RTOG 1010

KCCOP Protocol Summary

The summary below serves as a brief review of the treatment plan and eligibility for the protocol.
This summary is not intended to be used in place of the full eligibility & treatment information in the protocol.
Please follow the "Full Protocol" link or contact KCCOP for complete protocol information.

Full Protocol

(members only)

Consent Form

HIPAA

RTOG 1010 - "A Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of HER2-Overexpressing Esophageal Adenocarcinoma"

NOTE: See 3D-CRT credentialing requirements in protocol Section 5.1. No IMRT is allowed.

Treatment Plan (Supplied Drug: Trastuzumab)

STEP 1 REGISTRATION

HER2 TESTING (MANDATORY tissue submission)

Tumor tissue must be received & confirmed HER2+ b/f randomization. No HER2- pts will be randomized.

STEP 2 REGISTRATION

RANDOMIZATION

Arm 1

Trastuzumab: 4mg/kg, IV, Day 1

Trastuzumab: 2mg/kg, IV, Days 8, 15, 22, 29, 36

Trastuzumab: 6mg/kg, IV, Day 57

Paclitaxel: 50mg/m2, IV, Days 1, 8, 15, 22, 29, 36

Carboplatin: AUC=2, Days 1, 8, 15, 22, 29, 36

RT: 50.4Gy at 180cGy/fx, Days 1-5, 8-12, 15-19, 22-26, 29-33 & 36-38 (IMRT not allowed. Begin w/i 10 days after STEP 2 registration.)

Maintenance Trastuzumab: 6mg/kg, IV, q3wks x 13 tx (start >21 & <56 days post-surg recovery)

Arm 2

Paclitaxel: 50mg/m2, IV, Days 1, 8, 15, 22, 29, 36

Carboplatin: AUC=2, Days 1, 8, 15, 22, 29, 36

RT: 50.4Gy at 180cGy/fx, Days 1-5, 8-12, 15-19, 22-26, 29-33 & 36-38 (IMRT not allowed. Begin w/i 10 days after STEP 2 registration.)

Eligibility

Path-confirmed primary esophageal adenocarcinoma (w/i 56 days pre-Step 2 regist) involving mid (up to 25cm), distal, or GE junction. May involve stomach up to 5cm.
Must have endoscopy w/bx.

PRIOR TO STEP 1 REGISTRATION, BUT <56 DAYS PRIOR TO STEP 2 REGISTRATION

Must submit tissue for central HER2 testing.
Stg T1N1-2, T2-3N0-2 (AJCC 7th edition) based on:
- Chest/abdominal/pelvic CT or whole-body PET/CT (NOTE: If CT is performed now, whole-body PET/CT is required prior to Step 2 regist.). If adenopathy is noted on scan, an EUS is not required prior to Step 2 regist if adequate tissue has been obtained for central HER2 testing.
- May have regional adenopathy including para-esophageal, gastric, gastrohepatic, & celiac nodes. If celiac adenopathy present, must be <2cm.
- If tumors at level of carina or above, must have bronchoscopy to r/o fistula.
Age <18.
Zubrod 0-2.
ANC >1500 cells/mm3; platelets >100,000 cells/mm3; Hgb >8.0g/dl (transfusion/other intervention to achieve Hgb is allowed); creat <2x ULN; bili <1.5x ULN; SGOT <3x ULN; negative serum or urine pregnancy test (if applicable).
No cervical esophageal carcinoma.
No prior systemic chemo for esophageal cancer. Prior chemo for a different cancer is allowed.
No prior RT for esophageal cancer or prior chest RT.
No prior anthracycline or taxane.
No tracheoesophageal fistula or invasion into trachea or major bronchi.
No prior invasive malignancy (except non-melanoma skin cancer), unless disease-free >2 yrs. In situ carcinomas of breast, oral cavity, or cervix are allowed.
No medical contraindications to esophagectomy.
No prior therapy w/agent targeting the HER2 pathway or HER1 (EGFR) pathway.
No prior Trastuzumab.
No allergic reaction to study drugs involved in this protocol or to a monoclonal antibody.
No hx of CHF.
No unstable angina w/i last 6 mos; transmural MI w/i last 6 mos; acute bacterial or fungal infection requiring IV antibiotics at regist; or AIDS based on current CDC definition (HIV testing is not required); or possibly immunocompromised pts.
Signed informed consent.

PRIOR TO STEP 2 REGISTRATION (HER2+ PTS ONLY)

HER2 expressing esophageal adenocarcinoma centrally assessed w/i 56 days pre-Step 2 regist.
Surgical consult to confirm pt is suitable to curative resection after completion of chemoradiation w/i 56 days pre-Step 2 regist.
RT consult to confirm disease can be encompassed in RT field w/i 56 days pre-Step 2 regist.
Med onc consult w/i 56 days pre-Step 2 regist.
Stg T1N1-2, T2-3N0-2 (AJCC 7th edition) based on:
- H&P, wt w/i 14 days pre-Step 2 regist
- Whole-body PET/CT w/i 56 days pre-Step 2 regist (if only CT performed pre-Step 1 regist)
- EUS w/i 56 days pre-Step 2 regist, unless found to have adenopathy per CT or whole-body PET/CT scan
- EKG w/i 56 days pre-Step 2 regist
- Serum creat <2x ULN w/i 14 days pre-Step 2 regist
Zubrod 0-2 w/i 14 days pre-Step 2 regist.
Negative serum pregnancy test w/i 14 days pre-Step 2 regist (if applicable).
LVEF >ILLN by cardiac echo or MUGA w/i 56 days pre-Step 2 regist.
Women/Men of reproductive potential must use effective contraception while on study & >60 days following last dose of chemo or Trastuzumab.

PRESTUDY REQUIREMENTS

Path-confirmed dx*
Endoscopy w/bx*
EUS (if no adenopathy on CT or whole-body PET/CT)#
HER2 status by central lab#%
H&P w/wt$
Chest/abdomen/pelvic CT or whole-body PET/CT*#
Bronchoscopy (if tumor at level of carina or above)#
EKG#
Med/RT/Surg consults#
Echo or MUGA for LVEF#
Perf status*
CBC w/diff, ANC, platelets, Hgb*
Na, K, BUN, creat, glucose*
Bili, SGOT*
Pregnancy test (if applicable)**
ABG (recommended)#
PFTs#
Plasma/Urine for banking (b/f tx start)***&
Whole blood for banking (b/f tx start or at any other visit during or after tx)***&
Tissue for banking (if pt consents; for all pts)@&

* Pre-Step 1 regist, but w/i 56 days prior to Step 2 regist.

** Urine or serum prior to Step 1 regist & serum w/i 14 days pre-Step 2 regist

*** With pt's consent; HER2+ pts only

# Within 56 days pre-Step 2 regist

$ Within 14 days pre-Step 2 regist

@ From diagnostic bx (if performed) & from EUS (if performed)

% Representative H&E stained slides & corresponding PE tissue block of tumor (or 12 unstained 5-micron sections on plus slides from prim block). A 2nd bx for additional path material is highly recommended from EUS, if performed. Send via FedEx to: Murray Resnick, MD, PhD; Rhode Island Hospital; Providence, RI. Send material from initial endoscopy as soon as it is available. Material from EUS (if performed) should be sent separately.

& Contact KCCOP for kits. Tissue: 1 FFPE block residual prim tumor or 2mm punch (removed at esophagectomy surgery). Plasma: 5-10mL anticoagulated whole blood in purple/lavender top EDTA tube #1 (b/f tx start). DNA: 5-10mL anticoagulated whole blood in purple/lavender top EDTA tube #2 (b/f tx start or at any visit during or after tx). Urine: 10-20mL clean catch (b/f tx start). Process per protocol & send to RTOG Biospecimen Resource; San Francisco, CA. Ship tissue ambient. Send plasma, whole blood, & urine via overnight carrier (Mon-Wed only) frozen on dry ice.