AZD0022 + Cetuximab for Solid Tumors
(ALAFOSS-01 Trial)
Recruiting in Palo Alto (17 mi)
+33 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: AstraZeneca
Must not be taking: Herbal medications, CYP3A4/5 drugs
Disqualifiers: Uncontrolled conditions, ILD, brain metastases, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This is a first-in-human, modular, Phase I/IIa, open-label, multi-centre study to assess the safety, tolerability, PK, and preliminary efficacy of AZD0022 monotherapy in combination with other anti-cancer agents in participants with tumours harbouring a KRASG12D mutation.
Will I have to stop taking my current medications?
The trial requires that you stop taking any herbal medications and certain other medications that affect liver enzymes (CYP3A4/5). You may also need to stop other cancer treatments a few weeks before starting the trial.
What data supports the effectiveness of the drug AZD0022 + Cetuximab for solid tumors?
Cetuximab, one of the components of the treatment, has shown some effectiveness in treating non-small-cell lung cancer and colorectal cancer by targeting the epidermal growth factor receptor (EGFR). In particular, it has been approved for use in colorectal cancer and has shown a small benefit in overall survival for certain lung cancer patients, especially those with high EGFR expression.
12345What safety data exists for the treatment AZD0022 + Cetuximab for Solid Tumors?
Cetuximab, used in various cancers, commonly causes skin issues, diarrhea, and tiredness. Rarely, it can lead to serious lung problems, as seen in a fatal case of lung disease. Generally, it is well-tolerated when combined with chemotherapy.
24678How is the drug AZD0022 + Cetuximab different from other treatments for solid tumors?
The combination of AZD0022 and Cetuximab is unique because it targets the epidermal growth factor receptor (EGFR) in solid tumors, potentially offering a new approach for patients who may not respond well to existing treatments. Cetuximab is already used in various cancers, but combining it with AZD0022 could enhance its effectiveness, especially in tumors with high EGFR expression.
23459Eligibility Criteria
This trial is for adults with certain cancers (like lung, pancreatic, or colorectal cancer) that have a specific genetic change called KRASG12D mutation. Participants should be able to receive the treatments and follow the study procedures.Inclusion Criteria
I am at least 18 years old or the legal age of consent.
My cancer is confirmed to be advanced or has spread.
I can provide a formalin-fixed, paraffin-embedded tumor sample.
+11 more
Exclusion Criteria
I am not taking any herbal medications.
I had radiation for cure ≤ 4 weeks ago or palliative radiation ≤ 2 weeks ago.
I have been treated with a KRAS inhibitor before.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Participants receive AZD0022 monotherapy or in combination with Cetuximab to determine the maximum tolerated dose
Part of a 2-year study
Dose Optimisation
Participants receive AZD0022 monotherapy or in combination with Cetuximab to optimize dosing
Part of a 2-year study
Potential Efficacy Expansion
Participants receive AZD0022 monotherapy or in combination with Cetuximab to assess preliminary efficacy
Part of a 2-year study
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study is testing AZD0022 alone and combined with other cancer drugs like Cetuximab. It's an early-stage trial to see how safe it is, how the body processes it, and if it works against these cancers.
7Treatment groups
Experimental Treatment
Group I: Module 2 Part C. Potential Efficacy ExpansionExperimental Treatment2 Interventions
AZD0022 in combination with Cetuximab
Group II: Module 2 Part B. Dose OptimisationExperimental Treatment2 Interventions
AZD0022 in combination with Cetuximab
Group III: Module 2 Part A. Dose EscalationExperimental Treatment2 Interventions
AZD0022 in combination with Cetuximab
Group IV: Module 1 Part C. Potential Efficacy ExpansionExperimental Treatment1 Intervention
AZD0022 monotherapy
Group V: Module 1 Part B. Food Effect CohortExperimental Treatment1 Intervention
AZD0022 monotherapy
Group VI: Module 1 Part B. Dose OptimisationExperimental Treatment1 Intervention
AZD0022 monotherapy
Group VII: Module 1 Part A. Dose EscalationExperimental Treatment1 Intervention
AZD0022 monotherapy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Research SiteFairfax, VA
Research SiteKansas City, MO
Research SiteEdmonton, Canada
Research SiteToronto, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
AstraZenecaLead Sponsor
References
Cetuximab: an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer. [2022]Cetuximab is a recombinant human/mouse chimeric epidermal growth factor receptor (EGFR) monoclonal antibody. It was approved by the US Food and Drug Administration in February 2004 to be used in combination with irinotecan for the treatment of EGFR-expressing, metastatic colorectal cancer in patients who had failed to improve with irinotecan-based chemotherapy. Cetuximab was also approved for administration as a single agent in the treatment of patients with EGFR-expressing, metastatic colorectal cancer who are intolerant to irinotecan-based chemotherapy.
Cetuximab in the treatment of patients with colorectal cancer. [2018]Cetuximab is a chimeric mAb with avidity for the EGFR higher than that of the natural ligands of the receptor. Preclinical studies showed that cetuximab demonstrated synergy with topoisomerase I inhibitors in the treatment of human colorectal cancer (CRC) cell lines in vivo. Subsequent clinical trials have shown that cetuximab can reverse resistance to topoisomerase I inhibitors in addition to having modest monotherapy activity. These studies led to accelerated provisional FDA approval of the drug for the treatment of patients with irinotecan-refractory metastatic CRC. Its clinical utility has been improved with the discovery of negative predictive biomarkers; these have shown that there is a lack of cetuximab benefit for patients whose tumors generally harbor a KRAS mutation, thus sparing these patients the toxicity of the agent which would not be of treatment benefit.
Two cases of acneiform eruption induced by inhibitor of epidermal growth factor receptor. [2018]Cetuximab is a member of a new family of antineoplastic agents that inhibit the epidermal growth factor receptor (EGF-R), and which are increasingly being used in the treatment of solid tumors.
Cetuximab in non-small-cell lung cancer. [2018]Cetuximab is a chimeric human-mouse anti-EGF receptor monoclonal antibody. In Phase I studies, no dose-limiting toxicities were observed with cetuximab as a single agent or combined with chemotherapy; pharmacokinetic and pharmacodynamic analyses supported 250 mg/m(2) weekly administration. Skin toxicity, diarrhea and fatigue were the most common toxicities. The positive results obtained in Phase II trials in patients with advanced non-small-cell lung cancer prompted two randomized Phase III trials evaluating cetuximab in addition to first-line chemotherapy. Both trials showed a small benefit in overall survival for the experimental treatment, which was considered insufficient by the EMA for marketing approval. However, a subgroup analysis of the FLEX Phase III trial recently demonstrated a larger survival benefit from the experimental treatment in patients with high immunohistochemical EGF receptor expression. This finding, if confirmed prospectively, could represent a new opportunity for positioning cetuximab into the standard treatment of advanced non-small-cell lung carcinoma.
Docetaxel or pemetrexed with or without cetuximab in recurrent or progressive non-small-cell lung cancer after platinum-based therapy: a phase 3, open-label, randomised trial. [2020]Available preclinical and phase 2 clinical data suggest that the addition of cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor (EGFR), to chemotherapy might improve outcome in patients with advanced non-small-cell lung cancer (NSCLC). We aimed to assess whether the addition of cetuximab to chemotherapy improved progression-free survival in patients with recurrent or progressive NSCLC after platinum-based therapy.
Synergy between cetuximab and chemotherapy in tumors of the gastrointestinal tract. [2022]Cetuximab is a recently approved monoclonal antibody that targets the epidermal growth factor receptor, a receptor tyrosine kinase involved in the development and progression of colorectal cancer (CRC) and other solid tumors. Cetuximab, as a single agent or in combination with chemotherapy, has demonstrated significant clinical efficacy against CRC. Combinations of cetuximab with chemotherapy have proven to be well tolerated, with minimal overlap of toxicities between agents; and the anticancer synergy between cetuximab and traditional chemotherapy agents has made cetuximab a vital treatment for patients who are no longer responsive to chemotherapy alone. The U.S. Food and Drug Administration approved cetuximab in combination with irinotecan for the treatment of irinotecan-refractory metastatic CRC or as monotherapy for treating patients intolerant to irinotecan. Combination chemotherapies involving cetuximab as well as combinations involving cetuximab and other targeted agents, such as bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, constitute powerful new treatment options for the management of CRC. This review discusses recent clinical studies that have further defined this synergy, focusing primarily on tumors of the gastrointestinal tract.
Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. [2022]This multicenter study evaluated the antitumor activity of cetuximab, an immunoglobulin G1 antibody directed at the epidermal growth factor receptor (EGFR), in metastatic colorectal carcinoma (CRC) refractory to irinotecan, oxaliplatin, and a fluoropyrimidine. It also evaluated the safety, pharmacokinetics, immunokinetics, and biologic determinants of activity.
A case of fatal cetuximab-induced interstitial lung disease during the first weeks of treatment. [2021]Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor. It has demonstrated activity against a number of cancers including lung, head and neck, and colorectal. The most common side effects associated with this agent are dermatological; however, other types of toxicities have been reported with varying frequencies. Here, we report a case of interstitial lung disease that developed within the first 4 weeks of cetuximab treatment initiation in a patient with metastatic colorectal cancer and led to patient death. Early fatal pulmonary events secondary to cetuximab is rarely reported in the literature; this case report highlights the importance of awareness among treating health care professionals of this potentially fatal toxicity.
Cbl-b regulates the sensitivity of cetuximab through ubiquitin-proteasome system in human gastric cancer cells. [2018]Cetuximab is a monoclonal antibody against epidermal growth factor receptor (EGFR) and is approved for clinical use in combination with chemotherapy in patients affected by colorectal cancer (CRC), non small cell lung cancer (NSCLC), and head and neck cancer. Compared with these cancers, gastric cancer is relatively resistant to cetuximab and its regulatory mechanism is still unclear.