Nivolumab + Chemotherapy for Anal Cancer

Not currently recruiting at 679 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Pregnancy, Autoimmune disease, Recent chemotherapy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 4

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding nivolumab, an immunotherapy drug, to standard chemotherapy (carboplatin and paclitaxel) is more effective in treating anal cancer that has spread. Nivolumab helps the immune system fight cancer cells, while chemotherapy stops cancer cell growth. Participants will join one of two groups: one receiving only chemotherapy, and the other receiving both chemotherapy and nivolumab. Individuals with anal cancer that cannot be surgically removed, has recurred, or has spread, and who have not received certain treatments before, might be suitable for this trial. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently on systemic corticosteroids or other immunosuppressive medications, or if you have had recent treatment with another investigational drug.

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

Research shows that nivolumab, combined with the chemotherapy drugs carboplatin and paclitaxel, is generally well-tolerated by patients. In studies, some patients who received nivolumab experienced side effects, but these were often manageable. Common side effects included tiredness and nausea, while serious side effects were less common.

Nivolumab has been used with other cancers and has shown similar safety results. Doctors are familiar with the side effects of carboplatin and paclitaxel, as these chemotherapy drugs are already standard treatments.

Overall, the combination of nivolumab with carboplatin and paclitaxel has proven safe enough to continue studying its effectiveness in treating anal cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for anal cancer?

Researchers are excited about the combination of nivolumab with chemotherapy for anal cancer because it offers a novel approach to treatment. Unlike the standard of care, which typically includes chemotherapy alone, this combination adds nivolumab, an immune checkpoint inhibitor, to the mix. Nivolumab works by unleashing the body's immune system to attack cancer cells more effectively. This dual approach could potentially enhance treatment effectiveness by not only directly targeting the cancer cells with chemotherapy but also boosting the immune system's ability to fight the cancer. This innovative strategy holds promise for improved outcomes in patients with anal cancer.

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

This trial will compare two treatment approaches for advanced anal cancer. Arm A involves treatment with the chemotherapy drugs carboplatin and paclitaxel. Arm B adds nivolumab to this chemotherapy regimen. Research has shown that combining nivolumab with carboplatin and paclitaxel may be promising for treating advanced anal cancer. Studies indicate that nivolumab can enhance the immune system's ability to fight cancer when used with chemotherapy. In earlier research, about 24% of patients treated with nivolumab experienced a reduction in cancer size. Another study found that patients lived for an average of 11.5 months after starting treatment with nivolumab. These findings suggest that adding nivolumab could potentially improve outcomes for people with this type of cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Cathy Eng

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

Adults with metastatic anal squamous cell carcinoma, including those HIV-positive on effective therapy or cured of hepatitis C. Participants must have measurable disease, be in good physical condition (ECOG 0-1), and not pregnant or breastfeeding. Excluded are those with recent major surgery, interstitial lung disease, active infections requiring IV antibiotics, certain autoimmune diseases, or prior systemic chemotherapy for metastatic anal cancer.

Inclusion Criteria

All HIV+ patients should be under the care of an infectious diseases specialist. If a relationship with an infectious diseases specialist is not established, an infectious disease specialist should be consulted. Records of all viral counts and peripheral T-cell counts should be documented in order to follow these values over the course of treatment

All patients must be willing to undergo testing for HIV testing if not tested within the past 12 months

I can understand and am willing to sign the consent form, or I have someone who can do it for me.

Exclusion Criteria

I am using or willing to use effective birth control or abstain from sex as required.

I am not on high-dose steroids or other immune-weakening drugs.

I haven't used chemotherapy or trial drugs for my advanced anal cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive chemotherapy with carboplatin and paclitaxel, with or without nivolumab, every 28 days for up to 6 cycles

24 weeks

3 visits per cycle (in-person)

Extended Treatment

Patients in Arm B may continue receiving nivolumab for up to 2 years in the absence of disease progression or unacceptable toxicity

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

2 years

1 visit at 1 month, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Nivolumab
• Paclitaxel

Trial Overview

This phase 3 trial is testing the effectiveness of adding nivolumab (an immunotherapy drug) to standard chemotherapy drugs carboplatin and paclitaxel in treating metastatic anal cancer. The goal is to see if this combination improves outcomes compared to chemotherapy alone.

How Is the Trial Designed?

Group I: Arm B (carboplatin, paclitaxel, nivolumab) Experimental Treatment 3 Interventions

Patients receive nivolumab IV over 30 minutes on days 1 and 15 of cycle 1 and then on day 1 only of subsequent cycles, paclitaxel IV on days 1, 8, and 15 of each cycle, and carboplatin on day 1 of each cycle. Treatment repeats every 28 days for up to 6 cycles for carboplatin and paclitaxel, and up to 2 years for nivolumab in the absence of disease progression or unacceptable toxicity.

Group II: Arm A (carboplatin, paclitaxel) Active Control 2 Interventions

Patients receive paclitaxel IV on days 1, 8, and 15 of each cycle, and carboplatin IV on day 1 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase II trial involving 51 patients with untreated stage IIIB and IV non-small cell lung cancer, the combination of carboplatin and paclitaxel showed an overall response rate of 27.5%, indicating some effectiveness in treating this aggressive cancer.

The treatment was generally well-tolerated, with modest toxicity levels; only 5% of patients experienced severe nonhematologic side effects, suggesting that this combination therapy could be a safe option for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. Johnson, DH., Paul, DM., Hande, KR., et al.[2015]

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

A phase I trial involving 33 patients tested the combination of cisplatin and carboplatin, revealing that while the combination is feasible, it can lead to unexpectedly severe thrombocytopenia (low platelet count) when using specific doses, particularly 280 mg/m2 carboplatin with 25 mg/m2 cisplatin.

Despite the risk of thrombocytopenia, the combination therapy showed promising responses in tumors known to be responsive to platinum-based treatments, suggesting that further investigation into this combination is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum analogue combination chemotherapy: cisplatin and carboplatin--a phase I trial with pharmacokinetic assessment of the effect of cisplatin administration on carboplatin excretion. Trump, DL., Grem, JL., Tutsch, KD., et al.[2017]

A phase I trial showed that carboplatin and paclitaxel can be safely combined at full doses for treating advanced ovarian cancer, indicating acceptable toxicity levels for patients.

The combination therapy is moving forward to larger randomized trials to compare its effectiveness against cisplatin plus paclitaxel, with specific dosing strategies planned for optimal treatment cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and paclitaxel in ovarian cancer. Ozols, RF.[2015]

In advanced ovarian cancer, the combination of paclitaxel and carboplatin is the standard first-line treatment, showing effectiveness comparable to paclitaxel and cisplatin, while being better tolerated by patients.

For recurrent ovarian cancer, recent trials suggest that paclitaxel/carboplatin may be more effective than single-agent carboplatin, highlighting the importance of ongoing research into new treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced ovarian cancer: a clinical update on first-line treatment, recurrent disease, and new agents. Ozols, RF.[2022]

In a study of patients with advanced non-small cell lung cancer receiving carboplatin and nanoparticle albumin-bound paclitaxel, 55% experienced treatment suspension, primarily due to neutropenia (65.2%) and infections (24.2%).

Baseline liver dysfunction, age 65 or older, and a performance status of 2 were identified as significant risk factors for treatment suspension, highlighting the need for careful monitoring in these patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of risk factors associated with carboplatin and nab-paclitaxel treatment suspension in patients with non-small cell lung cancer. Saito, Y., Takekuma, Y., Shinagawa, N., et al.[2022]

The combination of carboplatin and 3-hour infusional paclitaxel was well-tolerated in a study of 92 women with advanced gynecologic cancers, showing a manageable toxicity profile with neutropenia being the most significant side effect.

In patients with ovarian cancer or primary peritoneal carcinoma, 74% experienced a significant decline in tumor marker levels after treatment, indicating strong antineoplastic activity of this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin plus paclitaxel in the treatment of gynecologic malignancies: the Cleveland Clinic experience. Markman, M., Kennedy, A., Webster, K., et al.[2015]

The combination of paclitaxel and carboplatin showed promising activity in treating endometrial cancer resistant to standard therapies, with 63% of evaluable patients experiencing a significant reduction in tumor size.

While the treatment had acceptable toxicity levels, with some patients experiencing grade 3 or 4 hematologic issues, further follow-up is needed to assess long-term survival outcomes and the overall effectiveness of this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A trial of outpatient paclitaxel and carboplatin for advanced, recurrent, and histologic high-risk endometrial carcinoma: preliminary report. Price, FV., Edwards, RP., Kelley, JL., et al.[2016]

Citations

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Giving nivolumab together with carboplatin and paclitaxel may help doctors find out if the treatment is better or the same as the usual approach. Detailed ...

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Giving nivolumab together with carboplatin and paclitaxel may help doctors find out if the treatment is better or the same as the usual approach. Eligibility ...

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Efficacy and safety of nivolumab in pretreated patients with ...

Overall, median OS was 8.3 months (mo.) (95% CI 4.37-NA) and median PFS was 4.37 mo. (95% CI 3.67-NA). Of note, ORR was ...

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Recent Advances in the Management of Anal Cancer - PMC

The final outcomes from the pooled data of 115 patients from these two studies were encouraging with an objective response rate of 87.7%, and ...

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Advances in anal cancer treatment: current standards, the ...

From the 37 patients treated with nivolumab, 9 had radiographic responses (ORR 24%). Median PFS was 4.1 months, and median OS was 11.5 months.

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pmc.ncbi.nlm.nih.gov/articles/PMC10217754/

Immunotherapy in Anal Cancer - PMC

The longest duration of response was 10.4 months, median progression-free survival (PFS) was 4.1 months, and the median overall survival (OS) ...

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New understandings and research in anal squamous cell ...

This is an open label multicentric study limited to US evaluating the interest of the addition of nivolumab to carboplatin and paclitaxel. The primary end-point ...