Amivantamab + Chemotherapy for Colorectal Cancer (OrigAMI-1 Trial)
Recruiting in Palo Alto (17 mi)
+94 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Janssen Research & Development, LLC
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial is testing a new medicine called amivantamab on patients with advanced colorectal cancer. The medicine helps the immune system find and destroy cancer cells. Researchers want to see how well it works alone and with standard chemotherapy.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.
What data supports the effectiveness of the drug combination Amivantamab + Chemotherapy for Colorectal Cancer?
Research shows that combinations of chemotherapy drugs like fluorouracil (5-FU), leucovorin, oxaliplatin, and irinotecan have improved survival rates in colorectal cancer patients. These combinations are standard treatments and have shown to be effective in both early and advanced stages of the disease.
12345Is the combination of Amivantamab and chemotherapy safe for treating colorectal cancer?
The safety of chemotherapy combinations like 5-fluorouracil (5-FU), leucovorin, irinotecan, and oxaliplatin has been studied in colorectal cancer, showing they are generally safe with manageable side effects. However, specific safety data for Amivantamab combined with these chemotherapies in colorectal cancer is not provided in the available research.
36789What makes the drug Amivantamab + Chemotherapy unique for colorectal cancer?
This treatment combines Amivantamab, a novel drug targeting specific cancer cell pathways, with established chemotherapy agents like Fluorouracil, Irinotecan, Leucovorin, and Oxaliplatin, which are standard in colorectal cancer treatment. The inclusion of Amivantamab, which is not typically used for colorectal cancer, may offer a new approach by potentially enhancing the effectiveness of the chemotherapy regimen.
12101112Eligibility Criteria
This trial is for adults with advanced colorectal cancer that can't be removed by surgery or has spread. They must have a specific performance status, agree to a tumor biopsy, and not be pregnant. People with certain genetic mutations or brain metastasis are excluded.Inclusion Criteria
I am fully active or restricted in physically strenuous activity but can do light work.
I have been diagnosed with a type of colon or rectal cancer that cannot be removed by surgery.
I agree to have a biopsy of my tumor as required by the study.
Exclusion Criteria
My cancer has a specific mutation identified through a blood test.
I have a history of cancer spreading to the lining of my brain and spinal cord.
I have brain metastasis that is causing symptoms or hasn't been treated.
Participant Groups
The study tests amivantamab alone and alongside standard chemotherapy (Fluorouracil, Leucovorin, Oxaliplatin, Irinotecan) in patients with metastatic colorectal cancer. It aims to find the safest dose when combined with chemo and measure its effectiveness against tumors.
3Treatment groups
Experimental Treatment
Active Control
Group I: Cohorts A, B, and C: Amivantamab MonotherapyExperimental Treatment1 Intervention
Participants with left-sided colorectal cancer (CRC) in Cohort A (no prior anti-epidermal growth factor receptor \[EGFR\] therapy) and in Cohort B (post anti-EGFR therapy), and right-sided CRC in Cohort C (with or without anti-EGFR therapy), will be administered intravenous (IV) infusion of amivantamab 1050 milligrams (mg) if body weight (BW) is less than (\<) 80 kilograms (kg) or 1400 mg if BW is greater than or equal to (\>=) 80 kg, as monotherapy on Days 1 and 15 of Cycle 2 (28-days cycle).
Group II: Cohorts Ph1b-E and E: Amivantamab+5-Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI)Active Control4 Interventions
Participants who are anti-EGFR treatment naïve, have not received irinotecan-based chemotherapy in the metastatic setting, will be administered IV infusion of amivantamab along with FOLFIRI SOC chemotherapy on Days -1, -2, and 8 of Cycle 1 and Days 1 and 15 of Cycle 2 in Ph1b-E. For Cohort E, RP2CD determined in Ph1b-E will be administered.
Group III: Cohorts Ph1b-D and D: Amivantamab+5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6)Active Control4 Interventions
Participants who are anti-EGFR treatment naïve, have not received oxaliplatin-based chemotherapy in the metastatic setting, will be administered IV infusion of amivantamab 1050 or 700 mg (dose level 0 \[DL0\]) if BW is \<80 kg, or 1400 or 1050 mg (dose de-escalation \[DL-1\]) if BW is \>= 80 kg, on Days -1, -2, 8 and 22 of Cycle 1 and along with mFOLFOX6 SOC chemotherapy on Days 1 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 (each cycle of 28 days) in Phase 1b dose confirmation Cohort (Cohort Ph1b-D). Participant in Phase 2 Cohort (Cohort D) will receive recommended Phase 2 combination dose (RP2CD) of amivantamab along with mFOLFOX6 SOC chemotherapy determined in Cohort Ph1b-D.
Amivantamab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Rybrevant for:
- Locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations
- Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations
🇪🇺 Approved in European Union as Rybrevant for:
- Locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations
- Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
BC Cancer Agency - Vancouver BCVancouver, Canada
Cross Cancer InstituteEdmonton, Canada
O Neal Comprehensive Cancer Center at UABBirmingham, AL
University of Maryland School of MedicineBaltimore, MD
More Trial Locations
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Who is running the clinical trial?
Janssen Research & Development, LLCLead Sponsor
References
Role of adjuvant therapy in surgically resected colorectal carcinoma. [2019]An important advance in cancer treatment has been made in recent years with the finding that adjuvant therapy can significantly improve the survival of patients with colorectal cancer. In patients with resected lymph node-positive colon carcinomas (TNM stage 3), adjuvant 5-fluorouracil and levamisole produced an unequivocal survival advantage that established this combination as the standard of clinical practice. Given that biochemical modulation of fluorouracil by leucovorin can increase response rates in advanced disease, this combination is undergoing evaluation as an adjuvant treatment. Preliminary results indicate that 5-fluorouracil and leucovorin are effective in reducing disease relapse; however, the effect of this regimen on patient survival rates awaits extended follow-up. In the treatment of stages 2 and 3 rectal cancer, significant reductions in local recurrence and death rates have been achieved with the combination of 5-fluorouracil and radiation therapy. Immunologic approaches and newer chemotherapeutic agents may further improve patient outcome and are under investigation, as are efforts to reduce the toxic effects of cancer chemotherapy. Increased understanding of the biology of these diseases is likely to yield prognostic markers capable of identifying subgroups of earlier stage patients at high risk of disease relapse who may also benefit from adjuvant therapy.
Rapid evolution in colorectal cancer: therapy now and over the next five years. [2007]A large number of patients with colorectal cancer have relatively early disease, and thus, adjuvant therapy has the potential to save lives. In stage III patients, there has been a steady improvement in 3-year disease-free survival with the use of 5-fluorouracil/leucovorin (5-FU/LV) regimens and capecitabine (Xeloda); Hoffmann-La Roche Inc., Nutley, NJ, http://www.rocheusa.com) regimens. A median survival longer than 20 months was observed in patients with metastatic disease when treated with combination chemotherapy containing oxaliplatin (Eloxatin); Sanofi-Synthelabo Inc., New York, http://www.sanofi-synthelabo.us) or irinotecan (Camptosar); Pfizer Pharmaceuticals, New York, http://www.pfizer.com). This has led to 5-FU/LV/oxaliplatin becoming standard therapy, along with 5-FU/LV/irinotecan. New data confirm the beneficial effect on disease-free survival of adding oxaliplatin to adjuvant colorectal cancer regimens based on 5-FU. These regimens show an effect when given in bolus as well as in infusional schedules. Interest in future adjuvant regimens focuses on the potential additional benefit of molecularly targeted agents, such as bevacizumab (Avastin); Genentech, Inc., South San Francisco, CA, http://www.gene.com), and on the ability of applied genomics to distinguish between high- and low-risk populations.
Update on European adjuvant trials with irinotecan for colorectal cancer. [2018]Recent combinations of chemotherapy have significantly improved the response rate and survival time for patients with metastatic colorectal cancer. This improvement has been initially demonstrated with the combination of fluorouracil (5-FU)/leucovorin and irinotecan (CPT-11, Camptosar), which now is considered and recommended as first-line treatment. The combination of improved efficacy with survival benefit should translate into a better cure rate in patients with resected, locally advanced, nonmetastatic colorectal cancer for whom adjuvant chemotherapy with 5-FU/leucovorin is of proven benefit. Several randomized phase III trials are ongoing in Europe or would begin shortly to assess the potential benefit of a 5-FU/leucovorin-irinotecan combination in the adjuvant setting for patients with stage II or III colorectal cancer. This article will review the inclusion criteria and goal of these European trials. An update on accrual and on tolerance will also be provided.
FOLFOXIRI plus biologics in advanced colorectal cancer. [2020]The combination of oxaliplatin, irinotecan, fluorouracil (5-FU), and leucovorin (FOLFOXIRI) results in improved outcomes compared with standard chemotherapy when used in frontline to treat patients with metastatic colorectal cancer (mCRC). FOLFOXIRI has been recently combined with biologic agents aiming further improvement in outcomes.
Seeing the forest through the trees: a systematic review of the safety and efficacy of combination chemotherapies used in the treatment of metastatic colorectal cancer. [2018]Combinations of fluoropyrimidines with oxaliplatin or irinotecan plus a biologic agent are standard treatments for metastatic colorectal cancer (mCRC). Recent approvals of first-line cetuximab, second-line ziv-aflibercept, and regorafenib as salvage therapy have increased the complexity of the treatment armamentarium. To define optimal regimens, we systematically reviewed combination chemotherapy trials (N=83). Descriptive analyses focusing on fluoropyrimidine formulation, oxaliplatin vs irinotecan combinations, and compatibility with biologics indicated the following: infusional 5-fluorouracil (5-FU) yielded better efficacy and safety than bolus 5-FU. Capecitabine had similar outcomes and better safety than 5-FU with oxaliplatin but not irinotecan. First-line oxaliplatin and irinotecan appeared equivalent. Antiangiogenics, such as bevacizumab and ziv-aflibercept, and epidermal growth factor receptor-targeted monoclonal antibodies cetuximab and panitumumab further improved efficacy. The treatment landscape for mCRC has become complex, and we are approaching individualized therapy based on predictive factors, including KRAS mutational status. Appropriate administration of chemotherapy/biologic combinations is critical.
Antitumour activity of three second-line treatment combinations in patients with metastatic colorectal cancer after optimal 5-FU regimen failure: a randomised, multicentre phase II study. [2020]We have investigated the efficacy, safety and quality of life profiles of three therapeutic combinations [irinotecan + leucovorin (LV)/5-fluorouracil (5-FU), oxaliplatin + LV/5-FU and irinotecan +oxaliplatin] in patients with metastatic colorectal cancer after failure of a 5-FU-based regimen, or whose disease had progressed within 6 months of the end of treatment.
The comparison of FOLFOX regimens with different doses of 5-FU for the adjuvant treatment of colorectal cancer: a multicenter study. [2021]We aim to compare the efficiency and toxicity of three different 5-fluorouracil (5-FU) administration types in 5-FU, leucovorin, and oxaliplatin (FOLFOX) combination treatment for adjuvant therapy in colorectal cancer (CRC).
Efficacy and safety of addition of bevacizumab to FOLFIRI or irinotecan/bolus 5-FU/LV (IFL) in patients with metastatic colorectal cancer: A meta-analysis. [2022]Recent studies have paid much attention on the safety of bevacizumab as adjuvant chemotherapy for metastatic colorectal cancer. The aim of this meta-analysis was to study the efficacy and safety of bevacizumab in combination with irinotecan, bolus followed by infusional 5-fluorouracil, and leucovorin (FOLFIRI) and, irinotecan, bolus fluorouracil, leucovorin (IFL) for patients with metastatic colorectal cancer (mCRC).An electronic search of related trials was conducted from PubMed, EMBASE, Cochrane Library databases. Risk ratio (RRs) and its 95% confidence intervals (95% CIs) were calculated by using either DerSimonian-Laird method or Mantel-Haenszel method according to the heterogeneity of included articles. The risk of mortality, therapeutic efficacy, and adverse effect were meta-analyzed.In total, 6 RCTs including 2165 participants (1109 in the treatment group, 1056 in the control group) were included in this meta-analysis. Compared with FOLFIRI-panitumumab/cetuximab, the bevacizumab addition significantly reduced the complete response (CR) rate (RR [95%CI] = 0.31[0.11, 0.89], P = 0.03) and the risk of grade 3/4 adverse event (RR [95%CI] = 0.89[0.80, 0.98], P = 0.01). Compared with FOLFIRI and IFL alone, the addition of bevacizumb significantly increased the partial response (PR) and objective response (OR) rates. Compared with IFL alone, the addition of bevacizumb significantly reduced the mortality risk of PFS (RR [95%CI] = 0.53[0.42, 0.66], P
Cetuximab plus XELIRI or XELOX for first-line therapy of metastatic colorectal cancer. [2018]Modern chemotherapy combinations for metastatic colorectal cancer (mCRC) comprise infusional 5-fluorouracil (5-FU), leucovorin, and irinotecan or oxaliplatin. The fluoropyrimidine derivative capecitabine is at least as effective as 5-FU plus leucovorin bolus regimens. It displays a favorable toxicity profile and offers the advantages of oral administration. The epidermal growth factor receptor antibody cetuximab induces synergistic antitumor activity when combined with chemotherapy. In pretreated patients, cetuximab can restore the sensitivity to irinotecan and, therefore, has been registered in this setting. Several phase I/II trials have investigated the combination of cetuximab with irinotecan-based or oxaliplatin-based chemotherapy for the first-line treatment of mCRC. These combinations have been proven to be safe and have provided promising efficacy data. A recent phase III trial confirmed improved progression-free survival, response rates, and a particularly significant increase of secondary resection rates for the combination of FOLFIRI (infusional 5-FU/leucovorin/irinotecan) plus cetuximab compared with FOLFIRI alone. In this review, we discuss the background of combining XELIRI (capecitabine/irinotecan) or XELOX (capecit-abine/oxaliplatin) with cetuximab for the first-line treatment of mCRC and present available data of these combined cytotoxic and targeted treatment approaches.
[Systemic treatment of colorectal cancers--factual standards and perspectives]. [2018]Adjuvant therapy has been shown to reduce recurrence and improve survival in patients with stage III colo-rectal cancer (CRC). However, the use of adjuvant therapy is still much debated in stage II disease. Fluorouracil (5-FU) and folinic acid (FA) are currently the standard adjuvant drug combination. The treatment of patients with metastatic colorectal cance has changed dramatically over the years. The more optimal use of 5-FU in association with FA, the new drugs such as irinotecan and oxaliplatin, and the oral fluoropyrimidines capecitabine and uracil/tegafur(UFT) have contributed to the increased therapeutic option and to improved outcome of patients with metastatic CRC. It has been shown that combination therapy with 5-FU/FA and irinotecan or oxaliplatin is more active than 5-FU/FA in the first line of advanced CRC. The oral fluoropyrimidines capecitabine and UFT/FA seem to have a comparable activity to intravenous bolus 5-FU/FA in the first line treatment of metastatic CRC. New agents acting on novel targets are under development. Epidermal growth factors inhibitors, vascular endothelial growth inhibitors, and cyclo-oxygenase 2 inhibitors might play a role in the future in the treatment of CRC.
[Controversy of treatment for advanced colorectal cancer--intermedisine]. [2018]Until recently, few chemotherapy options were available to treat metastatic colorectalcancer. For years, the standard chemotherapy has been a Fluorouracil (5-FU) alone of 5-FU with leucovorin (LV) modulation. The newer cytotoxic drugs irinotecan (CPT-11) and oxaliplatin (L-OHP) has generated further improvement in survival. Additionally, improvement in convenience of drug administration has been achieved with the development of oral fluoropynmidines. In randomized trials, oral fluoropyrimidines were equally effective to bolus 5-FU and LV. Recently completed or ongoing clinical trials to study novel targeting agents have initiated a new generation of drug development such as angiogenesis inhibitors and epidermal growth factor inhibitors. Randomized trials will determine the impact of these newer agents on survival and quality of life.
European experience with irinotecan plus fluorouracil/folinic acid or mitomycin. [2018]Tremendous progress has been made in the medical treatment of advanced colorectal cancer during the past 2 to 3 years, due to the availability of several new drugs. Of these new agents, irinotecan (CPT-11 [Camptosar]) seems to be one of the most active against advanced colorectal cancer. It is, therefore, a good candidate for combination with the more classic cytotoxic agents for this disease. This article summarizes several European phase I and II studies in which irinotecan has been combined with (1) fluorouracil (5-FU) alone, given as a repeated bolus injection or a protracted infusion; (2) 5-FU modulated by folinic acid (leucovorin) according to different schedules; or (3) mitomycin (Mutamycin). All of these studies have demonstrated clinical responses in patients with advanced colorectal carcinoma, including complete responses. The toxicity profiles of the various combinations seem to be acceptable; neutropenia and delayed diarrhea are the most frequent side effects. Large phase III studies are still warranted to demonstrate the benefit of these irinotecan-based regimens.