NCI Community Oncology Research Program - Protocol Summary
SWOG S1801 - "Phase II Randomized Study of Adjuvant vs. Neoadjuvant MK-3475 (Pembrolizumab) for Clinically Detectable Stage III-IV High-Risk Melanoma."
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 contact NCORP-KC for complete protocol information.
Skin Clinical Trial
CANCER TYPE: Melanoma
RESEARCH BASE: SWOG
NCT NUMBER: NCT03698019
HIPPA FORM: DOWNLOAD HIPPA FORM
Consent Form: VIEW CONSENT FORM
UPDATED ON 01/09/2019 (16:15:07)
Resectable melanoma, stage III or IV, adjuvant vs. neoadjuvant Pembrolizumab.
Treatment Plan (Supplied drug: MK-3475 Pembrolizumab)
Step 1: RANDOMIZATION
Step 2: SURGERY
Patients on Adjuvant arm must be registered to Step 2 (Surgery) within 17 days (preferably within 14 days) after randomization and must undergo surgical resection within 17 days (preferably within 14 days) after Step 2 registration. Radiation is allowed after surgery. However, interval between Surgery and the start of Adjuvant therapy must not exceed 84 days.
Step 3: ADJUVANT THERAPY
Pembrolizumab 200mg, IV, Day 1, Q 3 weeks, for 18 doses
Step 1: RANDOMIZATION AND NEOADJUVANT THERAPY
Pembrolizumab 200mg, IV, Day 1, Q 3 weeks, for 3 doses followed by resection
Step 2: SURGERY
Step 3: ADJUVANT THERAPY
Pembrolizumab 200mg, IV, Day 1, Q 3 weeks, for 18 doses total (pre-op + post-op)
Step 1 Eligibility
- Patients must have resectable melanoma in order to be eligible for this study. Patients must have clinically detectable Stage III (clinically detectable N1b, N1c, N2b, N2c, N3b and N3c) or Stage IV resectable melanoma. Patients with melanoma of mucosal or acral origin are eligible. Patients with melanoma of uveal origin are not eligible. Patients with a history of brain metastases are not eligible.
- Patients are eligible for this trial either at initial presentation of their melanoma or at the time of the first detected nodal, satellite/in-transit, distant metastases, or recurrent disease in prior lymphadenectomy basin or distant site. Nodal, satellite/in-transit metastasis, distant metastases or disease in a prior complete lymphadenectomy basin must have been confirmed histologically by H & E stained slides.
- Patients with multiple regional nodal basin involvement are eligible. Gross or microscopic extracapsular nodal extension is permitted.
- Patients must not have received previous neoadjuvant treatment for their melanoma. Patients may have received prior non-immunotherapy adjuvant therapy. Patients must not have had prior immunotherapy including, but not limited to ipilimumab, interferon alfa-2b, high dose IL-2, PEG-IFN, anti-PD-1, anti-PD-L1 intra-tumoral, or vaccine therapies. Patients must not be planning to receive any of the prohibited therapies listed in Section 7.2 during treatment phases on the study.
- Patients must not be planning to receive concomitant other biologic therapy, hormonal therapy, other chemotherapy, surgery, while on protocol therapy.
- Patients may have received prior radiation therapy, including after prior surgical resection. All adverse events associated with prior surgery and radiation therapy must have resolved to ≤ Grade 1 prior to randomization.
- Patients must be ≥ 18 years of age.
- All patients must have disease status documented by a complete physical examination and imaging studies within 42 days prior to randomization. Imaging studies must include a total body PET-CT scan that is of diagnostic quality with iodine contrast-enhanced images (with or without brain) or a CT of the chest, abdomen and pelvis with intravenous contrast. For patients with melanoma arising from the head and neck, dedicated neck imaging (CT with intravenous contrast or iodine contrast-enhanced PET-CT through the region) is required. If the patient has unknown primary with disease in the axilla, neck imaging is required to assure region is clear of cancer. CT imaging should be done with intravenous contrast if there are no contraindications for it. Any other clinically-indicated imaging studies if performed (e.g. bone scan) must show no evidence of disease.
- All patients must have a CT or MRI of the brain within 42 days prior to randomization. The brain CT or MRI should be performed with intravenous contrast (unless contraindicated).
- Patients must have adequate bone marrow function as evidenced by all of the following: ANC ≥ 1,500/microliter (mcL); platelets ≥ 100,000/mcL; Hemoglobin ≥ 10 g/dL. These results must be obtained within 42 days prior to randomization.
- Patients must have adequate hepatic function as evidenced by the following: total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN) (except patients with Gilbert’s Syndrome, who must have a total bilirubin < 3.0 mg/dL), and SGOT (AST) and SGPT (ALT) and alkaline phosphatase ≤ 2 x IULN. These results must be obtained within 42 days prior to randomization.
- Patients must have LDH performed within 42 days prior to randomization.
- Patients must have adequate creatinine clearance as evidenced by CrCl > 30 mL/min within 42 days prior to randomization.
- Patients must have Zubrod Performance Status ≤ 2 (see Section 10.14).
- Patients must not have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- Patients must not have an active infection requiring systemic therapy.
- Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Patients must not have received live vaccines within 42 days prior to randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
- Patients known to be HIV positive are eligible if they meet the following criteria within 30 days prior to randomization: stable and adequate CD4 counts (≥ 350 mm3), and serum HIV viral load of < 25,000 IU/ml. Patients may be on or off anti-viral therapy so long as they meet the CD4 count criteria.
- Patients must not have known active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection prior to randomization. Note: No testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
- Prior malignancy is allowed providing it does not require concurrent therapy.
- Women of childbearing potential must have a negative urine or serum pregnancy test within 28 days prior to randomization.
- Patients must be deemed medically fit to undergo surgery by the treating medical/surgical team.
- Patients must be willing to submit the following surgical specimens: either all tissue blocks from the surgical specimen or two slides per block [(1) H&E slide and (1) unstained slide OR (2) unstained slides if H&E stained slides cannot be provided)
- Patients must be offered the opportunity to participate in specimen banking as outlined in Section 15.3.
Step 2 Eligibility
- Patients randomized to Arm 2 (Neoadjuvant arm) must be willing to submit tissue to determine pathologic response as described in Section 15.2 regardless of number of pre-operative doses of MK-3475 (pembrolizumab) received. Determination of pathologic response cannot be done on less than the full surgical specimen.
- Patients must have disease assessments by PET-CT with iodinated CT contrast (i.e. diagnostic quality CT) or CT chest/abdomen/pelvis with IV contrast, and neck CT with IV contrast if primary head and neck melanoma, performed within 42 days (+/- 1 week) before surgery. MRI combined with non-contrast CT is an acceptable alternative for patients with CT contrast allergy, but imaging must encompass total body.
Step 3 Eligibility
- Patients must have undergone surgery prior to Step 3 registration. The Step 2 surgery must have completely resected their melanoma.
- Patients with gross positive residual disease at the time of surgery do not qualify as having disease-free status, and, therefore, such patients are not be eligible to register for adjuvant therapy.
- Patients with microscopic residual disease (i.e., positive margins) can be treated with re-excision or radiation, per site discretion, to render the patient disease-free prior to registration of adjuvant therapy.
- Disease-free status must be documented by a complete physical examination and radiographic imaging studies within 60 days prior to Step 3 registration. Imaging studies must include a total body PET-CT that is of diagnostic quality (i.e., iodinated contrast), or a CT of the chest, abdomen, and pelvis.
- For patients with melanoma arising from the head and neck, dedicated neck imaging (CT with IV contrast with PET-CT through the region) is required.
- If the patient has had unknown primary with disease in the axilla, neck imaging is required to assure the region is clear of cancer.
- CT imaging should be done with intravenous contrast if there are no contraindications for it.
- Any other clinically-indicated imaging studies if performed (e.g., bone scan) must show no evidence of disease.
- Patients must be registered to Step 3 no more than 84 days after date of Surgery.