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Cola

Phase 2 (Squamous Cell Carcinoma of the Head and Neck)

PX-866 administered at the MTD/RD in combination in patients administered weekly on a 21 day cycle.

PX-866 (SCCHN)

Cetuximab administered weekly on a 21 day cycle, as standard of care in patients.

Cetuximab (SCCHN)

PX-866 (CRC)

Cetuximab administered weekly on a 21 day cycle in patients, as standard of care.

Cetuximab (CRC)

Diana Hausman, MD

The purpose of this Phase 1/2 open-label study is to determine the safety and efficacy of a cetuximab and PX-866 combination treatment. In the Phase 1 part of the study, the dose of PX-866 to be given in combination with cetuximab will be determined in patients with incurable metastatic CRC or incurable progressive, recurrent or metastatic SCCHN. The Phase 2 part of the study is a randomized evaluation of the antitumor activity and safety of PX-866 in combination with cetuximab versus cetuximab alone in patients with either incurable metastatic CRC who have a history of progression or recurrence following prior irinotecan and oxaliplatin containing regimens or are intolerant of irinotecan (Group 1) or incurable progressive, recurrent or metastatic SCCHN (Group 2).

Phase 1 will determine the maximally tolerated or recommended dose of PX-866 to be given orally on Days 1-21 in combination with cetuximab 250 mg/m2 administered IV weekly on Days 1, 8, and 15 of a 21-day cycle. All patients will receive an initial loading dose of 400 mg/m2 cetuximab rather than 250 mg/m2 on Cycle 1 Day 1. Patients may receive premedication with an H1 antagonist per the cetuximab package insert. Up to 3 dose levels of PX-866 will be evaluated to determine the MTD/RD in cohorts of up to 6 patients using a standard 3+3 dose-escalation design. At least 6 patients will be treated at the MTD/RD. All patients in Phase 1 will be required to undergo PK assessments during Cycle 1 Week 3 to measure cetuximab levels. Exploratory PD assessments will include evaluation of changes in levels of fasting C-peptide as well as changes in EGFR and PI-3K signaling pathways in peripheral blood mononuclear cells (PBMC) and platelets. Additional optional evaluations will include changes in EGFR and PI-3K signaling in paired tumor biopsies provided before and after one cycle of treatment. All patients will be asked, but not required, to provide an archived tumor biopsy sample for evaluation for potential biomarkers of response to PX-866 and cetuximab.

Phase 2 is an open-label, randomized evaluation of the antitumor activity and safety of PX-866 administered orally or via PEG tube (if applicable) at the MTD/RD in combination with cetuximab, versus cetuximab alone in cetuximab-naïve patients with incurable metastatic CRC who have a history of progression or recurrence following prior irinotecan and oxaliplatin containing regimens or are intolerant of irinotecan (Group 1) or patients with incurable progressive, recurrent or metastatic SCCHN (Group 2). Seventy two evaluable patients (36 patients per arm) will be evaluated per indication. Patients will be randomized 1:1 to receive PX-866 + cetuximab or cetuximab alone.

Phase 1 and 2 Study of PX-866 and Cetuximab

Phase 1/2 Study of PX-866 and Cetuximab

Cascadian Therapeutics Inc.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase 1 and 2 Study of PX-866 and Cetuximab	NCT01252628	Incurable Metas... Incurable Progr...	PX-866 (SCCHN) Cetuximab (SCCH... PX-866 (CRC) Cetuximab (CRC)	18 Years -	Seagen Inc.
Phase 1 and 2 Study of PX-866 and Cetuximab	NCT01252628	Incurable Metas... Incurable Progr...	PX-866 (SCCHN) Cetuximab (SCCH... PX-866 (CRC) Cetuximab (CRC)	18 Years -	Seagen Inc.

Spots Global Cancer Trial Database for incurable progressive, recurrent or metastatic squamous cell carcinoma of the head and neck