Nivolumab + Chemotherapy for Anal Cancer

Recruiting at 659 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

205 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether adding nivolumab to standard chemotherapy is more effective for patients with metastatic anal cancer. Nivolumab helps the immune system fight cancer, while chemotherapy kills or stops cancer cells from growing. Nivolumab has shown significant effectiveness in treating metastatic squamous cell carcinoma of the anal canal.

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.

What data supports the effectiveness of the drug combination Nivolumab, Carboplatin, and Paclitaxel for anal cancer?

Research shows that the combination of Carboplatin and Paclitaxel has been effective in treating other types of cancer, such as ovarian and lung cancer, with significant tumor reduction and manageable side effects. This suggests potential effectiveness for anal cancer as well. ^{1 2 3 4 5}

Is the combination of Nivolumab, Carboplatin, and Paclitaxel generally safe for humans?

The combination of Carboplatin and Paclitaxel has been studied in various cancers and is generally considered safe, though it can cause side effects like myelosuppression (lowered blood cell counts) and neuropathy (nerve damage). These side effects are usually manageable, and the treatment is often continued with dose adjustments if needed. ^{6 7 8 9 10}

How is the drug combination of Nivolumab, Carboplatin, and Paclitaxel unique for treating anal cancer?

This drug combination is unique because it includes Nivolumab, an immunotherapy drug that helps the immune system fight cancer, alongside Carboplatin and Paclitaxel, which are chemotherapy drugs. While Carboplatin and Paclitaxel are commonly used in other cancers, the addition of Nivolumab may offer a novel approach by potentially enhancing the body's immune response against anal cancer. ^{1 2 3 5 11}

Research Team

Cathy Eng

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Treatment of ovarian cancer: current status. [2015]

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

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

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

Phase II study of sequential doublets: topotecan and carboplatin, followed by paclitaxel and carboplatin, in patients with newly diagnosed advanced ovarian cancer. [2015]

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

A trial of outpatient paclitaxel and carboplatin for advanced, recurrent, and histologic high-risk endometrial carcinoma: preliminary report. [2016]

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

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. [2015]

6. United States 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. [2017]

7. Germany 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. [2022]

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

Carboplatin and paclitaxel in ovarian cancer. [2015]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Feasibility and toxicity of weekly Paclitaxel-Carboplatin in 131 patients with pretreated and non-pretreated solid tumors. [2022]

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

Carboplatin plus paclitaxel in the treatment of gynecologic malignancies: the Cleveland Clinic experience. [2015]

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

Taxane/platinum/anthracycline combination therapy in advanced epithelial ovarian cancer. [2015]