Immune System Diseases

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Rare Diseases

Hypersensitivity

Neuroendocrine Tumors

Genital Neoplasms, Female

Biliary Tract Neoplasms

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Urogenital Neoplasms

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Biliary Tract Cancer

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antibodies

Antibodies, Monoclonal

Immune Checkpoint Inhibitors

Immunomodulating Agents

Ipilimumab

Immunoglobulins

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

All Subjects will be treated with: Nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg concurrently every 3 weeks for 4 doses followed by nivolumab only at 480mg every 4 weeks until progression (up to 2 years)

CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) is a key regulator of T cell activity. Ipilimumab is a CTLA-4 immune checkpoint inhibitor that blocks T-cell inhibitory signals induced by the CTLA-4 pathway, increasing the number of tumor reactive T effector cells which mobilize to mount a direct T-cell immune attack against tumor cells. CTLA-4 blockade can also reduce T regulatory cell function, which may lead to an increase in anti-tumor immune response.

A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death-1 (PD-1,PCD-1) with immune checkpoint inhibitory and antineoplastic activities. Nivolumab binds to and blocks the activation of PD-1, an Ig superfamily transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs (antigen presenting cells). This results in the activation of T-cells and cell-mediated immune responses against tumor cells or pathogens. Activated PD-1 negatively regulates T-cell activation and and plays a key role in in tumor evasion from host immunity.

Oliver Klein, MD

Jonathan Cebon, MD

The four tumour streams that will be studied in this protocol are based on immunotherapy sensitive rare cancers from CA209-538 which will be further investigated under this protocol and divided into four groups:

1. Neuroendocrine cancers: Atypical bronchial carcinoid, neuroendocrine carcinoma and Grade 3 NETs independent of primary site (SCLC excluded)
2. Biliary tract cancers: Intrahepatic cholangiocarcinoma and gallbladder carcinoma
3. Gynaecological malignancies: Ovarian clear cell carcinoma, uterine clear cell carcinoma, uterine/ovarian carcinosarcoma, uterine leiomyosarcoma and vaginal/vulva squamous cell carcinoma
4. Mismatch repair protein deficient (MSI-H) cancers (excluding colorectal carcinoma).

The role of immunotherapy is being defined in more common cancer types, however because of their rarity, the efficacy of immunotherapy for these cancers is poorly defined.

This protocol provides an important opportunity to establish whether the combination of nivolumab \& ipilimumab has efficacy in these cancers.

This is a phase 2 clinical trial of nivolumab combined with ipilimumab in immunotherapy sensitive rare cancers. This study will allow an evaluation of the clinical benefit, as measured by progression free survival (PFS) \>6 months and overall survival (OS), provided by nivolumab combined with ipilimumab.

Study Rationale Clinically advanced rare cancers pose a significant clinical challenge because evidence based treatments are seldom available for patients suffering from these malignancies. Despite little evidence that shows clinical benefit, these patients are often treated with chemotherapeutic agents that are used in patients with more common malignancies that arise from the same anatomical site. Furthermore, because of small numbers, patients are often excluded from clinical trials with newer agents. CA209-538 examined this treatment combination in three 'baskets' of rare cancers: rare upper gastrointestinal, gynaecological and neuroendocrine cancers. The cancers on study all individually had an incidence of \<2/100000/year. The cancer specific survival of patients diagnosed with a rare malignancy is significantly lower than with common cancers highlighting the need to improve management and treatment of rare cancer patients. Given the success of cancer immunotherapy with checkpoint regulators such as ipilimumab and nivolumab in a range of different cancer types, it was postulated that these agents could be beneficial in rare cancers and improve the overall outlook of patients with these conditions. CA209-538 enrolled 120 rare cancer patients on study, clinical benefit rate was \>30% across all baskets, long term survival follow-up is underway.

This study will enrol 240 participants, across 4 cohorts with histotypes which demonstrated clinical benefit on CA209-538. All participants will receive ipilimumab and nivolumab as combination immunotherapy.

This is an open label study, all patients receive the same treatment as per the protocol.

Combination Immunotherapy in Rare Cancers Under InvesTigation

Ipilimumab and Nivolumab Combination Therapy in Patients With Selected Immunotherapy Sensitive Advanced Rare Cancers

No plan to share individual participant data

Clinical benefit rate for whole population (CR (complete response)+PR (partial response) assessed by radiographic evidence in accordance with RECIST 1.1 criteria

Progression-free survival based on clinical or radiographic evidence of progressive disease according to RECIST 1.1 criteria at 6 months.

Quantification of treatment related toxicities according to CTCAE V5.0.

Bristol-Myers Squibb

Olivia Newton-John Cancer Research Institute

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Gland and Hormone Related Diseases

Carcinoma

Respiratory Aspiration

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Uterine Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Endocrine System Diseases

Gonadal Disorders

Uterine Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Participants receive a self-directed 20-minute eMMB video and are instructed to practice eMMB at least once before surgery and daily for 2 weeks after surgery. Participants may also request additional guidance from a yoga instructor via telephone and video conference before surgery and again 1 day after surgery or as soon as feasible.

Questionnaire Administration

Undergo eHealth mindful moving and breathing

Supportive Care

Stephanie Sohl

This trial determines how well eHealth mindful movement and breathing works to improve outcomes in participants undergoing gynecologic surgery. Supportive therapy, such as eHealth mindful movement and breathing, uses techniques that include gentle movements, breathing, and relaxation techniques which may help participants cope with and improve their surgical experiences.

PRIMARY OBJECTIVES:

I. To field-test implementation strategies of the mindful movement and breathing (eMMB) intervention that has been adapted to the eHealth Format.

OUTLINE:

Participants receive a self-directed 20-minute eMMB video and are instructed to practice eMMB at least once before surgery and daily for 2 weeks after surgery. Participants may also request additional guidance from a yoga instructor via telephone and video conference before surgery and again 1 day after surgery or as soon as feasible.

After completion of study, participants are followed up at 4 weeks from surgery.

EHealth Mindful Movement and Breathing in Improving Outcomes in Participants Undergoing Gynecologic Surgery

EHealth Mindful Movement and Breathing to Improve Gynecologic Cancer Surgery Outcomes: Aim II

This is a feasibility study to iteratively refine the eMMB implementation strategies with 10-15 consecutive participants enrolled. Participants will be asked to complete a brief usability questionnaire about their confidence in their ability to complete the intervention. The number of participants will depend on when a consensus is reached on a manual for implementing interventions and will be determined by calculating 95% confidence intervals around all the secondary outcomes.

Participants who were recruited and agreed to participate in the Mindful Movement and Breathing (eMMB) sessions and those who completed all assessments will be computed.

To be determined by comparing participants who were adherent to attending study visits and interventions by an adherence assessment (1) Completion of the videoconference session; (2) any additional contact with the interventionists; (3) use of the self-directed intervention:

Adverse events will be reported upon occurrence monthly. Specifically, they will be labeled definitely unrelated, definitely related, probably related, or possibly related to the study intervention.

To be assessed by calculating the percent of participants who complete the 4-week visit.

National Cancer Institute (NCI)

Wake Forest University Health Sciences

Participants receive a self-directed 20-minute eMMB video and are instructed to practice eMMB at least once before surgery and daily for 2 weeks after surgery. Participants may also request additional guidance from a yoga instructor via telephone and video conference before surgery and again 1 day after surgery or as soon as feasible.

Questionnaire Administration: Receive questionnaire

Supportive Care: Undergo eHealth mindful moving and breathing

Supportive Care (eMMB)

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Meg O'Mara - Study Coordinator

Number of Participants Confident in the Use of EHealth Format

Number of Participants Recruited and Completed All Assessments

Number of Participants That Adhered to Study Interventions

Number of Participants Reporting Adverse Events

Percentage of Participants Completing 4-week Visits

Overall Study

Skin and Connective Tissue Diseases

Blood and Lymph Conditions

Heart and Blood Diseases

Colorectal Neoplasms

Breast Neoplasms

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Infertility

Breast Diseases

Skin Diseases

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Lymphosarcoma

Participants receive standard of care including education materials about fertility preservation from the Livestrong organization and a referral for fertility preservation, if requested.

Participants receive standard of care as in Arm I. Participants also use the decision-making the website.

Best Practice

Educational Intervention

Internet-Based Intervention

Terri L Woodard

This trial studies how well a decision aid website works in helping to make decisions about fertility in participants with cancer. Decision aid websites that provide information about fertility preservation (maintaining your ability to have children of your own after cancer treatment) may help participants with cancer make fertility-preservation decisions.

PRIMARY OBJECTIVES:

I. To assess the effect of the Pathways to Fertility patient decision aid website (DA website) with women of reproductive age seen at the MD Anderson Oncofertility Service, in terms of improving patients' decisional conflict. (Part 1) II. To assess the effect of a multicomponent oncofertility decision support intervention (multicomponent DS intervention) compared to usual care with women of reproductive age at selected MD Anderson Houston Area Locations (HALs) on patients' decisional conflict. (Part 2)

SECONDARY OBJECTIVES:

I. To assess patients' decision-making process (e.g., preparation for decision making, decision self-efficacy, satisfaction) and decision quality (e.g., fertility preservation knowledge, clarity of patients' values, and congruence of preferences with the decision and/or treatment received). (Part 1) II. To assess patients' decision-making process (e.g., preparation for decision making, decision self-efficacy, satisfaction) and decision quality (e.g., fertility preservation knowledge, clarity of patients' values, and congruence of preferences with the decision about whether to accept fertility preservation referral and/or fertility preservation treatment). (Part 2)

EXPLORATORY OBJECTIVES:

I. To explore the acceptability of the DA website (e.g., length, clarity, ease of use) and feasibility of the research methods (e.g., preferences for viewing at home versus at the clinic, timing of viewing, website usage, recommendations for improvement), in preparation for future planned dissemination and implementation studies. (Part 1) II. To explore the feasibility of the multicomponent DS intervention and research methods (e.g., clinician's perspectives of the educational session and referral process, website usage, rates of referrals, recommendations for improving the intervention and referral process) as delivered in the HALs oncology clinics, in preparation for future planned dissemination and implementation studies. (Part 2)

OUTLINE:

PART 1: Participants review decision aid website and complete questionnaires to help researchers learn the website's effect.

PART 2: Participants are randomized into 1 of 2 arms.

ARM I: Participants receive standard of care including education materials about fertility preservation from the Livestrong organization and a referral for fertility preservation, if requested.

ARM II: Participants receive standard of care as in Arm I. Participants also use the decision-making the website.

Decision Aid Website in Helping to Make Decisions About Fertility in Participants With Cancer

Patient-Centered Decision Counseling for Women at Risk of Cancer-Related Infertility: Efficacy Study and Comparative-Effectiveness Randomized Trial

Will explore the acceptability of the DA website (e.g., length, clarity, ease of use) and feasibility of the research methods (e.g., preferences for viewing at home versus at the clinic, timing of viewing, website usage, recommendations for improvement), in preparation for future planned dissemination and implementation studies.

Will explore the feasibility of the multicomponent DS intervention and research methods (e.g., clinician's perspectives of the educational session and referral process, website usage, rates of referrals, recommendations for improving the intervention and referral process) as delivered in the HALs oncology clinics, in preparation for future planned dissemination and implementation studies.

Will assess the effect of the Pathways to Fertility patient decision aid website (DA website) with women of reproductive age seen at the MD Anderson Oncofertility Service, in terms of improving patients' decisional conflict.

Will assess the effect of a multicomponent oncofertility decision support intervention (multicomponent DS intervention) compared to usual care with women of reproductive age at selected MD Anderson Houston Area Locations (HALs) on patients' decisional conflict.

Will assess patients' decision-making process (e.g., preparation for decision making, decision self-efficacy, satisfaction) and decision quality (e.g., fertility preservation knowledge, clarity of patients' values, and congruence of preferences with the decision and/or treatment received).

Will assess patients' decision-making process (e.g., preparation for decision making, decision self-efficacy, satisfaction) and decision quality (e.g., fertility preservation knowledge, clarity of patients' values, and congruence of preferences with the decision about whether to accept fertility preservation referral and/or fertility preservation treatment).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Combination Immunotherapy in Rare Cancers Under InvesTigation	NCT04969887	Advanced Biliar... Neuroendocrine ... Female Reproduc... MSI-H Solid Mal...	Ipilimumab Nivolumab	18 Years -	Olivia Newton-John Cancer Research Institute
EHealth Mindful Movement and Breathing in Improving Outcomes in Participants Undergoing Gynecologic Surgery	NCT03379376	Female Reproduc... Malignant Femal... Malignant Uteri... Ovarian Carcino... Ovarian Neoplas... Suspicious for ... Uterine Neoplas...	Questionnaire A... Supportive Care	18 Years -	Wake Forest University Health Sciences
Decision Aid Website in Helping to Make Decisions About Fertility in Participants With Cancer	NCT03141437	Breast Neoplasm Colorectal Neop... Female Reproduc... Health Care Pro... Lymphoma Plasma Cell Mye...	Best Practice Educational Int... Internet-Based ... Questionnaire A...	18 Years - 45 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for female reproductive system neoplasm