HIV Associated Cancer Clinical Trials

Executive Summary

Clinical trials are considered a better method for treating HIV associated cancer. Most clinical trials are not specific to HIV and cancer patients, and most clinical trials have historically excluded HIV infected patients. This makes it challenging to interpret and apply the treatment to cancer patients infected with HIV. In-depth studies of HIV viral loads among patients, immunodynamics, and cancer biology can only be done in studies specifically designed for clinical trials. The AIDS Malignancy Consortium (AMC) and the National Cancer Institute have teamed up to conduct clinical trials for prioritizing new therapies for approval for novel cancer treatment and provide information about dosage and toxicity to patients infected with HIV so that the prescribed drugs and techniques can be used for the treatment of patients with HIV and cancer. AIDS Malignancy Consortium trial AMC 061 aims to analyze the effects of HAART therapy on patients receiving ritonavir. The Blood and Marrow Transplant Clinical Trials Network 0803/AIDS Malignancy Consortium 071 trial reveal that HIV does not prevent aggressive curative-intent cancer therapy.

Kaposi sarcoma herpesvirus (KSHV) Inflammatory Cytokine Syndrome (KICS) protocols are carried out on patients with KICS. Phase II Study of Dose-Adjusted EPOCH+/-Rituximab in Adults With Untreated Burkitt Lymphoma, c-MYC Positive Diffuse Large B-Cell Lymphoma and Plasmablastic Lymphoma is also another major clinical trial for HIV associated cancer. Phase I Study of MK-3475 (Pembrolizumab) in Patients With Human Immunodeficiency Virus (HIV) and Relapsed/Refractory or Disseminated Malignant Neoplasm is also carried out a clinical trial.

Clinical Trials for HIV Associated Cancer

A clinical trial is a study performed in humans to evaluate medical, surgical, or behavioural interventions. Clinical trials are essential for researchers to determine whether a new treatment, a new drug, medical device or diet, is safe and effective in humans.

New treatments go through several phases in clinical trials. The cancer trials primarily include 4 phases which are conducted for different purposes:

  • Phase 1 trials test whether a new treatment is safe and find out procedures to provide the treatment in the best possible way. Doctors also look for signs that cancer is responding to new treatments.
  • Phase 2 trials look at whether a particular cancer type is responding to the new treatment.
  • Phase 3 trials examine whether a new treatment works better than the conventional treatment.
  • Phase 4 trials examine the detailed information on long-term side effects and benefits and on patients.

Need for AIDS associated cancer clinical trials

Therapeutic advances in cancer treatment are informed through clinical trials. The ability to interpret and apply clinical trial results depends on several factors, including the statistical design of the clinical trial and the selection criteria for the study. Most clinical trials are not specific to HIV and cancer patients, and most clinical trials have historically excluded HIV infected patients. This makes it difficult to interpret and apply the treatment to cancer patients infected with HIV.

The importance of HIV associated cancer clinical trials

Cancer screening tests for patients with HIV and cancer are needed for several reasons. The prognosis, development, and natural history of the disease may differ based on various comorbidities and the patient’s population. There may be concerns about the introduction of specific therapies, such as hematopoietic stem cell transplantation, for people with HIV. There is concern that pharmacokinetic interactions with antiretroviral therapy (ART) may alter the dose-response curve or treatment endpoint of cancer therapy. Cancer drugs may also negatively affect the pharmacokinetics of ART. In-depth studies of HIV viral loads among patients, immunodynamics, and cancer biology can only be done in studies specifically designed to look into these types of problems.

The AIDS Malignancy Consortium (AMC) and the National Cancer Institute have teamed up to conduct clinical trials for prioritizing new therapies for approval for novel cancer treatment, provide information about dosage and toxicity to patients infected with HIV so that the prescribed drugs and techniques can be used for the treatment of patients with HIV and cancer. Below mentioned are a few HIV associated cancer clinical trials.

Name of the Clinical trialClinicalTrials.gov identifierImportant findingsSource
AIDS Malignancy Consortium trial AMC 061NCT00890747Patients receiving ritonavir-based HAART therapy had tolerance to standard doses of sunitinib. Higher toxicity was observed among patients who were treated with ritonavir at a dosage of 37.5 mg/day.Rudex et al., 2014​1​
The Blood and Marrow Transplant Clinical Trials Network 0803/AIDS Malignancy Consortium 071 trialNCT01141712This trial provides compelling evidence that HIV does not prevent aggressive curative-intent cancer therapy and can be used as evidence to include persons with HIV in background clinical trials.Alvarnas et al., 2016​2​
Kaposi sarcoma herpesvirus (KSHV) Inflammatory Cytokine Syndrome (KICS) protocolNCT1419561Patients with KICS demonstrated various types of severe symptoms such as increased KSHV-associated tumours rate, increased mortality, and a unique IL-6/IL-10 signature. KICS may be an important unrecognized factor for increased morbidity and mortality among HIV infected patients.Polizzotto et al., 2016​3​
Phase II Study of Dose-Adjusted EPOCH+/-Rituximab in Adults With Untreated Burkitt Lymphoma, c-MYC Positive Diffuse Large B-Cell Lymphoma and Plasmablastic LymphomaNCT01092182In a multicenter setting, both low-risk and high-risk Burkitt lymphoma patients have exceptional results with 3 and 6 cycles of rituximab therapy respectively. HIV status of patients, risk groups and age, were observed to have no significant effect on the treatment outcome.Dunleavy et al., 2017​4​
Phase I Study of MK-3475 (Pembrolizumab) in Patients With Human Immunodeficiency Virus (HIV) and Relapsed/Refractory or Disseminated Malignant NeoplasmNCT02595866This trial is a phase I clinical trial that looks into the side effects of pembrolizumab among HIV infected patients who had a relapsed malignant neoplasm, who do not respond to treatment or have cancer metastasized in various parts of the body. Immunotherapy using monoclonal antibodies, such as pembrolizumab, may help the immune system of the patient’s body to fight and attack cancer cells, as well as interfere with the growth and proliferation of the tumour cells.Uldrick et al., 2019​5​

References

  1. 1.
    Rudek M, Moore P, Mitsuyasu R, et al. A phase 1/pharmacokinetic study of sunitinib in combination with highly active antiretroviral therapy in human immunodeficiency virus-positive patients with cancer: AIDS Malignancy Consortium trial AMC 061. Cancer. 2014;120(8):1194-1202. doi:10.1002/cncr.28554
  2. 2.
    Alvarnas J, Le R, Wang Y, et al. Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the BMT CTN 0803/AMC 071 trial. Blood. 2016;128(8):1050-1058. doi:10.1182/blood-2015-08-664706
  3. 3.
    Polizzotto M, Uldrick T, Wyvill K, et al. Clinical Features and Outcomes of Patients With Symptomatic Kaposi Sarcoma Herpesvirus (KSHV)-associated Inflammation: Prospective Characterization of KSHV Inflammatory Cytokine Syndrome (KICS). Clin Infect Dis. 2016;62(6):730-738. doi:10.1093/cid/civ996
  4. 4.
    Dunleavy K, Roschewski M, Abramson JS, et al. RISK-ADAPTED THERAPY IN ADULTS WITH BURKITT LYMPHOMA: UPDATED RESULTS OF a MULTICENTER PROSPECTIVE PHASE II STUDY OF DA-EPOCH-R. Hematological Oncology. Published online June 2017:133-134. doi:10.1002/hon.2437_122
  5. 5.
    Uldrick T, Gonçalves P, Abdul-Hay M, et al. Assessment of the Safety of Pembrolizumab in Patients With HIV and Advanced Cancer-A Phase 1 Study. JAMA Oncol. 2019;5(9):1332-1339. doi:10.1001/jamaoncol.2019.2244