Able to swallow capsules.
9. All patients must be willing to provide research tumor tissue for biomarker studies
at baseline (from archival tumor tissue or through endoscopy if sufficient archival
tissue is not available). All patients must also allow biomarker studies on the
tissue obtained through surgery to remove the primary cancer.
10. Phase II only: Patients volunteering for the Phase II part of the protocol must be
willing to undergo a research endoscopy for tissue collection on day 8 (+/- 2 days)
from the beginning of therapy.
11. Absolute neutrophil count greater than or equal to 1500/mm^3; Platelets greater than
or equal to 100,000/mm^3; Hemoglobin greater than or equal to 8 g/dL; Serum
creatinine less than or equal to 2 x Upper Limit of Normal (ULN); ALT and AST less
than or equal to 2. 5 x ULN; Serum bilirubin less than or equal to 1. 5 x ULN.
12. Patient must be able to comprehend the approved consent document and have the
willingness to sign it. The patient prior to enrollment and the administration of any
protocol-specific therapy must sign the consent document.
13. Willingness and ability to comply with study procedures and follow-up examinations.
14. Must be considered medically fit for operation as determined by multidisciplinary
evaluation.
15. Effects of LY2940680 on the developing human fetus at the recommended therapeutic
dose are unknown. For this reason and because Hh signal pathway inhibitors as well as
other therapeutic agents used in this trial are known to be teratogenic, males and
females with reproductive potential must agree to use two forms of medically approved
contraceptive precautions and for at least 6 months following the last dose of
biochemoradiation. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately.
16. (# 15 continued) Women of childbearing potential are defined as follows: Having
regular menstrual cycles; Has amenorrhea, irregular menstrual cycles or using a
contraceptive method that precludes withdrawal bleeding; Have had a tubal ligation.
Women are considered not to be of childbearing potential for the following reasons:
Had hysterectomy and/or bilateral oophorectomy; Post-menopausal defined by amenorrhea
for at least 1 year in a woman >45 years old.
17. Females with childbearing potential must have a negative serum pregnancy test within
14 days prior to treatment start.
Exclusion Criteria:
1. Baseline clinical stage of T1N0 or inoperable T4 (unequivocal organ involvement) are
to be excluded.
2. Unequivocal metastatic tumor at baseline.
3. Tracheo-esophageal (TE) fistula or direct invasion into the tracheo-bronchial mucosa.
A bronchoscopy (biopsy and cytology should be performed) is required to exclude TE
fistula or tracheo-bronchial involvement in patients with a tumor located at <26 cm
from the incisors.
4. Cervical esophageal cancer will not be entered in this study.
5. Any prior chemotherapy, surgery, or radiotherapy for EAC.
6. Prior mediastinal irradiation (for any reason).
7. Clinically significant ulcerative colitis, inflammatory bowel disease, or partial or
complete small bowel obstruction are to be excluded.
8. Malabsorption syndrome or other condition that would interfere with intestinal
absorption are excluded.
9. Pregnant or nursing females are to be excluded. Pregnant women are excluded from this
study because LY2940680 is a Hh pathway-inhibiting agent 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
LY2940680, breastfeeding should be discontinued if the mother is treated with
LY2940680. These potential risks may also apply to other agents used in this study.
10. Presence of other significant cancer(s) or history of other significant cancer(s)
within the last 3 years (patients who have been cancer-free for 3 years, or have a
history of completely resected non-melanoma skin cancer or successfully treated in
situ carcinoma of the cervix are eligible).
11. Known viral or other chronic types hepatitides or cirrhosis.
12. Uncontrolled concurrent illness including, but not limited to: serious uncontrolled
infection, symptomatic congestive heart failure (CHF), unstable angina pectoris,
cardiac arrhythmia that interfere with blood pressure, uncontrolled diabetes, or
psychiatric illness/social situations that would limit compliance with the study
requirements.
13. Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia
defined as less than the lower limit of normal for the institution, despite adequate
electrolyte supplementation.
14. Patients who are receiving concurrent non-protocol anti-cancer therapy (chemotherapy,
radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy,
biologic therapy, or tumor embolization) are to be excluded.
15. Patients may not be receiving any other investigational agents.
16. Patients with known hypersensitivity to taxanes or platinums are to be excluded.
17. Patients taking medications with narrow therapeutic indices that are metabolized by
cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible.
Patients on strong CYP3A inhibitors will also be excluded.
18. HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with LY2940680. In addition, these
patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy.
19. Any other conditions or circumstances that would, in the opinion of the Investigator,
make the patient unsuitable for participation in the study.
Locations and Contacts
Jaffer Ajani, MD, Phone: 713-792-2828
University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States; Not yet recruiting
Additional Information
University of Texas MD Anderson Cancer Center Website
Starting date: November 2015
Last updated: August 19, 2015
|