Paclitaxel + Ramucirumab +/- Zanidatamab for Gastroesophageal Cancer

Recruiting at 22 trial locations

Overseen By Chris O'Callaghan

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must be taking: Trastuzumab, Platinum-based chemotherapy

Disqualifiers: Other malignancies, Uncontrolled illness, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

168 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding zanidatamab to the usual treatment can more effectively prevent gastroesophageal cancer from growing or spreading. The standard treatment includes paclitaxel (a chemotherapy drug) and ramucirumab (a targeted therapy). Participants will receive either the standard treatment or the standard treatment plus zanidatamab. Suitable candidates have HER2-positive gastroesophageal cancer that cannot be surgically removed or has spread, and have not responded to previous treatments. Participants must be able to tolerate the treatment and agree to provide necessary health information and samples. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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 your specific situation with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that zanidatamab, used alone or with other treatments, is generally safe for people with certain types of cancer. For those with HER2-positive cancers, such as gastroesophageal cancer, zanidatamab has a manageable safety profile, with most side effects being controllable. Patients who received zanidatamab with other drugs tolerated the treatment well.

Zanidatamab has also been studied in other cancers, including breast, gastric, and lung cancers, and has shown promising results. The side effects were usually manageable and did not prevent its use.

In summary, zanidatamab, when combined with common cancer drugs like paclitaxel and ramucirumab, appears safe. The treatment is generally well tolerated, with most side effects being manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for gastroesophageal cancer because Zanidatamab, when combined with Paclitaxel and Ramucirumab, offers a new approach by targeting HER2, a protein that can promote cancer growth. This is different from the standard treatments, which mainly focus on chemotherapy and anti-angiogenic therapies. The addition of Zanidatamab could potentially enhance treatment effectiveness by specifically attacking cancer cells with high levels of HER2. This targeted action may improve outcomes and provide options for patients who do not respond well to existing therapies.

What evidence suggests that this trial's treatments could be effective for gastroesophageal cancer?

This trial will compare the effectiveness of two treatment regimens for gastroesophageal cancer. One arm will evaluate the combination of Zanidatamab with Paclitaxel and Ramucirumab. Studies have shown that adding Zanidatamab to treatments for HER2-positive cancers, such as gastroesophageal cancer, can help shrink tumors. Zanidatamab has been well tolerated and has demonstrated promising, long-lasting effects against tumors when combined with chemotherapy. In patients who have already received multiple treatments, Zanidatamab, whether used alone or with chemotherapy, has shown a manageable safety profile and encouraging results in reducing tumor size. These findings suggest that Zanidatamab could effectively stop the growth or spread of gastroesophageal cancer. The other arm of this trial will assess the combination of Paclitaxel and Ramucirumab without Zanidatamab. ^{1 2 3 4 6}

Who Is on the Research Team?

Elena Elimova

Principal Investigator

University Health Network, Princess Margaret Cancer Centre, Toronto ON Canada

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced gastroesophageal adenocarcinoma that's HER2 positive. They should have tried a trastuzumab-based therapy without success and be able to handle chemotherapy with paclitaxel and ramucirumab. Participants need to be in good enough health (ECOG status of 0 or 1) and expected to live at least 12 weeks.

Inclusion Criteria

Participants must have a life expectancy of at least 12 weeks at the time of study entry

Participant must be accessible for treatment and follow-up

Participants must consent to the provision of samples of blood, serum and plasma for correlative marker assays

Exclusion Criteria

Participants receiving therapy in a concurrent clinical study

Any condition that does not permit compliance with the protocol

I do not have any active or uncontrolled illnesses.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Paclitaxel and Ramucirumab with or without Zanidatamab

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Paclitaxel
• Ramucirumab
• Zanidatamab

Trial Overview The study tests if adding zanidatamab to the usual treatment (paclitaxel and ramucirumab) can better prevent cancer growth or spread in patients with HER2 positive gastroesophageal adenocarcinoma, compared to the standard care alone.

How Is the Trial Designed?

Group I: Zanidatamab + Paclitaxel and Ramucirumab Experimental Treatment 3 Interventions

Group II: Paclitaxel and Ramucriumab Active Control 2 Interventions

Paclitaxel is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in European Union as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in Canada as Paclitaxel for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Jazz Pharmaceuticals

Industry Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

In a phase II trial involving 111 patients with metastatic gastroesophageal adenocarcinoma, the combination of FOLFIRI and ramucirumab did not meet the primary endpoint of a 6-month overall survival rate of ≥65%, achieving only 54%.

While overall survival rates were similar between FOLFIRI plus ramucirumab and paclitaxel plus ramucirumab, FOLFIRI showed better objective response rates and progression-free survival, particularly in patients previously treated with docetaxel, suggesting potential for further investigation in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for patients with advanced or metastatic gastroesophageal adenocarcinoma with or without prior docetaxel - results from the phase II RAMIRIS Study of the German Gastric Cancer Study Group at AIO. Lorenzen, S., Thuss-Patience, P., Pauligk, C., et al.[2023]

In a study involving 167 patients with advanced gastric cancer, ramucirumab was found to be well tolerated, with a low incidence of severe toxicity (9.6%) and only 3% of patients discontinuing treatment due to adverse effects.

The treatment showed a 20.2% overall response rate and a median overall survival of 8.0 months, indicating that ramucirumab is effective in a real-life setting, consistent with results from previous randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab as Second-Line Therapy in Metastatic Gastric Cancer: Real-World Data from the RAMoss Study. Di Bartolomeo, M., Niger, M., Tirino, G., et al.[2023]

The RAINBOW trial demonstrated that ramucirumab combined with paclitaxel significantly prolongs overall survival and progression-free survival in patients with advanced gastric or gastroesophageal junction cancer.

While no predictive biomarkers for treatment efficacy were identified, several prognostic markers (like CRP and IL-8) were associated with longer survival when baseline levels were low, suggesting they could help in assessing patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarker analyses of second-line ramucirumab in patients with advanced gastric cancer from RAINBOW, a global, randomized, double-blind, phase 3 study. Van Cutsem, E., Muro, K., Cunningham, D., et al.[2023]

In a report of four patients with metastatic gastric or gastroesophageal junction adenocarcinoma treated with ramucirumab and paclitaxel, significant adverse events like grade ⩾2 neutropenia and neuropathy were observed, but these were effectively managed by adjusting the paclitaxel dosage.

Despite the adverse events, all patients achieved a best overall response of complete or partial response lasting between 2.2 to 12.4 months, suggesting that careful management of side effects can allow for continued treatment and potential survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing treatment duration with ramucirumab and paclitaxel by managing chemotherapy-associated toxicity: Review of four cases. Merl, MY., Moye, R., Chatterjee, A., et al.[2020]

Ramucirumab significantly improved overall survival in patients with advanced gastric or gastroesophageal junction adenocarcinoma, both as a monotherapy (355 patients) and in combination with paclitaxel (665 patients), with hazard ratios of 0.78 and 0.81, respectively.

The most common side effects reported were hypertension and diarrhea for the monotherapy, and fatigue, neutropenia, diarrhea, and epistaxis for the combination therapy, indicating a manageable safety profile but with notable adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Ramucirumab for Gastric Cancer. Casak, SJ., Fashoyin-Aje, I., Lemery, SJ., et al.[2023]

The combination of ramucirumab and paclitaxel as second-line therapy in Japanese patients with metastatic gastric adenocarcinoma was found to be safe and well-tolerated, with no dose-limiting toxicities reported in a phase Ib study involving 6 patients.

Patients experienced stable disease or partial response, with a median treatment duration of approximately 12.5 weeks, indicating potential efficacy of this treatment regimen in managing advanced gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase ib study of safety and pharmacokinetics of ramucirumab in combination with paclitaxel in patients with advanced gastric adenocarcinomas. Ueda, S., Satoh, T., Gotoh, M., et al.[2023]

In a randomized phase II trial involving 87 patients with metastatic esophageal or gastroesophageal junction cancers, the combination of paclitaxel and cixutumumab did not show a significant improvement in progression-free survival compared to paclitaxel alone, with median PFS of 2.6 months versus 2.3 months, respectively.

Both treatment arms were well tolerated, but the addition of cixutumumab did not enhance overall survival, which was 6.7 months for paclitaxel alone and 7.2 months for the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel With or Without Cixutumumab as Second-Line Treatment of Metastatic Esophageal or Gastroesophageal Junction Cancer: A Randomized Phase II ECOG-ACRIN Trial. Stockton, S., Catalano, P., Cohen, SJ., et al.[2023]

Ramucirumab significantly improves overall survival and progression-free survival in adults with advanced gastric or gastro-oesophageal junction adenocarcinoma, based on results from two phase III trials (REGARD and RAINBOW) involving patients treated with 8 mg/kg every 2 weeks.

The treatment is generally well-tolerated, with hypertension being the most common serious side effect, making ramucirumab a valuable second-line therapy option for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab: A Review in Advanced Gastric Cancer. Greig, SL., Keating, GM.[2023]

In a study of 1063 patients with advanced gastric or gastroesophageal junction cancer, the combination of ramucirumab and paclitaxel showed an objective response rate of 15.1% and a disease control rate of 57.7%, indicating its efficacy as a second-line treatment.

The median overall survival for patients receiving this treatment was 10.03 months, with notable safety concerns including a 35.1% incidence of neutropenia and 10.5% incidence of anemia, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab plus paclitaxel as second-line treatment in patients with advanced gastric or gastroesophageal junction adenocarcinoma: a nationwide real-world outcomes in Korea study (KCSG-ST19-16). Han, HS., Kim, BJ., Jee, HJ., et al.[2022]

In a study of 1590 patients with metastatic gastric and lower esophageal adenocarcinoma, the combination of ramucirumab and paclitaxel used after the first line of chemotherapy was associated with improved overall survival (OS), indicating its efficacy in this patient population.

Factors such as younger age and lower comorbidity were linked to higher rates of palliative chemotherapy use, highlighting the need for further research to address disparities in treatment access, especially for patients in rural areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Ramucirumab Plus Paclitaxel Among Patients With Previously Treated Metastatic Gastric/Lower Esophageal Cancer: A Real-world Study. Abdel-Rahman, O., Mulder, K., Easaw, J.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06043427

Paclitaxel and Ramucirumab +/- Zanidatamab in HER2 ... The addition of zanidatamab to the usual approach could shrink cancer. But, it could also cause side effects. This study will help the study doctors find out if ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.3_suppl.164

Zanidatamab (ZW25) in HER2-expressing ... Zanidatamab, both as a single agent and in combination with chemotherapy, is well tolerated with promising and durable anti-tumor activity in heavily ...

3. nature.com nature.com/articles/s41467-025-59279-z

Zanidatamab monotherapy or combined with ... In heavily pre-treated patients with HER2-expressing GEA, zanidatamab ± chemotherapy had a manageable safety profile and promising antitumor activity.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11871714/

Exploring Zanidatamab's efficacy across HER2-positive ... Zanidatamab has shown promising clinical outcomes in several HER2-positive cancers, including biliary tract, breast, gastric, and lung cancers.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11611523/

State of the art and upcoming trends in HER2-directed ... This review critically evaluates the evolution and current status of HER2-directed therapies in upper gastrointestinal (GI) malignancies.

6. withpower.com withpower.com/trial/paclitaxel-ramucirumab---zanidatamab-for-gastroesophageal-cancer-99b53

Zanidatamab for Gastroesophageal Cancer These side effects were generally manageable, and the treatment was considered safe and well-tolerated in clinical trials. However, specific safety data for ...