Paclitaxel + Ramucirumab +/- Zanidatamab for Gastroesophageal Cancer

Recruiting at 20 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

Trial Summary

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.

What data supports the effectiveness of the drug combination of Paclitaxel, Ramucirumab, and Zanidatamab for treating gastroesophageal cancer?

Research shows that combining ramucirumab with paclitaxel improves survival and delays disease progression in patients with advanced gastric or gastroesophageal cancer compared to paclitaxel alone. This suggests that adding ramucirumab to paclitaxel is effective, and the combination may be further enhanced with zanidatamab. ^{1 2 3 4 5}

Is the combination of Paclitaxel, Ramucirumab, and Zanidatamab safe for treating gastroesophageal cancer?

Paclitaxel and Ramucirumab have been studied together for treating advanced gastric and gastroesophageal cancer, showing common side effects like high blood pressure, fatigue, and diarrhea. These side effects were generally manageable, and the treatment was considered safe and well-tolerated in clinical trials. However, specific safety data for Zanidatamab in this combination is not provided in the available research. ^{2 4 6 7 8}

What makes the drug combination of Paclitaxel, Ramucirumab, and Zanidatamab unique for gastroesophageal cancer?

This drug combination is unique because it adds Zanidatamab, a novel agent, to the standard second-line treatment of Paclitaxel and Ramucirumab, which are already known to improve survival in advanced gastroesophageal cancer. Zanidatamab targets specific proteins on cancer cells, potentially enhancing the effectiveness of the existing treatment. ^{2 4 6 9 10}

What is the purpose of this trial?

This study is being done to answer the following question: Can the chance of gastroesophageal cancer growing or spreading be lowered by adding a drug called zanidatamab to the usual combination of drugs? We are doing this study because we want to find out if this approach is better or worse than the usual approach for this type of cancer. The usual approach is defined as care most people get for gastroesophageal cancer

Research Team

Elena Elimova

Principal Investigator

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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 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 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]

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]

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 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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Outcomes of Ramucirumab Plus Paclitaxel Among Patients With Previously Treated Metastatic Gastric/Lower Esophageal Cancer: A Real-world Study. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Ramucirumab: A Review in Advanced Gastric Cancer. [2023]

3. England 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. [2023]

4. England 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. [2023]

5. England 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. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Ramucirumab for Gastric Cancer. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Optimizing treatment duration with ramucirumab and paclitaxel by managing chemotherapy-associated toxicity: Review of four cases. [2020]

8. England 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. [2023]

9. England 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). [2022]

10. France pubmed.ncbi.nlm.nih.gov

Ramucirumab as Second-Line Therapy in Metastatic Gastric Cancer: Real-World Data from the RAMoss Study. [2023]