Cetuximab and Savolitinib Treatment of Ras Wild-Type Colorectal Cancer

NCT02630420 | Withdrawn Phase 1 DMC

• 1 other identifier: 1502015402
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Two-part phase 1B clinical trial combining cextuximab and savolitinib for treating Ras wild-type colorectal cancer (CRC). Part 1 will assess the safety and tolerability of this drug combination and will include patients with squamous cell carcinoma of the head and neck cancer, as well as patients with CRC. Part 2 of the study, the focus of this registration, will obtain further safety data for the combination of cextuximab and savolitinib and will look at the efficacy of cextuximab and savolitinib in Ras wild-type mCRC that was previously treated and relapsed on cetuximab or panitumumab.Correlative studies will examine tumor and blood specimens for mechanisms of anti-EGFR resistance and response to MET inhibition.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability based on regular clinical assessment and NCI Common Terminology Criteria for Adverse Events

  start of treatment to 3 years from treatment initiation

Secondary Outcomes (2)

• Response to treatment measured by RECIST (Response Evaluation Criteria in Solid tumors) criteria

  start of treatment to disease progression/recurrence, up to 3 years

• Progression free survival

  start of treatment to disease progression, up to 3 years

Other Outcomes (4)

• HGF/MET pathway activation as a predictor of response to therapy.

  3 years from start of treatment

• Genetic aberrations, assessed by next generation sequencing, as predictors of sensitivity/resistance to treatment.

  3 years from start of treatment

• Changes in HGF/MET pathway activation over the course of the disease measured by comparing archival, baseline and progression samples.

  3 years from start of trial

Study Arms (1)

cetuximab and savolitinib

EXPERIMENTAL

Following assessment in Part 1 of dose-limiting toxicity and maximum tolerated dose, this drug combination will be administered in Part 2 of the study to assess safety, tolerability, response rate, and progression-free survival.

Drug: cetuximab and savolitinib

Interventions

cetuximab and savolitinib DRUG

Dosage of combined cetuximab and savolitinib will be determine in Part 1 of the study, Part 2 will use the findings of Part 1 to further assess safety and to assess efficacy of this drug combination.

cetuximab and savolitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Progressive metastatic or unresectable CRC or SCCHN.
• Prior therapy with cetuximab or panitumumab. Cetuximab and panitumumab could have been used either alone or in combination with other agents.
• If patients were treated with cetuximab in the past, they must have been able to tolerate full doses of cetuximab without dose modifications for toxicity.
• ECOG performance status 0-2.
• Life expectancy of at least 3 months.
• Patient with adequate organ function:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Hemoglobin ≥ 9 g/dL
• Platelets (PLT) ≥ 100 x 109/L
• AST/ALT ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastases)
• GGT \< 3 x ULN (\< 5 x ULN in case of liver involvement)
• Bilirubin ≤ 1.5 x ULN
• Albumin ≥ 3 g/dL
• Serum creatinine ≤ 1.5 x institutional ULN (Cockcroft and Gault formula)
• Adequate contraception if applicable.

You may not qualify if:

• Previous treatment with MET inhibitor or anti-MET antibody (e.g. foretinib, crizotinib, cabozantinib, onartuzumab).
• Patients with previous hypersensitivity to cetuximab (Grade 2 or higher, unless controlled to \< Grade 2 with prophylactic measures on subsequent exposures).
• Active dermatological condition requiring treatment with associated grade 2 or higher skin toxicity. Dermatological condition controlled with treatment with maximum of grade 1 skin toxicity will be allowed for study enrollment.
• Symptomatic brain metastases requiring treatment.
• Other active malignancy within the last 3 years (except for non-melanoma skin cancer or a non-invasive/in situ cancer).
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• Persistent toxicities CTCAE grade 2 or higher, with the exception of alopecia, caused by previous cancer therapy.
• Pregnancy or breast feeding.
• Current therapy with other investigational agents or participation in another clinical study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to savolitinib.
• Major surgery within 28 days or minor surgery within 14 days of the start of the study treatment, except for tumor biopsy.
• Radiotherapy less than two weeks prior to the start of the study treatment
• Significant current or recent (\< 14 days) gastrointestinal disorders with diarrhea as a major symptom, e.g. Crohn's disease, malabsorption, or CTCAE grade \> 2 diarrhea of any etiology.
• Psychological, familial, or sociological condition potentially hampering compliance with the study protocol and follow-up schedule.
• Involvement in the planning and/or conduct of the study.

Sponsors & Collaborators

• Yale University: lead

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; 1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Stacey M Stein, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2015
• First Posted: December 15, 2015
• Study Start: January 1, 2017
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: October 26, 2017

Record last verified: 2017-10